Anti Infective Guideline 2012

UNIVERSITI KEBANGSAAN Malaysia National University of Malaysia

PPUKM ANTI-INFECTIVE GUIDELINE 2012

All Rights Reserved. The authors, editor have every effort to provide accurate information at time of printing.The information in this book makes no warranty, express or implied, with respect to accuracy or completeness of contents of the publication.Application of information remains the professional responsibility of the practititoner. ACKNOWLEDGEMENT

This guideline would not exist without the hard work from the Development Group who revised, checked, discuss, debated, designed, typed and reviewed as a team. We would like to thank the whole team for their eﬀort and continuous commitment to help develop this Guideline.

ANTI-INFECTIVE GUIDELINE DEVELOPMENT GROUP 2011/2012

Y.Bhg. Prof. Dato’ Dr. Raymond Azman Ali Dean of Facuty of Medicine Director of UKM Medical Centre

Members of the Drugs and Therapeutics Committee

Prof Dr Jaafar Hj Md Zain Dato’ Dr Noorimi Hj Morad (Chairman) Chief Operations Oﬃcer, PPUKM Consultant Specialist Anesthesia and Intensive Care Deputy Dean of Clinical Services

Prof Dr S Fadilah Abdul Wahid Prof (K) Dr. Abd. Hamid Abd Rahman Consultant Haematologist Consultant Psychiatrist Head, Department of Medicine & Cell Therapy Center

Prof. Madya (K) Dr. Oteh Maskon Prof Madya Dr Razman Jarmin Consultant Cardiologist Consultant Specialist, Hepatobiliary Head, Cardiology Department Surgeon Head, Surgery Department

Prof Dr Mohd Hashim Omar Prof Madya (Klinikal) Dato’ Dr Fuad Ismail Senior Consultant, Obstetric and Consultant Oncologist Gynaecologist Head, Oncology Department

Dr Petrick Periyasamy (Advisor) Puan Faridah Md Yusof (Advisor) Specialist, Infectious Diseases Chief Pharmacist Head, Infectious Disease Unit

Head of Department/ Head of Unit

Prof Madya Dr Jegan Thanabalan Mr Muhammad Ishamuddin Consultant Neurosurgeon Bin Ismail Specialist, Cardiothoracic Surgeon

iii Mr Badrulhisham Bin Bahadzor Dr Tzar Mohd Nizam bin Khaithir Consultant Urologist Clinical Microbiologist

Dr Ramliza bt Ramli Dr Faizal Amri Hamzah Clinical Microbiologist Specialist, Emergency Medicine

Prof Dr Cheah Fook Choe Dr Kamal Bashar Abu Bakar Professor of Paediatrics Specialist, Anaesthesiology (Neonatology) and Senior Consultant Neonatologist

Dr Esa Kamaruzaman Dr. Mushawiahti bt Mustapha Specialist, Anesthesiology Specialist, Ophthalmology

Dr. Mohd Nazimi Abd. Jabar Dr Noor Zetti Zainol Rashid Specialist, Oral & Maxillofacial Clinical Microbiologist Surgery

Prof Madya Dr Abd Halim Abd Prof Dr Khairani Omar Rashid Consultant Specialist, Specialist, Orthopaedic Family Medicine and Adolescent Health

Prof (K) Dr Abdullah Sani bin Prof Madya Dr. Abdul Halim Abdul Gafor Mohamed Consultant Nephrologist Consultant Otorhinolarnyngologist Head, Nephrology unit Head and Neck Surgeon

Professor Dr Roslina A Manap Prof Madya Dr Sheikh Anwar Abdullah Senior Consultant, Respiratory Consultant Gastroenterologist Medicine Head, Respiratory Head, Gastroenterology Unit Unit

Prof. Madya Dr. Fauzi Md. Anshar Dr Shahrul Azmin Md. Rani Consultant, Respiratory Medicine Specialist, Neurology Respiratory Unit Neurology Unit

Dr Suehazlyn Zainudin Dr Adawiyah Jamil Specialist, Endocrinology Specialist, Dermatology Head, Dermatology Unit

Dr Farah Naaz Momtaz Ahmad Puan Khatijah Moidutty Specialist, Family Medicine Head, Nursing Department Primer Medical Centre

Puan Rabaiah Hj Arham Head, Finance Department

iv Jabatan Farmasi (Urusetia)

Mr Dexter Van Dort Ms Birinder Kaur Deputy Manager of Pharmacy Pharmacist Head of Out-Patient Unit Head of Sterile Unit

Puan Shariﬀah Norasmah Ms Lau Chee Lan In-patient Pharmacist Clinical Pharmacist (Critical Care & Head of In-Patient Unit Infectious Disease) Head of Clinical Unit

Ms Pau Kiew Bing Ms Kong Shue Hong Clinical Pharmacist Clinical Pharmacist Nephrology Cardiology

Ms Lysia Loong Ms Evelyn Ho Jia Wen Clinical Pharmacist Clinical Pharmacist Hematology Internal Medicine

Mr Ong Aik Liang Ms Ivy Mok Pooi Wan Pharmacist Pharmacist In-patient Department Retail Pharmacy

Ms Sarah Anne Roberts Ms Farah Waheeda Clinical Pharmacist Clinical Pharmacy Internal Medicine Internal Medicine

Ms Izyan Diyana Ibrahim (Editor) Pn Michelle Tan Hwee Pheng (Editor) Drug Information Pharmacist Drug Information Pharmacist Head, Drug Information Unit

v TABLE OF CONTENTS

Foreword from the Chairman Foreword from the Infectious Disease Specialist Acknowledgement Abbreviations

Chapter 1a. Recommended Treatment- Different Site : Medical infections Cardiovascular Infections CNS Infection EENT Infections (Eye, Ear, Nose, Throat) Febrile neutropenia patients Gastrointestinal Infections Genitourinary Tract & Gynaecological Infections Intravascular Catheter-Related Infection Odontogenic Infections Respiratory Tract Infection Sexually Transmitted Diseases (STDs) Chapter 1b. Recommended Treatment- Different Site : Surgical and Orthopedic infections Bone & Joint Infections Skin & Soft Tissue Infections Vascular Chapter 1c. Recommended Treatment- Different Site : Tropical Infection

Chapter 2. Recommended Agents based on selected Organisms Recommended antimicrobial agents Recommended antifungal agents Comparison of antimicrobial spectra among common clinical isolates

Chapter 3a. Treatment of HIV infections Chapter 3b. Viral infections Chapter 3c. Mycobacterial infections Chapter 3d. Parasite infections Chapter 3e. Treatment of fungal, actinomycotic and nocardial infections

vi Chapter 4. Opportunistic infections in immunocompromised patients

Chapter 5a. Surgical antibiotic prophylaxis Chapter 5b. Bacterial endocarditis prophylaxis Chapter 5c. Medical prophylaxis Post Exposure Prophylaxis

Chapter 6a Travel vaccines Chapter 6b Vaccines in PPUKM

Appendix A : Needle prick injury Appendix B : Therapeutic Drug Monitoring Sampling Guideline

vii A word from the Chairman…

Antimicrobial resistance is increasingly becoming a threat in our society. It causes increased morbidity, mortality and health care costs. The widespread resistance of anti-infectives are rapidly increasing whereas the development of newer anti-infectives are not able to cope with the rate of resistance. Therefore it is very crucial that we ensure judicious use of anti-infectives to control antimicrobial resistance. This update of the PPUKM Anti-infective guideline has been developed by the Anti-Infective Review Panel which consists of Drugs and Therapeutics Committee, Infectious Disease Consultant, Head of Departments, Head of Units, Microbiologists and Pharmacists. These guidelines have been updated based on evidence based reference and a thorough inter-disciplinary discussion session. As a result of this Anti-Infective Review meeting, the Antibiotic Stewardship Activity by Dr Petrick and Clinical Pharmacists has been initiated to promote the appropriate use of medications by ensuring optimal selection, dose and duration of antibiotic used. It is hoped that this Anti-Infective Guideline will be widely used and enforced by all levels of Health Care Profes- sionals to promote rasional use of antibiotics with better application of clinical knowledge and better adherence to good practice. Lastly, I would like to commend the Infectious Disease Consultant Dr Petrick and the Review Panel for their hard work and eﬀort in updating the guideline for the PPUKM healthcare community.

Prof Dr Jaafar Hj Md Zain Drugs and Therapeutics Committee Chairman Deputy Dean of Clinical Services A word from Our Infectious Disease Specialist

I would like to take this opportunity to introduce this new edition of the PPUKM Anti-Infective Guidelines. This edition sees some new and exciting changes done to the format and the content to make it more user friendly especially to the junior doctors.

There are some new exciting chapters which have been added and all the chapters have been updated to reﬂect the current time. Some of the signiﬁcant changes made in this edition were division of chapters on treatment according to site of infections for easy search. Other new exciting chapters added are vaccines and management of post exposure prophylaxis for needle stick injury in PPUKM

The local strain of bacteria that infects our patients and their sensitivity (popularly called as local data) are presented clearly so that we can have a better understanding on what empirical antibiotics to use for our patients. It is also hoped that all of us will be prudent with the choices of antibiotics we make in order to reduce the occurrence of multidrug resistant organisms in our patients.

This guideline was reviewed by relevant specialists and checked with other international and national guidelines. I take this opportunity to thank all the various people who have come together and worked hard to update the guidelines.

Finally, this endeavour would not be possible without the tremendous sacriﬁces done by all of our hard working colleagues from the Pharmacy Department from organizing everything up to the ﬁnal editing. I salute you!

Last but not least, we hope that all this eﬀort will not be in vain and the end users (you and me) will ﬁnd this edition extremely useful for our day to day management of infections.

It is truly a guideline by the ‘people’ for the ‘people’.

Dr Petrick Periyasamy

ix Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment according to DIFFERENT SITE CARDIOVASCULAR INFECTIONS Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Infective Endocarditis Native valve Benzylpenicillin (Pen G) Vancomycin 15mg/kg q For IVDU: Empirical therapy (before culture results) 3MU q4h IV x 4wks 12h IV x 4wks Cloxacillin 2g q4h IV x 4wks + + + Viridan strep (35%) Gentamicin 1mg/kg q8h IV Gentamicin 1mg/kg q 8h IV Gentamicin 1mg/kg q8h IV 'other' strep (20%,) x 2wks x 2wks x 2wks enterococci (15%) Change antibiotic when culture result become available. staphylocci (30%) 1 Mega Unit =0.6 grams Penicillin G

Native Valve: Culture +ve S. viridans, S. bovis (Pen G MIC 0.1ug/ml) Benzylpenicillin (Pen G) Benzylpenicillin (Pen G) In penicillin hypersensitivity, use 3MU q4h IV x 4 wks 3MU q4h IV Ceftriaxone 2g q24h IV x 4wks x 2wks + Gentamicin 1mg/kg q8h IV x 2 wks S. viridans, S. bovis (Pen G MIC > 0.1 to < 0.5ug/ml) Benzylpenicillin (Pen G) 3 Vancomycin 15mg/kg q12h MU q4h IV x 4 wks IV x 4wks + OR Gentamicin 1mg/kg q8h IV Teicoplanin 400 mg q12h x 2 wks for 3 doses then 400 mg q24h IV x 4wks

1 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Maintenance : Isoniazid 15 mg/kg twice weekly + Rifampicin 10 mg/kg twice weekly x 10 mth

No neurological deﬁcit and CSF Culture Induction : Ampho B (0.7–1.0 mg/kg per day IV) Negative at 2 weeks + Flucytosine (100mg/kg per day orally in 4 divided doses) for 4 weeks . Consodilation : Fluconazole 400 mg od for 8 weeks Maintenance: Fluconazole 200 mg od for 6–12 months Neurological complications and Induction : CSF Culture still Positive at 2 weeks Ampho B (0.7–1.0 mg/kg per day IV) + Flucytosine (100mg/kg per day orally in 4 divided doses) for 6 weeks . Consodilation : Fluconazole 400 mg per day for 8 weeks Maintenance: Fluconazole 200 mg od for 6–12 months If ﬂucytosine is not given or treatment is interrupted, consider lengthening conventional Ampho B or Liposomal AmB induction therapy for at least 2 weeks 10 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative + Gentamicin 1mg/kg q8h IV x 2 wks S. viridans, S. bovis, (Pen G MIC 1.0ug/ml) Pen G 4 MU q4h IV x 4-6 Vancomycin 15mg/kg q12h wks x 4-6 wks + OR Gentamicin 1mg/kg q8h IV Teicoplanin 400 mg q12h x 4-6 wks for 3 doses then 400 mg q24h IV x 4-6 wks + Gentamicin 1mg/kg q8h IV x 4-6 wks Enterococci with no high-level Gentamicin Ampicillin 2 g q 4h IV x 4-6 Vancomycin 15mg/kg q12h resistance wks x 4-6 wks + OR Gentamicin 1mg/kg q8h IV Teicoplanin 400 mg q12h x 4-6 wks for 3 doses then 400 mg q24h IV x 4-6 wks + Gentamicin 1mg/kg q8h IV x 4-6 wks Enterococci (MIC Gentamicin > 500-2000ug/ml) - Ampicillin 2 g q4h IV x 4-6 Vancomycin 15mg/kg q12h Cure rate 50%: consider surgical high level resistance wks IV x 4-6wks + OR removal of infected valve in Streptomycin 15mg/kg in 2 Teicoplanin 400 mg q12h failure. 2 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

equally divided doses IV/IM + x 4-6 wks Streptomycin 15mg/kg in 2 equally divided doses IV/IM x 4-6 wks

Staph aureus: MSSA (methicillin – sensitive) Cloxacillin 2 g q4h IV x 4-6 Vancomycin 15mg/kg q12h Most IVDU will fall into this wks + Gentamicin 1mg/kg IV category. q8h IV x 3-5 days OR Teicoplanin 400mg q12h for Total therapy for 6 weeks. 3 doses then 400mg q24h Then Cloxacillin 500 mg q6h + Fusidic Acid 500 mg q8h Staph. Aureus: MRSA (methicillin – Vancomycin 15mg/kg q12h Teicoplanin 400 mg q12h resistant) IV x 4-6 wks for 3 doses then 400 mg q24h IV x 4-6 wks Pseudomonas aeruginosa Amikacin 15mg/kg q24h IV Duration of treatment of at least 6 + weeks Pip/Tazo 4.5g q8h IV OR Ceftazidime 2g q8h IV OR Cefepime 2g q8h IV 3 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Native Valve: Culture – ve

HACEK group Ampicillin 2 g q4h IV x 4wks Ceftriaxone 2g q24h IV x HACEK (acronym for H. parainﬂuen- + 4 wks zae, H. aphrophilis, Actinobacillus, Gentamicin 1mg/kg q8h IV x Cardiobacteruim, Eikenella, Kingella) 4 wks

Q fever, psittacosis, brucellosis, bartonella Emphasis is on diagnosis AJM 1996; 100: 629. For Bartonella, refer Circulation 2005:111;394-434

Prosthetic valve

S. epidermidis, S. aureus, Vancomycin 15mg/kg q12h Teicoplanin 400 mg q12h Early surgical consultation advisable. Enterobacteriaceae, diphtheroids, fungi (rare) IV for 3 doses then 400 mg + q24h IV Change to appropriate antibiotics Gentamicin 1mg/kg q8h IV + when culture results available. Rifampicin 4 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment according to DIFFERENT SITE CENTRAL NERVOUS SYSTEM Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Brain Abscess Primary Ceftriaxone 2 g q12h IV Benzylpenicillin 4 MU q4h Surgical drainage if: Streptococci (60-70%), + IV + - size > 2.5cm Bacteroides (20-40%), Metronidazole 500mg q8h Metronidazole 500mg q8h - neurological deterioration IV x 6 wks IV x 6 wks Enterobacteriaceae (25-33%), S. aureus (10-50%) Valve: Culture +ve Post-surgical, post-trauma Cloxacillin 2 g q4h IV + Meropenem 2 g q8h IV + Use Vancomycin for suspected/ S. aureus, Enterobacteriaceae Ceftazidime 2 g q8h IV Cloxacillin 2 g q4h IV proven MRSA.

Encephalitis

Herpes simplex, arboviruses, rabies, rarely Acyclovir 10 mg/kg (infuse over 1h) q8h IV 14 - 21 days listeriosis (assume HSV-1 until exclusion) Acute Meningitis (Aseptic- Pleocytosis of 100cells, CSF normal glucose, no organism on gram stain and/or culture)

Benzylpenicillin 5MU q6h Leptospirosis IV OR 5 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Ampicillin 0.5 – 1 g q6h IV OR Doxycycline 100 mg q12h po HSV (2) and VZV Meningitis (severe cases) Acyclovir 10 mg/kg q8hIV x 10 – 14 days

Acute Meningitis (Septic) Goal is CSF exam in 30 min. and then empiric therapy. If focal neurologic deficit, give empiric therapy, do CT brain, then do LP. 1) CSF Gram stain negative Ceftriaxone 2 g q12h IV Meropenem 2 g q8h IV Ceftriaxone may be changed to OR q24hr after 48 hours if patient has Cefotaxime 2 g q12h IV responded well Child-Adult < 50 yrs old + S. pneumo, meningococci, Dexamethasone 0.15 mg/kg Treat for 10 – 14 days. H. influenzae q6h IV x 2-4d with or just before antibiotic Dexamethasone : 1st dose 15 -20 min before first antibiotic given. > 50 yrs, alcoholism and other debilitating disease Ceftriaxone 2 g q12h IV Meropenem 2 g q8h IV To change to Ampicillin 2 g q6h IV if OR + Listeria is a pathogen. Cefotaxime 1 g q12h IV Dexamethasone 0.15mg/kg S. pneumo, listeria, Gram–negative bacilli + q6h IV x 2-4d with or just Dexamethasone 0.15mg/kg before antibiotic q6h IV x 2-4d with or just before antibiotic 6 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Any age with impaired cellular immunity Ampicillin 2 g q4h IV Meropenem 1 g q8h IV Listeria, Gram-neg. baccilli + Ceftriaxone 2 g q12h IV

Post neurosurgery or post-head-trauma Cloxacillin 2 g q6h IV Give Vancomycin 1 g q8h IV if MRSA + suspected / proven S. pneumo (most common if CFS leak), Cefepime 2g tds IV S. aureus, coliforms, P. aeruginosa 7 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment according to DIFFERENT SITE CENTRAL NERVOUS SYSTEM Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Infected ventriculo-peritoneal shunt Cloxacillin 2 g q4h IV Cloxacillin 2 g q4h IV Early shunt removal usually (for any age group) + + necessary. Cefepime 2g tds IV Sulperazone 2 g q12h IV S. epidermidis, S. aureus, coliforms, diphtheroids Give Vancomycin 1 g q8h IV if MRSA suspected / proven 2) CSF Gram stain positive, Ceftriaxone 2 g q12h IV Meropenem 2 g q8h IV Treat for 10-14 days OR immuno-competent Cefotaxime 2g q4-6h IV Gram +ve cocci S. pneumonia + Dexamethasone 0.15 mg/kg q6h IV x 2-4 days with or just before antibiotic

Gram -ve cocci Ceftriaxone 2 g q12h IV Benzylpenicillin (Pen G) 4 Treat for 7 days. N. meningitidis OR MU q4h IV OR Dexamethasone : 1st dose to be Cefotaxime 2 g q4-6h IV Ampicillin 2 g q4h IV given 15-20 minutes before 1st + Dexamethasone antibiotic given. 0.15mg/kg q6h IV x 2-4 days with or just before antibiotic 8 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment according to DIFFERENT SITE CENTRAL NERVOUS SYSTEM Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Gram -ve bacilli Ceftazidime 2 g q8h IV Meropenem 2 g q8h IV Treat for 14 - 21 days H. inﬂuenza, coliforms, P. aeruginosa OR OR Cefepime 2 g q8h IV Ciproﬂoxacin 400 mg q8-12h IV

Primary Amoebic Amphothericin B Meningoencephalitis 1mg/kg/day Free living amoeba (Naegleria, Acauthmoeba)

Chronic Meningitis Deﬁned as symptoms + CSF pleocytosis for 4 wks

Mycobacterium tuberculosis (Adult) Intensive 2 months treatment : Medium dose steroid cover for Isoniazid 5 -10mg/kg/day po MRC 2 and 3 patients : + Rifampicin 10 mg/kg/day po Dexamethasone : 12 – 16 mg /day x + 2 – 3 weeks, then taper over 2 – 3 Pyrazinamide 25 mg/kg.day po weeks (4 – 6 weeks total) + Streptomycin 0.5-0.75 g/kg/day IM 9 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

In patients at low risk for therapeutic failure Induction : combination of AmBd plus flucytosine for only 2 weeks, (ie, they have an early diagnosis by history, Consolidation : fluconazole 800 mg od for 8 weeks Maintenance : fluconazole 200 mg od for 6–12 months no uncontrolled underlying disease or Immunocompromised hosts: immunocompromised state, See Infections in HIV patients ( chapter 3)

Neurosyphilis

Benzylpenicillin (Pen G) 3-4 Ceftriaxone 2g q24h IV x 2 In HIV/AIDS, give higher doses & MU wks longer periods of therapy. q4h IV x 2 wks OR Procaine penicillin 2.4 MU q24h IM + Probenecid 500mg qid po x 2 wk 11 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment according to DIFFERENT SITE EENT Infections (Eye, Ear, Nose, Throat) Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Conjunctivitis Non-gonococcal G. Chloramphenicol Take conjunctival swab S. aureus 1-2 drops q4h (monitor S. pneumoniae for improvement) H. inﬂuenzae S. pyogenes Gonococcal ophthalmia neonatorum IV Cefuroxime 15mg/kg IV Ceftazidime Or IV Frequent saline irrigation of q12h x 10days Cefotaxime discharge. Refer to ophthalmologist. + + Gutt. Chloramphenicol 1-2 Gutt. Ceftazidime 1-2 drops N. gonorrhaea drops every 60 mins then every q6h q6h as infection improves

Chlamydia Erythromycin 25mg/kg BD PO for 14 days Refer to Ophthalmologist ophthalmia neonatorum + Gutt. Chloramphenicol eye drops 1-2 drops every 30 Chlamydia trachomatis mins then q6h as infection improves Keratitis Herpes simplex Topical Occ. Acyclovir 5x/day Refer all cases to Ophthalmologist H. simplex, types 1 &2 12 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Varicella-zoster ophthalmicus Topical Occ. Acyclovir 5x/day Refer all cases to Ophthalmologist T. Acyclovir 800mg PO 5X/ day for 1 week

Bacterial (contact lens user) Gutt. Gentamicin 1.4% Gutt. Moxifloxacin Refer all cases to Ophthalmologist. P. aeruginosa (14mg/ml) :loading dose (Vigamox) 1-2 hourly Cornea scrapping for C&S MUST be then 2 hourly for 2-5 days taken prior to starting Abx and taper + Gutt. Ceftazidime (Fortum) 5% (50mg/ml): loading dose then hourly for 2-5 days then taper * (loading dose: 1-2 drops every 15 mins for the first 2 hrs.) Subconj. dose: Gentamicin 20mg in 0.5 mls Ceftazidime 100mg in 0.5 mls Simple Bacterial Gutt. Ciprofloxacin (Ciloxan) Gutt. Chloramphenicol 1-2 Refer all cases to Ophthalmologist. 1-2 drops q2-4h drops q2-4h Cornea scrapping for C&S MUST be Gram positive organisms taken prior to starting antibiotic 13 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Fungal Keratitis Gutt. Amphotericin B 0.3% Gutt. Fluconazole 0.2% Refer all cases to Ophthalmologist. Yeast (3mg/ml) +/- T. Fluconazole (2mg/ml) and T. Ketocon- Cornea scrapping for 200-400mg/ day azole 400-600mg/day KOH and C&S MUST be taken prior to starting antifungal

Filamentous Gutt. Natamycin 5% hourly Gutt. Amphotericin B 0.3% Refer all cases to Ophthalmologist. +/- T. (3mg/ml) Cornea scrapping for KOH and C&S Fluconazole 200-400mg/ day or MUST be taken prior to starting Gutt. Fluconazole 0.2% antifungal (2mg/ml) and Ketoconazole 400-600mg/day

Endophthalmitis Bacterial Endophthalmitis Ceftazidime: Common combination for - Intravitreal 2.25mg/0.1ml intravitreal antibiotics: Gram-positive - Subconjunctival 100mg Vancomycin and Ceftazidime. May Staphylococcus epidermidis, - Topical 50mg/ml (5%) repeat after 48-72 hours Staph. aureus, Streptococcus pneumonia, Vancomycin: May add intravitreal amphotericin Strep. spp., etc. - Intravitreal 1mg/0.1ml B if fungal infection is suspected - Subconjunctival 25mg Topical 50mg/ml (5%) 14 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Gram-negative Amikacin: Risk of retinal toxicity with Pseudomonas aeruginosa, - Intravitreal 400ug/0.1ml intravitreal administration - Subconjunctival 40mg Normal renal function Bacteroids sp, - Topical 20mg/ml Recommended for culture-negative Enterococcus sp, endophthalmitis Gentamicin: - Subconjunctival 20mg Others, - Topical 10-20mg/ml Propionibacterium acnes, Ciproﬂoxacin: Corynebacterium species. - Topical 0.3% solution - Intravenous 200-400mg q12h - Oral 750mg q12h (x 14 days) Moxiﬂoxacin: - Topical 0.5% solution - Oral 400mg od (x 10 days) Clarithromycin: - Oral 500mg q12h (x 14 days) 15 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Fungal Endophthalmitis Amphotericin B: Common/initial antifungals: Candida species, - Intravitreal 5-10ug/0.1ml Intravitreal , topical and systemic - Subconjunctival 0.8–1mg amphotericin B Aspergillus sp. - Topical 0.15-0.5% +/- Fusarium species, etc. - Intravenous 0.8-1mg/kg/day Topical/oral Fluconazole Fluconazole: May repeat intravitreal - Subconjunctival 2%/1.0ml injection after 48-72 hours or may - Topical 0.2% solution consider to give intravitreal - Intravenous/oral 200-400mg od voriconazole in unresponsive case Voriconazole: - Intravitreal 100ug/0.1ml - Topical 1-2% solution - Oral 200mg q12h Miconazole: - Intravitreal 10ug/0.1ml - Subconjunctival 5mg - Topical 10mg/ml 16 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Orbital cellulitis

Strep pyogenes, Amoxicillin/Clavunalate 1.2g q8h IV 1. Depends on culture & sensitivity Strep pneumonia, or results Staph aureus, Ceftazidime 50mg/kg 6h IV Haemophilus inﬂuenza (children) or 2.Children dosage to adjust Metronidazole 500mg 8h IV according to body weight 3.Surgical drainage is needed in severe cases with periosteal/orbital abcess

Preseptal cellulitis Mild : Amoxicillin 500mg/ 1.Antibiotic regime should cater Cloxacillin 500mg q6h po Clavunalate 125mg to results of culture & sensitivity Strep pyogenes, Severe: Strep pneumonia, Amoxicillin/Clavunalate 1.2g bd po 2.Children dosage to adjust Staph aureus, q8h IV according to body weight and/or Haemophilus inﬂuenza (children) Ceftazidime 50mg/kg 6h IV and/or Metronidazole 500mg 8h IV 17 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Ear Treatment should include gentle Otitis Externa (Swimmer’s ear) Sofradex Ear Drop q8h x 1wk Oﬂoxacin Ear Drop q12h x 1wk cleaning. (Tympanic membrane intact) Add oral Cloxacillin Pseudomonas sp., 500mg q6h if there is furunculosis. Enterobacteriaceae, Proteus sp. Fungal element must be removed for ear drops to be eﬀective. Candida albican Clotrimazole Ear Drop q6-8h x 2 wk (*Nystatin ear Drop q6-8h x 2 wk) ENT referral is advised. Aspergillus niger Not available anymore

Necrotizing otitis externa Ciproﬂoxacin 400 mg q12h IV x 2wks Cefoperazone/sulb 1 g q12h IV Referral to ENT is mandatory Pseudomonas sp. followed by 500 mg q12h po followed Surgical debridement required x 3-4 wks by Ciproﬂoxacin 500 mg q12h po when not responding to antibiotic x 3-4 wk or involving the cranial nerves. 18 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Acute Otitis media OR Mastoiditis Amox/Clav 1.2 g q8h IV x 10 days Cefuroxime 250-500 mg q12h po x When ear drum is perforated, add Pneumococci (20-25%), 10days ear drops. If persistent, prolonged H. inﬂuenzae (15-30%), or recurrent refer to ENT. If M. catarrhalis(3-20%), mastoiditis not responding to Group A Strep (20%), antibiotic, surgical debridement S. aureus (1%) is advised Viral (35%)

Chronic otitis media Sofradex Ear Drops q8h x 2 - wk Oﬂoxacin Ear Drop q12h x 2 – 3 wk Ear toilet must be performed S. pneumoniae (22%), before instillation of ear drops. S. pyogenes (16%), If severe requiring hospitalization, S. aureus (7%), use Ceftriaxone 1 g q12h IV H. inﬂuenzae (4%), P. aeruginosa 19 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Febrile neutropenia patients –Empirical and preemptive therapy (For detailed information please refer to PTS Hematology / Chemotherapy Book ) Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Aerobic Gram positive & negative pathogens *Pip/Tazo 4.5 g q6h IV or Ertapenem (if not at risk Third line: including CONS, S. aureus, P. aeruginosa, * Cefepime 2 g q8h IV for pseudomonas),: Meropenem, Anti- fungal aspergillus, candida + Imipenem Subsequent Rx: * Doripenem: Amikacin 15-20 mg (if nosocomial pneumonia) q24h IV ± If suspect resistant #Vancomycin 1 g q12h IV( multidrug resistant bacteria, or Dose adjusted according to may need to initiate Polymyxin, Netilmicin 4 – 6 mg/kg Target Trough Level) Or q24h IV or Tigecycline Teicoplanin 6 mg/kg q12h Or for 3 doses, then 6 mg/kg Bactrim q24h IV) Assessment of risk for complications of severe infection should be undertaken at presentation (A-II). Initial therapy include β-lactam agents plus aminoglycoside (A-I). Low risk patients: (anticipate neutropenia ≤ 7 days or no co-morbidities or pts with MASCC score > 21) may be conisered for monotherapy [A-I}. In combination Rx, use aminoglycoside for 5-7 days if no gram negative bacteremia & pt is stable #Vancomycin (or agents active against aerobic gram+ cocci) is not recommended as a standard part of the initial empiric Rx (A-I). Indications for addition of for speciﬁc clinical indications (suspect catheter- related infection, skin/soft tissue infection, pneumonia, hypotension, severe mucositis, colonization with MRSA) Metronidazole may be added in the presence of severe mucositis, intraabdominal infection, perrectal abscesses or pseudomembranous colitis 20 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Modify initial empiric Rx for pts at risk for infection with resistant bacteria (previous infection or colonization with the organism and recent outbreaks e.g. MRSA, ESBL-orga) Deescalate Rx according to susceptibility testing.

Empiric anti-fungal if persistent fever after 4-7 Fungi (yeast: candida, mold: aspergillus), Low-risk of invasive mold Anidulofungin 200mg, then days of a broad-spectrum antibiotic + no infection: 100mg/d identified fever source (A-II) #Lipid formula- Fluconazole 400 mg IV/PO, tions are more expensive but have less renal then 200mg toxicity and infusion side-effects. They have [A-I] different efficacies and dose recommenda- Loading 400 – 800 mg tions. Other echinocandins have not been (Sanford- 800mg loading studied specifically in empiric therapy but may then 400mg maintenance be alternatives. Capsule itraconazole has dose) unreliable absorption and is not High-risk of invasive mold Conventional Amphotericin recommended as empirical therapy infection (empirical) B 0.5-0.7mg/kg/day(B-I) Voriconazole as primary choice for preemp- #Lipid-Amphotericin B IV tive and directed therapy for invasive 3mg/kg/day [A-I] or aspergillosis. Amphotericin B as primary or choice for mucomycosis. Preemptive therapy Caspofungin IV 70mg D1 Itraconazole 200mg bd iv or directed therapy involves close monitoring and 50mg daily [A-I] or for 2 days then 200mg iv of neutropaenic patients with sinus CT or Voriconazole 6mg/kg/day daily for 7 days followed by chest/ abdominal CT and serial galactoman- bd iv for 2 days then oral solution 200mg bd (A-I) nan tests Lipid formulation (if intolerant to 3mg/kg/day bd iv conventional Amphotericin B , proven Invasive or Fungal Infection or mucomycosis) or orally 200mg bd (B1) Caspofungin 21 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment according to DIFFERENT SITE GASTROINTESTINAL INFECTION Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Biliary System Gallbladder Cefoperazone 1 g q12h IV x Amox/Clav 1.2 g q8h IV In acute cholecystitis, switch to 5 - 7d Cefuroxime 250 mg q12h po or Cholecystitis,cholangitis, biliary sepsis (stones) + Amox/Clav 625 mg q12h po Metronidazole 400 mg depending on clinical recovery Enterobacteriaceae (68%), q8h IV x 5 – 7d Enterococci (14%), Patients with acute cholangitis with Bacteroides (10%), stent, cover for multiply resistant hosp strains of Gm -ve bacilli Clostridium sp. (7%) including P. aeruginosa consider Pip/Tazo Gastroenteritis EMPIRICAL THERAPY Ab not indicated Usually self-limiting. ORT mainstay of therapy. Mild to moderate Anti-motility agents contraindi- Viral, parasite & bacterial cated in children. Severe Ciprofloxacin 400 mg q12h TMP/SMX 2 tab q12h po x Most travelers’ diarrhea falls into (> 6 unformed stools and/or temp.,bloody stool) IV 3-5d this category. OR Shigella, salmonella, C. jejuni, E. coli 0157: H7, 250 mg - 500 mg q12h po x toxin +ve C. difficile, E. histolytica 3-5d SPECIFIC THERAPY Azithromycin 500 mg q24h Ciprofloxacin 500 mg q12h po x 3d OR EES 800 mg Campylobacter jejuni po x 3-5d q12h po x 7d 22 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Clostridium diﬃcile toxin - positive antibiotic Metronidazole 400 mg q8h Vancomycin 125 mg q6h po Avoid antimotility agents. Use associated colitis po x 7d x 7d Vancomycin 125mg q6h po x 10d if not responding. E. coli 0157: H7 No antimicrobial therapy recommended CID 1996; 22: 813. Therapy may increase risk of haemolytic ureamic syndrome. Cryptosporidium parvum, * Nitazoxanide 500 mg po q12h x 3d Symptomatic treatment. Metronidazole NOT eﬀective * Not registered in Malaysia Entamoeba histolytica Metronidazole 800 mg Tinidazole 1 g q12h po x 3d Liver abscess: look under LIVER. q8h po x 10d Gardia lamblia Metronidazole 250 mg Tinidazole 2 g stat Liver abscess: look under LIVER. q8h po x 5d

Isospora belli TMP/SMX x 1 tab q12h po x 10d. If AIDS pt 1 tab q6h x 10 d then q12h x 3 wks Listeria monocytogenes Ampicillin 50 mg/kg q6h IV TMP/SMX 20 mg/kg/day IV divided by q6-8h Microsporidia Albendazole 400 mg q12h po, then chronic suppression Salmonella Supportive ONLY Antibiotic may prolong carrion state. (non-typhi/non paratyphi) 23 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Shigella TMP/SMX 2 tabs q12h po x Ciprofloxacin 500 mg q12h Antibiotic may prolong carriage 3d po x 3d state. Vibrio cholerae Doxycycline 300 mg po stat Ciprofloxacin 500 mg q12h Use Ciprofloxacin if there is Primary therapy is po stat doxycycline resistance. hydration Duodenal (Gastric Ulcer) Helicobacter pylori Initial Therapy ( 7 days) OBTM (14 days) In areas where Clarithromycin resistance ( For algorithm pls see next page) Amoxicillin 1 g q12h po Omeprazole (20 mg bid) rate ↑: PPI + Amoxicillin + Metronidazole + Bismuth subsalicylate 400mg q12h po Cure rate 86 – 90% after Omeprazole 20 mg q12h po (120mg tds) Tetracycline therapy for 10 days. OR HCl (500 mg tds) Metron- Esomeprazole 20 mg q12h idazole (500 mg tds) There are currently insufficient data to po recommend *sequential therapy as OR Meta-analyses show that a alternative first-line for H. pylori therapy in 14-day course of therapy is Asia. ( 2nd Asian Pacific Meeting on H. Pantoprazole 40 mg q12h slightly superior to a 7-day Pylori 2012) po course. + Proton pump inhibitor to be taken half an Clarithromycin 500 mg hour before food q12h po Smoking adversely affects outcome of HP *Sequential therapy eradication therapy. PPI + Amoxycillin = 5 days Followed by PPI + If failed, to follow the algorithm below. Clarithromycin + Bismuth is not available in our center. Metronidazole= 5 days (total 10 days of treatment) 24 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

ALGORITHM 1: HELICOBACTER PYLORI INFECTION

PPI triple therapy/Sequential therapy

Failure

Quadruple therapy PPI twice daily Metronidazole 500mg tds Tetracychne 500mg tds Bismuth 120mg tds

Failure

Empiric salvage therapy: Susceptibility testing with PPI BD + tailored therapy Amoxycilline 1g bd + Either Levoﬂaxacin 500 mg bd for 10 days or Rifabutin 300 mg bd for 10 days Or Furazolidone 200-400mg/day/for 10 days 25 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Diverticulitis No signs of bowel perforation Cefoperazone 1 g q12h IV Ertapenem 1 g q24h Treat until afebrile 3-5d Enterobacteriaceae, + IV Bacteroides Metronidazole 400 mg q8h Enterococci po x 7d Hepatic Abscess : Pyogenic Abscess Ceftriaxone 2 g q24h IV Ertapenem 1 g q24h IV If serology for amebiasis negative, Enterobacteriaceae,bacteroides, + consider drainage of abscess. enterococci Metronidazole 500 mg q8h Change to oral Metronidazole 800 IV mg q8h when pt improves. Treat for Metronidazole 500 mg q8h Amoebic abscess IV 10 days. Conﬁrm sensitivities with culture. Hepatitis Viral hepatitis Hepatitis B immune Give within 12hrs of exposure or Hepatitis B globulin (100iu/0.5ml or within 48hr post-delivery for Post-exposure prophylaxis ( see Chapter 3b: Viral) 100200iu/ml). Perinatal: neonate prophylaxis. For sexual 0.5ml IM. Percutaneous: exposure, give within 14 days of 1ml IM. Sexual: 1ml IM sexual contact 26 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Chronic hepatitis B Pegylated Interferon Adefovir 10 mg Indication :- 2a/2b/weekly SC x 48 wks q24h po Persistent high ALT > 2 ULN HBV Or DNA ≥ 20,000 iu/ml (For HBeAg Neg) Entecavir 0.5 mg q24h Immediate treatment maybe po Or required if jaundice or Telbivudine 600mg q24h po decompensated Or Tenofovir 300mg q24h po

Chronic Hepatitis C Ribavirin 400 mg am 600 mg pm po + Pegylated For ESRD ( CrCL <10ml/min), Genotypes 1&4 Interferon alfa 2a/2b/weekly SC x 48 Ribavirin is contraindicated, use wks Pegylated Interferon alfa 2a: 135mcg/week SC or alfa 2b weight-based Genotypes 2-3 Ribavirin 400mg am 600mg pm po + Pegylated Interferon alfa 2a/2b weekly SC x 24 wks Pancreas Pancreatic Abscess, Imi/Cilas 500 mg q6h IV Pip/Tazo 4.5 g q8h IV Antibiotics NOT required in initial Infected Pseudocyst, Infected Necrosis therapy of acute pancreatitis. Enterobacteriaceae, enterococci, S. aureus, S. epidermidis, anaerobes, candida 27 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Perirectal abscess

Enterobacteriaceae, Bacteroides Cefoperazone 1 g q12h IV Amox/Clav 1.2 g Surgical drainage is most important (Enterococci) + q8h IV Metronidazole 400 mg q8h OR po x 7d Amox/Clav 625mg q12h po Peritonitis Primary (spontaneus) Cefoperazone 1g q12h IV Ertapenem 1 g q24h IV 30-40% are culture neg. if blood Enterobacteriaceae (63%), x x culture +ve, suggest treat 2 wks. S. pneumo (15%), 5-10d 5-10d Or Ceftriaxone 1g IV Switch to Cefuroxime 250 mg Enterococci (6-10%), q24h q12h po for discharge. Anaerobes (<1%) Splenectomy S. pneumoniae, Haemophilus influenzae, Ceftriaxone 2 g q24h IV Moxifloxacin 400mg Patient should have Pneumococcal, N. meningitidis q24 IV Meningococcal and H. Influenzae vaccination & receive prophylaxis with Penicillin V ( Please see Chapter 5c Medical Prophylaxis) For patient with bleeding disorders and there is concern about giving vaccinations, vaccinations. Can be given subcutaneously including HiB vaccine. 28 29 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Recommended Treatment according to DIFFERENT SITE GENITOURINARY TRACT & GYNAECOLOGICAL INFECTIONS (By anatomic site) Kidney/ Bladder/Urethra/Prostate/Epididymis/Testes/vagina

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Uncomplicated Cystitis E coli TMP/SMX 160/800mg Cefuroxime 250mg Avoid tetracyclines or Klebsiella q12h PO q12h PO x 3d ﬂuoroquinolones in children Proteus x Avoid Bactrim (TMP/SMX) Staphylococci 3d or Nitrofurantoin 100mg in pregnancy q12h PO x 5d Uncomplicated Pyelonephritis E coli Ciproﬂoxacin 500mg Amox/Clav 625mg Consider parenteral treatment if Proteus q12h PO q12h PO x 14d severe before switching to oral Klebsiella x regimen Other enterobacteria 7-10d Staphylococci 29 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Complicated UTI (with or without pyelonephritis)

E coli Ciproﬂoxacin 400mg q12h IV Amox/Clav 1.2g q12h IV Continue 3-5 days after fever settles Proteus or control/elimination of Klebsiella complicating factors Enterococci Pseudomonas Staphylococci Enterobacter

Gonococcal Urethritis

N gonorrhea (50% has concomitant C Ceftriaxone 250mg IM stat Cefotaxime 500mg IM stat Dilute Ceftriaxone in Lignocaine trachomatis) or Azithromycin 1g PO stat or Doxycycline 100mg q12h PO x 7d Non Gonococcal Urethritis C trachomatis Azithromycin 1g PO x 1d or Erythromycin 500mg q6h M genitalium Doxycycline 100mg q12h PO x 7d or EES 800mg q6h PO x 7d PO x 7d 30 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Acute / Chronic Prostatitis

E coli Ciproﬂoxacin 500mg TMP/SMX 160/800mg Acute Other enterobacteria q12h PO q12h PO - Consider starting IV if severe before switching to oral Pseudomonas - Total duration of Enterococci 4 weeks Staphylococci Chronic -Total duration of 4-6 weeks or longer

Ureaplasma Ceftriaxone 1g IV stat + Erythromycin 500mg q6h PO Doxycycline 100mg q12h x 7d or EES 800mg q6h PO x 7d PO x 7d

Epididymitis/Epididymoorchitis Suspected STD due to Gonococcal Ceftriaxone 250mg IM stat + Doxycycline 100mg 12h Dilute Ceftriaxone in Lignocaine or Chlamydial infection PO x 10d

Related to UTI (Enteric organism) Ciproﬂoxacin 500mg q12h TMP/SMX 160/800mg q12h PO x 14d PO x 10d or Amox/Clav 625mg q12h PO x 10d 31 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Pelvic Inﬂammatory Disease

Mild to moderate PID (no tubo-ovarian abscess): IM ceftriaxone 250mg stat, IM ceftriaxone 250mg stat Outpatient management followed by doxycycline followed PO 100mg BD by Azithromycin PO + 1g/week Chlamydia trachomatis Metronidazole po for 2 weeks Neisseria gonorrhea 400mg Mycoplasma genitalium BD (14 days) Anaerobes Severe PID/tubo-ovarian abscess/intolerance or IV ceftriaxone 2g daily 1)IV clindamycin 900mg Though PID in pregnancy is rare, not responding to oral therapy: + Doxycycline OD plus if found to be pregnant, tetracycline PO 100mg BD + 2)IV gentamicin (2mg/kg should be avoided. A combination (Intravenous antibiotic should be continued metronidazole 400mg loading followed of cefotaxime, azithromycin and until 24 hours after clinical improvement) BD PO (14 days) by 1.5mg/kg TDS), metronidazole for 14 days followed by clindamycin can be used. 450 mg QID PO ( 14 days) OR 1) Doxycycline po 100mg BD plus 2)metronidazole 400mg BD po (14 days) 32 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Vaginitis anaerobic or microaerophiles organisms Metronidazole po 500 mg Neo-Penotran 1 suppository If allergic to Metronidazole, (Gardnerella vaginalis, bd for 7 day, or bd for 14 days, Clindamycin 300 mg twice daily Prevotella species, Mycoplasma hominis, • Metronidazole or Neo-Penotran Forte 1 po for 7 days suppository OD for 14 days. Mobiluncus species) 2 g single dose po • Neo-Penotran 1 suppository at night for 14 days, or 1 suppository bd for 7 days

VAGINAL CANDIDIASIS Nystatin pessary 100,000 Miconazole pessary units 100mg daily Candida species, commonest – candida albican for 14 days for 7 days • Fluconazole 150 mg stat OR Clotrimazole pessary • Itraconazole 200mg 100mg BD for 1 day daily for 7 days or or 3 days 200mg for 3 days 33 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative UTI in Pregnancy

UNCOMPLICATED UTI Cefuroxime 250 mg Amox/Clav 625 mg Cystitis in pregnancy, (cystitis, urethritis) q12h po x 7-10d q12h po x 7-10d do not use tetracycline Escherichia coli (E. coli) and quinolones. Nitrofurantoin, Proteus mirabilis TMP/SMX avoid at third trimester Klebsiella pneumoniae enterococci including Gardnerella vaginalis and Ureaplasma ureolyticum Gram-positive organisms -Group B streptococcus,Staphylococcus saprophyticus and Staphylococcus haemolyticus

ACUTE Cefuroxime 1.5 g stat PYELONEPHRITIS then 750 mg q8h IV (in pregnancy)

(Society of Obstetricians and Gynaecologists Canada clinical practice guidelines. J Obstet Gynaecol Can 2008;30(8):702–708) , CDC Vaginal discharge - STD Treatment Guideline 2006 34 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Chorioamnionitis/Septic Miscarriage/Endomyometritis

Bacteroides IV Ampicillin 2 g stat and IV Ampicillin 2 g stat and In penicillin-allergic patients, IV Gp B & A Streptococcal every 6 hours every 6 hours Vancomycin 1 g every 12 hours to Escherichia coli plus plus substitute the IV Ampicillin. Mycoplasma hominis IV Gentamicin 1.5 mg/kg IV Gentamicin 1.5 mg/kg ACOG educational bulletin. Antimicrobial Gram-negative anaerobes every 8 hours every 8 hours plus IV therapy for obstetric patients. Number Ureaplasma urealyticum plus Clindamycin 900 mg 245, March 1998. Int J Gynaecol Obstet. Gardnerella vaginalis Metronidazole 500 mg IV every 8 hours 1998; 61:299-308 Trichomonas vaginalis every 8 hours 35 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS INTRAVASCULAR CATHETER-RELATED INFECTION Short lines (SL) include Short-term Central Venous Catheter or arterial catheter-related Blood Stream Infection; Long lines (LL) include CVC & ports = LL Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Complicated – suppurative - - Remove catheter & treat with thrombophlebitis, systemic antibiotics for 4-6 weeks, , endocarditis, osteomyelitis etc 6-8 weeks for OM in adults

Uncomplicated bloodstream infection & fever Cloxacillin 2 g q4H First generation May retain CVC or P & use systemic resolves within 72 hours in a patient who has Vancomycin 15 mg/kg cephalosporin or antibiotics for 10-14 days & no evidence of suppurative thrombophlebitis & q12H vancomycin Daptomycin antibiotic lock therapy for 10-14 days. Remove if there is clinical endocarditis Coagulase-negative Staph aureus 6mg/kg/day or linezolid deterioration  systemic i) Methicillin susceptible ii) Methicillin resistant antibiotics min 7 days Staph aureus Cloxacillin 2 g q4H Vancomycin 15 mg/kg Remove catheter Systemic i) Methicillin susceptible Vancomycin 15 mg/kg q12H Daptomycin 6-8 antibiotics for ≥ 14 days for Short q12H mg/kg/day Linezolid Line; 4-6 weeks for Long Line ii) Methicillin resistant Vancomycin (plus rifampicin or gentamycin) Bactrim (TMP/SMX) alone if susceptible Enterococcus Ampicillin 2g q4H or q6H± gentamicin 1 mg/kg q8H For Short Line: Remove catheter & i) Amp susceptible Systemic antibiotics for 7 - 14 days 36 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

ii) Amp resistant, vancomycin susceptible Vancomycin 15mg/kg q12H ± Gentamicin 1 For Long Line: May retain Central mg/kg q8H Venous Catheter or Port & use systemic antibiotics for iii) Amp resistant, vancomycin resistant Linezolid 600mg q12H or 7-14 days & antibiotic lock therapy Daptomycin 6mg/kg/day for 7-14 days. Remove CVC or P if there is clinical deterioration For SL: Remove catheter Systemic E.coli & Klebsiella sp antibiotics for 7 - 14 days i) ESBL-ve 3rd gen cephalosporin eg Ciproﬂoxacin or Ceftriaxone 1-2 g/day Aztreonam For LL: Remove catheter& systemic ii) ESBL +ve antibiotics for 7 - 14 days. If need to salvage LL, systemic & antibiotic lock therapy for 10-14 days. Ertapenem 1 g/day Ciproﬂoxacin or Imipenem 500mg g6H If no response, remove Aztreonam CVC/P & rule out endocarditis Meropenem 1g q8H or suppurative thrombophlebitis, & if not present, treat with antibiotics for 10-14 days

Acinetobacter sp Amp/Sulb 3g q6H or, Polymyxin B, Tigecycline Imipenem 500mg g6H Meropenem 1g q8H 37 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Stenotrophomonas maltophilia TMP-SMX 3-5 mg/kg Ticarcillin (trimethoprim & component) q8H Clavulanic acid

Cefepime 2g q8H Pseudomonas aeruginosa or Sulperazone, Imipenem 500mg g6H Doripenem or Meropenem 1g q8H or Pip/Tazo 4.5g q6H, Amikacin 15mg/kg q24H

Burkholderia cepacia TMP-SMX 3-5 mg/kg (trimethoprim component) q8H or Imipenem 500mg g6H or Meropenem 1g q8H 38 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Candida albicans or other Candida sp Caspofungin 70mg loading Lipid Amp B Remove catheter dose then 50 mg/day Antifungal therapy for 14 days or after the ﬁrst negative blood culture Anidulafungin 200mg loading dose then 100 mg daily or ﬂuconazole 400- 600mg/day

Notes: 1. When denoting the duration of antimicrobial therapy, day 1 is the ﬁrst day on which negative blood culture results are obtained (C-III). 2. Linezolid should not be used for empirical therapy (i.e.,in patients suspected but not proven to have CRBSI) (A-I).Catheter Related Blood stream infection 3. Empirical combination antibiotic coverage for MDR gram-negative bacilli, such as P. aeruginosa, should be used when CRBSI is suspected among neutropenic patients, severely ill patients with sepsis, or patients known to be colonized with such pathogens 4. Empirical therapy for suspected catheter-related candidemia should be used for septic patients with any of the following risk factors: total parenteral nutrition, prolonged use of broad-spectrum antibiotics, hematologic malignancy, receipt of bone marrow or solid-organ transplant, femoral catheterization, or colonization due to Candida species at multiple sites (B-II). 5. Antibiotic lock therapy should be used for catheter salvage (B-II); however, if antibiotic lock therapy cannot be used in this situation, systemic antibiotics should be administered through the colonized catheter (C-III).

Source: Mermel LA et al. CPG for the Diagnosis and Management of IV Catheter-Related Infection: 2009 Update by the IDSA. Clinical Infectious Diseases 2009; 49:1-45 39 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment According to DIFFERENT SITE ODONTOGENIC Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative ODONTOGENIC INFECTION Oral microﬂora: Amox/Clav 625mg Amox/Clav 1.2 g q8h IV Oral surgery consultation highly spirochaetal org., streptococci, anaerobes q12h po x 5d x 5d advised to rule out odontogenic in + + origin Metronidazole 400 mg Metronidazole 500 mg _Mainstay of treatment in abscess cases are drainage and aggressive q8h po x 5d (mild q8h IV x 5d (severe, therapeutic infection) spreading infection)

Streptococcus species (95%), Mild to moderate Amox/Clav PO Amox/Clav for pts who have Peptostreptococcus, infection 625mg q8h x 5-7 days previously been treated with a Peptococcus, Pen V PO 500 mg q6h po OR β-lactam antibiotic & still have an Actinomyces, ± Cephalexin PO500 mg q6h unresolved infection or infected Lactobacillus (gram + anaerobes) OR with β-lactamase-producing Metronidazole PO 400 mg organisms include Bacteroides, • Bacteroides, *erythromycin q8h x 5-7 days Prevotella sp. Veillonella, and Fusobacterium. OR (anaerobic gram-neg) * Clindamycin *For Penicillin allergy patients 40 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment According to DIFFERENT SITE ODONTOGENIC Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Severe infection Clindamycin is a good alternative to Clindamycin penicillin in mild to moderate OI PO 150-300 mg q6h-8h where β-lactamase producing organisms may be present, and its x 5-7 days broad spectrum makes it the drug of choice for empiric therapy of severe OI. Appropriate dental procedures should always be the ﬁrst line of care, with antibiotics serving as adjunctive therapy Antibiotic therapy is indicated primarily when drainage cannot be adequately established, when the infection has spread 41 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment According to DIFFERENT SITE ODONTOGENIC Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative ODONTOGENIC INFECTION to the surrounding soft tissue, or when systemic symptoms are evident. Early and aggressive treatment with both surgery and antibiotics is indicated in immunocompromised patients in order to prevent progression of disease. Source: CPJ/RPC • DECEMBER 2004/JANUARY 2005,

VOL. 137, NO. 10: 25-29 42 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment according to DIFFERENT SITE Respiratory Tract Infection Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative UPPER RESPIRATORY TRACT Amox/Clav 625 mg Cefuroxime 500 mg If severe, it may be necessary to Acute pharyngitis/ start with parenteral antibiotic. If Laryngitis/Tonsilitis q12h po x 1 wk q12h po x 1 wk recurrent, surgery is mandatory. Strep. pyogenes virus (laryngitis) Diphtheria Benzylpenicillin (Pen G) 1 MU /kg/day in divided Antitoxin is critical in management Corynebacterium diphtheriae q6h IV x 7d 1 Mega unit Pen G = 0.6g

Acute epiglottitis Cefuroxime 1.5 g stat then 750mg q8h IV x 10d H. infuenzae S. pneumoniae Acute otitis media/sinusitis Amox/Clav 675mg q12h po x 10d Strep. pneumoniae, H. influenzae, Moraxella Cefuroxime 500 mg q12h po x 10d catarrhalis, Clamydia Acute tracheobronchitis Erythromycin ES 800 mg q12h po x 5d Most are of viral origin Viral, M. pneumoniae, C. pneumoniae, B. pertussis 43 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS Recommended Treatment according to DIFFERENT SITE Respiratory Tract Infection Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative UPPER RESPIRATORY TRACT Acute bacterial exacerbation of chronic Azithromycin 250 – Erythromycin ES 800 Value of antibiotic in mild bronchitis 500 mg q24h po x 3d mg q12h po x 5d exacerbations controversial Viral, + OR S. pneumoniae, Amox/Clav 625 mg Azithromycin 250-500 H. influenzae, Moraxella catarrhalis q12h po mg q24h po x 3d OR OR Cefuroxime 250 – 500 Moxifloxacin 400 mg mg q12h po q24h po/iv x 5d

LOWER RESPIRATORY TRACT (Pneumonia) Community – acquired Erythromycin ES 800 Clarithromycin 500 mg Treat M. pneumoniae for Adults mg q12h po x 5d q12h po x 5d 14-21 days with macrolide (out-patient Rx, no co-mobidity) OR or ﬂuoroquinolone. S. pneumoniae, Azithromycin 500 mg K. pneumoniae, q24h po x 3d M. pneumoniae OR C. pneumoniae Amoxycillin 500mg tds Resp. viruses, H. inﬂuenzae Legionella sp. C. psittaci For all patients, consider tuberculosis. 44 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Adults Amox/Clav 625 mg q12h Moxifloxacin 400 mg q24h po x 5d OR (out-patient Rx, with co-morbidity) Cefuroxime 500 mg q12h po + Erythromycin ES 800 mg q12h po OR Azithromycin 500 mg q24h po x 3d Adults (hospitalized) Amox/Clav 1.2 g q8h IV + Ceftriaxone 1-2 g q24h IV Consider different antibiotic class if + patient had received previous As above plus anaerobes (if aspiration risk is Azithromycin 500 mg q24h antibiotic treatment in the IV/ po x 5d Azithromycin 500 mg q24h high), Moraxella, coliforms, resp. viruses, IV x 3-5d OR preceding 3 months. Coxiella burnetti Moxifloxacin 400 mg q24h In suspected melioidosis, use IV (MONOTherapy) Ceftazidime 2 g q8h IV Switch antibiotic according to sensitivity. TMP-SMX Double Switch to po when the pt's Community-acquired MRSA (CA-MRSA) Strength /Clindamycin condition has improved. For severe Influenza A (seasonal) /doxycycline cases, use alternative regimes. If risk factors* for pseudomonas Oseltamivir 75mg aeruginosa use anti-pseudomonal bid po for 5 days beta-lactam (pip-tazo, cefepime, ceftazidime) * Use of broad- spectrum antibiotic in past month, bronchiectasis, malnutrition , steroid use. May occur with or post -influenza 45 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Aspiration pneumonia + lung abscess, Amox/Clav 1.2 g q8h IV Clindamycin 450-900 mg Clindamycin 600 mg q6h po maybe empyema q8h IV OR used in lung abscess after initial IV Ceftriaxone 2 g q24h IV therapy. Prolonged Rx up to 4 + months may be necessary. Bacteroides (15% B. fragilis), peptostreptococci, Metronidazole 500 mg q8h Empyemas should be drained. Fusobacterium sp., S. milleri group, nocardia IV x 2wks (dual therapy) S. pneumoniae, Grp A Strep, S. aureus, OR Moxiﬂoxacin 400 mg q24h H.inﬂuenzae, K. pneumoniae IV/po

Anaerobic strep, Enterobactericeae

Hospital-acquired Pneumonia Early onset hospital-acquired pneumonia (2-4 Ceftriaxone 1- 2 g q24h Ertapenem 1 g q24H IV Organisms in early HAP mirror that days) and no risk for multidrug-resistant IV OR in the community; the regimes do or not cover Pseudomonas. organisms Moxifloxacin 400 mg S. pneumoniae, H.influenzae, Methicillin-sensitive Amox/Clav 1.2 g q8h IV S. aureus. Antibiotic-sensitive enteric or q24h iv Choices of oral therapy for Gram-negative bacilli: E. coli K. pneumoniae, Cefoperazone/Sulb 1-2 g de-escalation: Cefuroxime 500 mg Enterobacter sp, Proteus sp, Serratia marcescens. q12H IV q12H Moxifloxacin 400 mg q24H Amox/Clav 625 mg q12H 46 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Late onset hospital-acquired pneumonia (≥5 Pip/Tazo 4.5 g q8h IV Imipenem/Cilastatin Organisms in HCAP and late-onset HAP are days) OR 500 mg q6h IV more likely to be multidrug resistant Cefepime 1-2 g q12h IV OR organisms. Reserve polymyxin B in Acineto- Healthcare-associated pneumonia bacter infection proven to be multidrug- Aerobic Gram-negative bacilli Enterobacter, Meropenem 1 g q8h IV resistant. Consider combining Klebsiella, Acinetobacter, Pseudomonas sp., (Reserve carbapenems anti-pseudomonal agents and quinolone or Legionella sp., S. aureus, MRSA for ESBL-producing aminoglycoside in neutropenic sepsis and strains) confirmed Gram-negative bacteraemic patients who are unwell or not improving. Duration of aminoglycoside is 5-7 days. For MRSA, treat with vancomycin, alternative is linezolid. Add Erythromycin / Azithromycin if Legionello- sis suspected. In culture-negative patients, 7-10 days duration is as effective as 14 days. Culture-negative patients who have significant clinical improvement in 48-72H, consider antibitotic discontinuation.De-escalate to oral therapy in culture positive patients with significant response (except MRSA). In less severe HCAP patients, consider treating as outpatient using ciprofloxacin to cover Pseudomonas and adding azithromycin to cover atypical organisms. Suggested duration is 5 -7 days. 47 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Health Care Associated Pneumonia HCAP is used to designate patients with many co-morbidities who reside in nursing homes, other long-term care facilities, require home IV therapy or are dialysis pts. Normally resembles hospital-acquired pneumonia. Ventilator Associated Pneumonia (VAP) Lung infection in patient mechanically ventilated for more than 48 hours. Ventilator associated pneumonia (VAP) occurring less than 5 days of hospitalisation is less likely to be due to multidrug resistant (MDR) organism and has a better prognosis as compared to VAP occurring after 5 days of ventilation Less than 5 days hospitalised and without risk Ceftriaxone IV 1-2g q24h Amoxycillin/Clavulanate VAP bundle to reduce the incidence. of MDR IV 1.2g q8h 1. Daily interrupted sedation 2. Head up 30 degree positioning S.pneumonia 3. Peptic ulcer prophylaxis H.inﬂuenza 4. Deep vein thrombosis prophylaxis S.aureus 5. Daily assessment for extubation E.coli Monotherapy is favoured over K.pneumoniae combination therapy. Enterobacter spp. Duration of therapy 7-10 days Proteus spp. Serratia marcescens More than 5 days hospitalised and with risk of Piperacillin/tazobactam IV Imi/Cilas 500 mg IV q6h Monotherapy is favoured over MDR 4.5g q6h OR OR combination therapy Duration of P.aeruginosa Cefepime IV 2g q12h Meropenem IV 1 g q8h therapy 7 -10 days. Aminoglycoside may be added in selective case. Amikacin 15-20 mg/kg q24h IV 48 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

1 Acinetobacter spp. 1 Sulbactam/cefoperazone 2g q6h or Amoxycillin/ sulbactam 3g q6h for OR Netilmicin 4-6 mg/kg q24h IV No 2 Acinetobacter spp. (non clear evidence to suggest superior- K.pneumoniae (ESBL) multi resistant organism ity of combination therapy against (nMRO) monotherapy. Always consider the 2Use carbapenem for ESBL risk and beneﬁt. organisms. Consider ertapenem in clinically improving patient.

Acinetobacter MDR (multidrug resistant Polymyxin B 25,000 Duration of therapy 14 days. organism u/kg/day in two divided Polymyxin: 1mg base = 10,000units dose 100mg = 1 million units = 1 mega units Stenotrophomonas maltophilia TMP/SMX 15-20 mg/kg Doxycycline 100 mg q12h q24h IV (in divided doses) po

MRSA Vancomycin 15mg/kg bd Linezolid 600 mg q12h IV/ For serious infection, give (actual body weight) po vancomycin loading dose (Target trough level: 25-30mg/kg. 10-15μmol/L) 49 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Recommended Treatment According to DIFFERENT SITE SEXUALLY TRANSMITTED DISEASES (STDs) Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative GENITAL TRACT BOTH SEXES Doctor- administered: Patient-administered: Cryotherapy or electrocautery also Anogenital warts Trichloroacetic Acid ( TCA) Imiquimod 5% sachets eﬀective : Consult Dermatologist [Aldara®] ( non formulary) Consider HPV vaccination. Human papillomavirus 6, 11 3 times/wk GONORRHEA (urethritis, proctitis, prostatitis N. gonorrhoeae Ceftriaxone 1g IM/IV Oﬂoxacin 400 mg q24h Azithromycin 1 g stat may replace (50% has concomitant C. trachomatis) q24h x 1d po x 1d Doxycycline + + Doxycycline 100mg Doxycycline 100 mg q12h po x 14d q12h x 14 d Disseminated Gonococcal Infection N. gonorrhoeae Ceftriaxone 1 g q24h IV Cefotaxime 1 g q8h IV Treat for 7-10 days Non-gonococcal (urethritis/cervicitis) Doxycycline 100 mg q12h po Azithromycin 1g stat po Chlamydia (50%), Mycoplasma hominis (25%) OR Erythromycin ES 800 mg q12h po x 7 – 14d 50 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Herpes Simplex Herpes simplex Acyclovir 200 mg 5x/day Famciclovir 250 mg For chronic suppression (frequent virus - 2 po x 5days q8h x 5d recurrence) give either drug q12h po x 6 mths. Syphilis (Early primary, Secondary T. pallidum (< 2 year ) Benzathine Penicillin 2.4 Doxycycline 100 mg q12h Contact tracing of sex partners MU IM wkly x 2 wks po x 3 wks OR OR Procaine penicillin 1.2 MU Ceftriaxone 1 g q24h IM x q24h IM x 10day 4d

T. pallidum Late: Syphillis infection of Benzathine 2.4 MU IM weekly x 3 wk If allergic to Penicillin: more than > 2 year) Doxycycline 100 mg q12h po for 28 days

Congenital Pen G 50,000u/kg q12h IV x 10-14d Chancroid Ceftriaxone 250 mg IM x Azithromycin 1g po x 1d Haemophilus ducreyi 1day 51 Chapter 1A Recommended Treatment – Different Site : MEDICAL INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Lymphogranuloma venereum Chlamydia trachomatis Doxycycline 100 mg q12h Erythromycin ES 800 mg Doxycycline contraindicated in x 2 wk q12h po 2 wk pregnancy + breast feeding

Granuloma inguinale Calymmatobacterium granulomatis Doxycycline 100 mg q12h Erythromycin ES 800 mg 2 –3 wks q12h po 2-3 wk 52 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS Recommended Treatment according to DIFFERENT SITE BONE & JOINT INFECTIONS Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Osteomyelitis Haematogenous Cloxacillin 2 g q6h IV Vancomycin 1.0g q12h A microbiologic diagnosis is OR IV essential as it is difficult to predict Adult (>21 yrs) Cefazolin 2 g IV q8h (in proven MRSA the offending organism based on S. aureus most common + wide variety infection) epidemiology. Also take blood other aerobic/anaerobic cocci and bacilli culture and culture from affected site. Choice of antibiotic based on blood and bone culture report. Special circumstances Ciprofloxacin 400 mg Ceftriaxone 2 g q24h IV Sickle cell anaemia q12h IV Salmonella sp ACUTE Osteomyelitis with good vascular supply Post open reduction internal fixation Cloxacillin 2 g q6h IV Clindamycin 300 mg (ORIF), Open fractures Grade I & II fractures OR q6h IV/po Staphylococcus sp. Cloxacillin 500 mg q6h Gm-ve bacilli;Pseudomonas aeroginusa po MSSA 53 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

MRSA Vancomycin 1.0 g Teicoplanin 400 mg Choice of antibiotic is IVq12h + Ceftazidime q24h IV based on culture 2g q8h as primary until + sensitivity. culture report Rifampicin 450 mg available. q12h po + Fusidic acid 500 mg q8h po

Post-op prosthetic joint or post-op sternotomy Cloxacillin 2g q4h IV Vancomycin 1g bd No empiric therapy until culture + + and sensitivity results is available Staph. epidermidis (CONS) Rifampicin 450 mg Rifampicin 450 mg Surgical options ; refer to AAOS q12h po q12h po recommendation for the diagnosis Pseudomonas aeruginosa Ceftazidime 2.0g q8h of periprosthetic joint infections of + the hip and knee: Guideline and Ciproﬂoxacin 750mg evidence report . DO NOT initiate q12h po. antibiotic treatment in patients with suspected peri-prosthetic joint infection until after cultures from the joint have been obtained. 54 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Acute Osteomyelitis With Vascular Insuﬃciency

Pts with neurologi Cefuroxime 1.5g stat Amp/Sulb 1.5g q6h IV Surgical debridement is often c deﬁcit & decubitius; then 750 mg q8h IV OR mainstay of therapy. Duration of + Cloxacillin 2 g q6h IV treatment depends on respond.( atherosclerotic peripheral vascular dis; Metronidazole 500 mg + until ESR or CRP normalize) Need diabetic neuropathy q8h IV Gentamicin 4-6mg/kg bone culture and sensitivity. No q24h IV + empiric therapy unless acutely ill. Metronidazole 500mg Polymicrobic q8h IV organisms (aerobic & anaerobic pathologens)

CHRONIC Osteomyelitis (implies presence of dead bone)

S. aureus, Enterobacteriaceae, P. aeruginosa Empiric treatment not indicated. Choice of Debridement is necessary for antibiotic should be based on culture results. optimal respond to antibiotics. ( not beyond 6 weeks) 55 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Diabetic Foot Infection Acute, mild, no osteomyelitis Cefuroxime 750 mg Amox/Clav 1.2g q8h IV Gm +ve cocci q8h IV

Chronic, recurrent, limb threatening Cloxacillin 1g q6h IV Surgical debridement important Polymicrobic: aerobic cocci, bacilli and + aspect of management. anaerobes Gentamicin 4-6mg/kg q24h IV + Metronidazole 400 mg q8h po x 7-10d

Ulcer without inﬂammation Coloniser(skin ﬂora) – No antibacterial therapy

Ulcer with < 2cm of superﬁcial inﬂammation TMP-SMX-DS 1-2 tabs po bid + Cefuroxime Axetil Stap.aureus, S.agalactiae,S.pyogenes 500mg po q12h

Ulcer > 2cm of inﬂammation with extension Oral Amox/Clav + IV PIP-Tazo or Ertapenem to fascia TMP-SMX-Double 1 gm IV q12h Stap.aureus, Strength (980mg) IV S.agalactiae,S.pyogenes, coliforms – Ampi/Sulbactam 3gm IV q6h 56 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Joints: Septic Arthritis S. aureus. Cloxacillin 2 g q6h IV Ceftriaxone 1g q24h IV MRSA suspected / proven give x Rifampicin 600 mg po q24h + 1wk Fusidic acid 500 mg q8h po. OR Cefuroxime 750 mg q8h IV N. gonorrhoea Ceftriaxone 1g q24h IV/ Ceftriaxone 1g q24h IV Arthrotomy may be required to IM x 1d drain pus. + 1 week of parenteral followed by Streptococci Doxycycline 100 mg bid 4-5 weeks oral antibiotic. po x 14d Gram negative cocci are rare. Cefuroxime 750 mg Gram Stain as guide for empirical q8h IV therapy PROSTHETIC JOINT, POST-OPERATION, POST-INTRAARTICULAR INJECTION Staph. epidermidis(CONS), Vancomycin 1 g q12h Linezolid 600 mg q12h Retention of prosthesis associated IV OR po with high Rx failure rate. Removal MRSA Teicoplanin 400 mg of loose prosthesis is q24h IV recommended. + Rifampicin 450 mg q12h po 57 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative MUSCLE

“GAS GANGRENE” Penicillin G 4 MU q4h Ceftriaxone 2gm IV Surgical debridement is primary (contaminated traumatic wound) IV + q12h therapy Clindamycin IV 900 mg q8h Cl. perfringens, other histotoxic Clostridium sp

Necrotising Myofascitis Mixed infection Imipenem 1 g q6h IV Clindamycin 600 mg q8h To consider IVIG 0.4 – 2 g/kg (1-2 OR IV doses) for ﬁrst 72 hours for severe Meropenem 1 g q8h IV + Strep A infection. with coliforms + anaerobes + Ciproﬂoxacin 400 mg Pen G if strep or clostridia Clindamycin 600 mg q8h q12h IV Imipenem or Meropenem if Type 1 – Strep sp Gp A,C and G IV + polymicrobial Vanco if MRSA Type 2 – Clostridial sp. Amp/Sulb 1.5 – 3 g q6h suspected. Type 3 – polymicrobiol IV If strep necrotizing fasciitis, OR reasonable to treat with penicillin (aerobic + anaerobic strep) Pip/Tazo 4.5 g q6h IV & clindamycin If clostridia +/- gas Type 4 – Community associated MRSA gangrene, add clinda to penicillin PYOMYOSITIS Cloxacillin 1g q6h IV Cefazolin 2.0g IV q8h in Surgical drainage important S. aureus, Group A streptococci, MSSA therapy. Add Vanco if MRSA Gm-neg bacilli (rare) 58 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS Recommended Treatment according to DIFFERENT SITE SKIN & SOFT TISSUE INFECTIONS Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative BITE

General Principle Prophylactic antibiotics may be given for a 3- to Treatment aims: The goal of initial therapy is to 5-day course. Meticulous wound care For treatment, antibiotics may be given for a 5- to 7- cover staphylococci, streptococci, day course. Selective wound closure anaerobes, and Pasteurella species. The ﬁrst-line oral therapy is amoxicillin-clavulanate. Selective use of prophylactic High risk bite wound: antibiotics Cat/human For higher risk infections, a ﬁrst dose of intravenous Doxycycline not recommended antibiotic may be given (ie, ampicillin-sulbactam, for children < 8 years and Livestock pregnant woman Monkey bites ticarcillin-clavulanate, piperacillin-tazobactam, or a carbapenem). Deep puncture wounds To treat all infected wounds and Hand/foot wounds to prescribe antibiotics for Bites in immunosuppressed patients high-risk uninfected wounds

Bat Amox/Clav 625 mg q12h Doxycycline 100 mg q12h Streptococcus spp. especially S. anginosus po x 5d po x 5d Staphylococcus aureus Anaerobes, especially Prevotella spp. 59 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS Recommended Treatment according to DIFFERENT SITE SKIN & SOFT TISSUE INFECTIONS Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Cat Amox/Clav 625 mg q12h po Doxycycline 100 mg q12h 80% cat bites become infected. S. aureus, x 5d po x 5d Doxycycline not recommended in Pasteurella multocida (prevalence ~75%) Or children TMP/SMX 160/800 mg q12h x 5d Or Clarithromycin 500 mg po Bartonella henselae Azithromycin 500mg stat q12h x 7d-10d then 250mg q24h x 4d TMP/SMX 160/800 mg Treat immunodeﬁcient patient q12h x 5d with 7- to 10-day course. Cat-scratch fever/disease

Dog Amox/Clav 625 mg q12h Doxycycline 100 mg q12h Only 5% dog bites become infected Viridans strep. P. multocida, S. aureus, po x 5d po x 5d Bacteroides sp., Fusobacterium Plus Metronidazole If severe : 500mg q8h x 5d Imipenem 500 mg q6h IV + Clindamycin 900 mg q6h x 2 weeks Note: Rarely by Capnocytophaga canimorsus present in dog bites. (consider in asplenic /immunosuppressed patient) 60 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS Recommended Treatment according to DIFFERENT SITE SKIN & SOFT TISSUE INFECTIONS Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Human Amox/Clav 625 mg q12h po Penicillin allergy: TMP/SMX Cleaning, irrigation and debride- Viridan strep (100%), S. epidermidis (53%), x 5d 160/800 mg q12h x 5d ment most important. Corynebacterium (41%), S. aureus (29%), Inpatient: IV TMP/SMX plus If severe : Eikenella (15%), Bacteroides (82%), IV clindamycin 150 to 300 Amp/Sulb 1.5g- 3g q6h Peptostrep (26% mg q6h. Mice, Rat, Squirrels or Gerbils Amox/Clav 625 mg q12h po Doxycycline 100 mg q12h Wound injury is usually trivial Spirillum minus (Asia) x 5d po x 5d Untreated infection carries Streptobacillus moniliformis (North America) signiﬁcant mortality Anti rabies treatment IS NOT indicated

Monkeys Acyclovir 800mg q5h Valaciclovir (dose) In South Asia, monkeys are Herpes B virus (5 times daily) x 5d presumed to be at high risk for -Cercopithecine hespesvirus 1 carriage and transmission of rabies, consider anti rabies treatment Case fatality rate 70% with myelitis and hemorrhagic encephalitis

Freshwater fish TMP/SMX 160/800 mg Ciprofloxacin 500mg Aeromonas, streptococci, staphylococci q12h x 5d q12h x5d Saltwater fish Vibrio, Ciprofloxacin 500mg Erysipelothrix rhusiopathiae q12h x5d 61 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative BOILS/ CARBUNCLES

S. aureus Cloxacillin 500mg q6h Erythromycin 500 mg q6h Add fucidic acid 500mg tds in po x 5d po x 5d severe cases. OR Cephalexin 500mg q6h po BURN WOUND SEPSIS Enterobacter sp. S. aureus, Treat according to culture result Important to be guided by culture S. epidermidis,E. coli, result. Initial burn wound care may P. aeruginosa not require antibiotics except local silver sulfadiazine cream 1%. CELLULITIS/ ERYSIPELAS Strep pyogenes, S. aureus (uncommon but diﬃcult Benzylpenicillin (Pen G) Pen G 1-2 MU q6h or Change to oral therapy once pt’s to exclude) 1-2 MU q6h IV + cefazolin 1 g q8h condition improves. Cloxacillin 500 mg q6h IV DECUBITIS ULCERS Polymicrobic Debridement important. Cefuroxime 750 mg Amox/Clav 1.2 g q8h IV Consider MRSA if pt comes from q8h IV + x 10d nursing home. Metronidazole 500 mg OR Rule out osteomyelitis q8h IV Amp/Sulb 1.5 g q8h IV Rx for 7 days 62 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative HERPES ZOSTER Varicella – zoster virus Acyclovir 800 mg 5x/d Valacyclovir 1000 mg IDCP 1995; 4: 293 po x 10d q8h po x 7d In immunocompromised host, give Acyclovir 10-12mg/kg IV (infused 1 hr) q 8h x 7-14

IMPETIGO Group A streptococci, S. aureus Pen V 500mg q6h po Cefuroxime 250 mg q12h AAC 1992; 36 : 1614 + po5d Cloxacillin 500 mg q6h po x 5d INFECTED WOUNDS (Post trauma with sepsis) Polymicrobic: S. aureus, gp A and anaerobic strep, Amox/Clav 1.2 g q8h IV Amp/Sulb 1.5 g q6h IV Wound debridement is Enterobacteriaceae, Cl. perfringens, x10d important.Change to oral drugs Cl. tetan, Pseudomonas (if water exposure) as soon as possible.

Necrotising fasciitis Mixed infections with coliforms, anaerobes Imipenem 1 g q6h IV Amp/sulb 1.5 – 3 g q6h Antimicrobials are usually OR IV OR continued until surgical Meropenem 1 g q8h IV Pip/Tazo 4.5 g q6h IV + debridement is no longer needed. + Clindamycin 600 mg Clindamycin 600 mg q8h IV + q8h IV Ciproﬂoxacin 400 mg q12h IV 63 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

Clindamycin 600 mg Group A Strep To consider IVIG 0.4-2g/kg (1-2) q8h IV doses for ﬁrst 72 hours for severe + Strep A Infection Benzylpenicillin 4 MU q4h IV 64 Chapter 1B Recommended Treatment – different site : SURGICAL AND ORTHOPEDIC INFECTIONS Recommended Treatment According to DIFFERENT SITE VASCULAR Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative CAVERNOUS SINUS THROMBOSIS (P) S. aureus, Cloxacillin 2 g q6h IV Cefuroxime 750mg q8h Use drugs with good CSF Gp A strep, + IV penetration. H. inﬂuenzae, Aspergilius/ Gentamicin 4.5mg/kg + In diabetics with neutropenic, Mucor/ Rhizopus q24h IV Gentamicin 4.5mg/kg consider fungus. q24h IV IV LINE INFECTION (P)

Heparin lock, peripheral lines CIP Cloxacillin 2 g q6h IV Vancomycin 1 g q12h Remove catheter & culture, Change S. epidermidis, AND IV antibiotic according to sensitivity. S. aureus Gram negative org Ceftazidime 1g 24h IV OR Please refer to page 36 for more ( in renal failure) Teicoplanin 6mg/kg/d information on Intravascular IV catheter - Related Infection 65 1C. Recommended Treatment – different site : Tropical Recommended Treatment According to DIFFERENT SITE COMMON TROPICAL BACTERIAL INFECTIONS Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Meliodosis Burkholderia pseudomallei INITIAL: INITIAL: Initial therapy should be given until there Ceftazidime 2 g (120 Imipenem 500 mg q6h is deﬁnite clinical evidence of improve- mg/kg/d) IV q8h x 14d IV ment. Longer treatment duration in with clinical improve- OR critically ill, deep seated abcess, ment Meropenem 1 g q8h IV osteomyelitis etc.

MAINTENANCE: MAINTENANCE: Fever persisting for more than 1 week is TMP-SMX 5mg per kg Amox/Clav 625 mg common and does not imply treatment (TMP component of q12h x 4-6 wk + failure. Bactrim) bd Doxycyline 100 mg Note : 1 TABLET Bactrim 80mg q12h x 20 wk trimethoprim/ 400mg sulfamethoxazole) (for patients allergic to TMP/SMX only) Ex :60 kg Dose : 5mg/kg Trimethoprim

5X60kg=300mg then

300mg/ (80mg TMP of 1 tablet bactrim 66 1C. Recommended Treatment – different site : Tropical Recommended Treatment According to DIFFERENT SITE COMMON TROPICAL BACTERIAL INFECTIONS Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative

(=4 tab bd Bacrtim) Guide : Bactrim Dose < 40kg= 2 tab bd 40-60kg = 3 tab bd >60kg = 4 tab bd

Treatment should be modiﬁed according culture and sensitivity results. Surgical drainage of abscesses should be performed as appropriate 67 1C. Recommended Treatment – different site : Tropical

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Rickettsial disease Scrub typhus, Murine typhus Doxycycline 100 mg Chloramphenicol 500 Chloramphenicol is recommended for Louse-borne, typhus, q12h po x 7d mg q6h po or IV x 7d pregnancy Q fever R. tsutsugamushi R. typhi, R. Prowazekii, Coxiella burnetii Typhoid Fever S. typhi Ciprofloxacin 400 mg Ceftriaxone 2 g q24h IV Use Dexamethasone 3 mg/kg per kg then S. paratyphi A+B+C q12h IV x 14 d (switch x 14 d 1 mg/kg qid for 8 doses afew minutes to po 500 mg q12h as before antibiotic in septic shock Use soon as possible) alternative if suspected or proven OR resistance Chloramphenicol 500 Most S. typhi strains in Malaysia remain mg q6h x 14 d sensitive to Ciprofloxacin, Ceftriaxone & Chloramphenicol Non-Typhoid Fever Salmonella sp. Ciprofloxacin 500 mg q12h po x 10-14 days 68 1C. Recommended Treatment – different site : Tropical

Infection/Possible Organisms Suggested Treatment Comments Preferred Alternative Leptospirosis

L. icterohaemorrhagiae Benzylpenicillin 1.5 MU Ceftriaxone 1 g q12h IV L. canicola q6h IV x 7d x 7d Lyme Disease

Borrelia burgdorferi Doxycycline 100 mg Amoxicillin 500 mg q6h In CNS & cardiac involvement, use q12h po x 2 wk po x2 wk Ceftriaxone 2 g q24h IV for 2-3 weeks

Brucellosis

Brucella sp. Doxycycline 100 mg Doxycycline + Duration of treatment is unclear q12h po x 6 wk + Rifampicin 600 mg Gentamicin 4-6 mg /kg q24h po q24h IV x 2 wk

69 Chapter 2 Recommended Agents based on selected Organisms

ANTIMICROBIAL AGENT BACTERIAL SPECIES ALSO EFFECTIVE RECOMMENDED ALTERNATIVE (CENTS)

Acinetobacter Polymyxin B Up to 70% isolates calcoaceticus- resistant to baumannii complex Imipenem, Meropenem, PIP/TZ Actinomyces israeli Pen G OR Doxycycline Clindamycin, Ampicillin Erythromycin Aeromonas Ciprofloxacin TMP/SMX APAG, imipenem, hydrophila meropenem, ertapenem, Ceph 2, 3, 4, tetracycline Some resistant to carbapenems Bacillus anthracis Ciprofloxacin Doxycycline If susceptible to (anthrax) penicillin, switch to amoxicillin Amox/Clav Bacteroides Metronidazole fragilis OR Clindamycin Bartonella Azithromycin Erythromycin Clarithromycin, azithromycin, (Rochalimaea) OR OR henselae, quintana ciprofloxacin Ciprofloxacin Doxycycline Bordetella pertussis Erythromycin TMP/SMX

Brucella species Doxycycline Doxycycline + (Brucellosis) + Either Rifampicin OR Gentamicin TMP/SMX + OR Gentamicin Streptomycin

Burkholderia Initially IV Then PO In Thailand, pseudomallei Ceftazidime Amox/Clav 12-80% strains OR Imipenem OR TMP/SMX resistant to + Doxy TMP/SMX Campylobacter Erythromycin Fluoroquinolones Clindamycin, jejuni Doxycycline, Azithromycin, Clarithromycin

70 Chapter 2 Recommended Agents based on selected Organisms

Citrobacter species Cefepime Carbapenem For UTI, can use ﬂuroquinolones.

Chlamydia Erythromycin Doxycycline Moxiﬂoxacin pneumoniae OR OR Azithromycin Tetracycline Chlamydia Doxycycline Erythromycin trachomatis OR OR Azithromycin Oﬂoxacin

Chryseobacterium Vancomycin +/- Ciprofloxacin 55% Ciprofloxacin (Elizabethkingia) Rifampicin -resistant meningosepticum In vitro susceptibility may not correlate with clinical efficacy Clostridium difficile Metronidazole Vancomycin (po) (po) Clostridium Pen G Doxycycline Erythromycin, perfringens + Chloramphenicol Clindamycin Clostridium tetani Metronidazole Doxycycline OR Pen G C. Diphtheriae Erythromycin Pen G Rifampicin, Clindamycin Coxiella burnetii Doxycycline Erythromycin (Q fever) acute disease Coxiella burnetii (Cipro OR Doxy) Cipro + Doxy (Q fever) chronic + Rifampicin x 3 years disease Enterobacter Cefepime Ciprofloxacin OR species (aerogenes, cloacae) Imipenem For uncomplicated Enterococcus faecalis Ampicillin Vancomycin UTI, + Nitrofurantoin Gentamicin is effective. High level Gentamicin and Vancomycin resistance increasing

71 Chapter 2 Recommended Agents based on selected Organisms

Enterococcus Linezolid Tygecycline More than 60% faecium, β OR strains are -lactamase +, Streptomycin susceptible to ampicillin high-level & gentamicin. aminoglycoside resistance, vancomycin resistance Escherichia coli Sensitive to Cephalosporins, 37% resistant to APAG, Nitrofurantoin, Amox/Clav Ciprofloxacin; 55% resistant to TMP/SMX. Francisella Streptomycin Doxycycline Chloramphenicol, tularensis OR Ciprofloxacin, (tularemia) Gentamicin Rifampicin Gardnerella vaginalis Metronidazole Clindamycin (bacterial vaginosis) Helicobacter pylori Amoxicillin + Metronidazole Prevalence Clarithromycin pre-treatment resistance increasing. Hemophilus ducreyi Azithromycin Ceftriaxone Most strains (chancroid) OR resistant to Amox/Clav Tetracycline, Amoxycillin, OR TMP/SMX Erythromycin Haemophilus Cefotaxime 30% resistant influenzae Meningitis, OR to Ampicillin Epiglotitis & other Azithromycin, life- threatening Ceftriaxone Clarithromycin illness Amox/Clav Non-life OR threatening Ceph 2 Klebsiella Cephalosporin APAG Antipseudomonal pneumoniae 1,2 OR Penicillin, OR Amp/Sulb Carbapenems Ciprofloxacin OR Amox/Clav Klebsiella Ertapenem Aminoglycoside pneumoniae (ESBL +) Imipenem as adjunct therapy Meropenem Legionella species Fluoroquinolones Clarithromycin TMP/SMX, OR Doxycycline Azithromycin OR Erythromycin Rifampicin

72 Chapter 2 Recommended Agents based on selected Organisms

Leptospira Doxycycline interrogans Pen G

Neisseria Ceftriaxone Spectinomycin High prevalence gonorrhoeae OR OR of fluoroquinolone (gonococcus) Amox/Clav Azithromycin -resistant in Asia. In US, fluoroquinolone is no longer recommended. Neisseria meningitis Pen G Ceftriaxone Cefotaxime (meningococcus Nocardia species TMP/SMX Amox/Clav Amikacin + (Imipenem or Ceftriaxone or Cefuroxime) for brain abscess Pasteurella Pen G Doxycycline Ceftriaxone multocida OR Amox/Clav OR Ceph 2 OR TMP/SMX Proteus mirabilis Amox/Clav TMP/SMX Ciprofloxacin (indole -)

Proteus vulgaris Cefepime APAG (indole +) OR Ciprofloxacin Providencia species Amikacin TMP/SMX Antipseudomonal OR Ceph 3 Penicillin + OR Amikacin, Fluoroquinolones Imipenem Pseudomonas Pip/Tazo Ceftazidime 40% resistant to aeruginosa OR +/- carbapenems Cefepime Aminoglycoside, and 47% resistant +/- Ciprofloxacin, to ciprofloxacin. Aminoglycoside Imipenem, Meropenem Rickettsiae species Doxycycline Chloramphenicol Fluoroquinolones

73 Chapter 2 Recommended Agents based on selected Organisms

Multi drug resistant strains Salmonella typhi Ampicillin Ceftriaxone (Chloramphenicol, OR OR Ampicillin, Ciproﬂoxacin Chloramphenicol TMP/SMX) OR TMP/SMX common in many developing countries Fluoroquinolones not recommended in children Serratia marcescens Cefepime Gentamicin OR Imipenem OR Fluoroquinolones Shigella species TMP/SMX Fluoroquinolones Ampicillin and OR OR TMP/SMX Ampicillin Azithromycin resistant common in middle east and Latin America

Staph. Aureus, Cloxacillin Erythromycin Penicillin methicillin- OR OR (if susceptible) susceptible (MSSA) Flucloxacillin Cephalosporin Clindamycin generation 1 Clarithromycin Health-care Vancomycin Fucidic acid Teicoplanin OR associated OR Linezolid MRSA Rifampicin (preferable in renal failure) (as adjunct therapy) Community- Cotrimoxazole Clindamycin Vancomycin associated MRSA OR OR Teicoplanin Doxycycline Or Linezolid +/- Rifampicin is idndicated for severe infection Coagulase Neg. Vancomycin Teicoplanin Staphylococci +/- OR Fucidic acid Linezolid OR Rifampicin (preferable (as adjunct in renal failure) therapy) Staphylococcus Oral saprophyticus cephalosporins or Amox-clav

74 Chapter 2 Recommended Agents based on selected Organisms

Stenotrophomonas TMP/SMX Cefepime (Xanthomonas, Pseudomonas) maltophilia

Streptococcus, Pen G Erythromycin Doxycycline anaerobic OR (Peptostreptococcus) AM/CL Strep. Pneumoniae Pen G Multiple agents Erythromycin Penicillin-susceptible Vancomycin eﬀective For non- Penicillin-resistant +/- Rifampicin e.g. Amoxycillin meningeal infection Ceph 3, 4 (MIC > 2.0) Streptococcus Pen G All βlactams, pyogenes, OR Erythromycin Group A, B, C, G, F, Penicillin V Strep. Milleri (some add (constellatus, Gentamicin for intermedius, serious Group anginosus) B strep infections) Vibrio cholerae Doxycycline TMP/SMX Strain 0139 is OR resistant to Fluoroquinolones TMP/SMX

Yersinia TMP/SMX Ceph 3 or APAG enterocolitica OR Fluoroquinolones

Yersinia pestis Streptomycin Chloramphenicol (plague) OR OR Gentamicin Doxycycline

75 Chapter 2 Recommended Agents based on selected Organisms

B) RECOMMENDED ANTIFUNGAL AGENTS BASED ON SELECTED ORGANISMS ANTIFUNGAL AGENT ALSO EFFECTIVE FUNGAL SPECIES RECOMMENDED ALTERNATIVE (COMMENTS)

Aspergillus species Voriconazole Echinocandins A. terreus is Amphotericin B Itraconazole resistant to amphotericin B

Candida species Fluconazole Amphotericin B Voriconazole (azole-naïve patient) Echinocandins

Candida species Amphotericin B Echinocandins Azoles can still (azole-exposed be used if patient) organism is found to be susceptible C. albicans ﬂuconazole Amphotericin B Voriconazole Echinocandins C. glabrata Amphotericin B Echinocandins High-dose Voriconazole ﬂuconazole

C. krusei Amphotericin B Echinocandins C. krusei is Voriconazole inherently resistant to ﬂuconazole C. parapsilosis High-dose Amphotericin B C. parapsilosis ﬂuconazole Voriconazole has reduced susceptibility to echinocandins

C. tropicalis Amphotericin B High-dose Echinocandins ﬂuconazole Voriconazole

Other non-albicans High-dose Amphotericin B Voriconazole Candida species fluconazole Echinocandins Cryptococcus species Amphotericin Fluconazole Itraconazole B +/- flucytosine is less effective than fluconazole Dermatophytes – Terbinafine Griseofulvin Itraconazole e.g. Trichophyton, Fluconazole Microsporum & Epidermophyton spp.

Fusarium species Amphotericin B Voriconazole Posaconazole

76 Chapter 2 Recommended Agents based on selected Organisms

B) RECOMMENDED ANTIFUNGAL AGENTS BASED ON SELECTED ORGANISMS

Histoplasma species Amphotericin B Itraconazole

Penicillium Amphotericin B Itraconazole marneﬀei

Scedosporium Voriconazole Posaconazole Resistant to +/- Terbinaﬁne many drugs species including amphotericinb

Sporothrix species Amphotericin B Itraconazole

Zygomycetes – e.g. Amphotericin B Posaconazole Rhizopus, Mucor & Absidia spp.

77 C: COMPARISON OF ANTIMICROBIAL SPECTRA AMONG COMMON CLINICAL ISOLATES Abbreviations: + > 60% susceptible V 30-60% antibiotic susceptible 0 <30% susceptible S synergistic when used with a beta-lactam Clindamycin Mupirocin Teicoplanin Rifampicin Vancomycin Cotrimoxazole Nitrofurantoin Fusidic Acid Ciproﬂoxacin Erythromycin Gentamicin Cloxacillin Penicillin Chloramphenicol Methicillin Susceptible S. aureus + + + + + 0 + + + + + + Methicillin Resistant S. aureus + 0 0 + + + + 0 + Coagulase-negative staphylococci + v v v v 0 ++++++++

Streptococcus species Bacitracin Cefuroxime Erytromycin Augmentin Cefotaxime Ampicillin Gentamicin Penicillin Vancomycin Teicoplanin Piperacillin /Tazobactam Chloramphenicol Nitrofurantoin Streptococcus species + S + + + Streptococcus agalactiae (Group B Strep) + S + + + Streptococcus pneumoniae v + + + + Enterococcus faecalis + + + + + + Enterococcus faecium + + + + + + Enterococcus species + + +++ + + 78 C: COMPARISON OF ANTIMICROBIAL SPECTRA AMONG COMMON CLINICAL ISOLATES Amikacin Cefepime Ampicillin Ceftazidime Augmentin Cefuroxime Ciproﬂoxacin Ampicillin Imipenem Cefotaxime Meropenem Piperacillin / Tazobactam Cefoperazone/ Sulbactam B Polymyxin Netimicin Cephalexin Cotrimoxazole Sulbactam Gentamicin

Acinetobacter 0 0 VV 0 V 0 V V V V V V + 0 V Enterobacter VV + + 0 + 0 + Escherichia coli + + + + V V V Klebsiella + + + 0 + + Proteus + + + + V V V ESBL 0 0 0 0 0 + 0 + 0 0 + 0 0 Amp-C Producer + + + + e Amikacin Cefepime Imipenem Ceftazidime Piperacillin/ Piperacillin/ Tazobactam Meropenem B Polymyxin Ciproﬂoxacin Gentamicin Cotrimoxazol Cefoperazone/ Cefoperazone/ Sulbactam Pseudomonas species + + + + V + + + + + + Pseudomonas aeruginosa + + V V V + + + + + 0 Burkholderia cepacia + + + Stenotrophomonas maltophilia + 0 + 79 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

CHAPTER 3a: TREATMENT OF HIV INFECTIONS SELECTION OF ANTIRETROVIRAL TREATMENT The guiding principle for selecting antiretroviral therapy is the need for treatment regimens that provide maximum potency and a sustained, durable antiviral response.

However, the panel strongly advocates against the usage of any suboptimal antiretroviral regimens (including monotherapies and dual nucleoside regimens) as research data unequivocally demonstrates the selection of resistant viral strains with these regimens, which in turn, leads to treatment failure.

At present the antiretroviral drugs that are available in Malaysia include:

I. Nucleoside reverse transcriptase inhibitors (NRTI)

Zidovudine (AZT/ Retrovir) 300 mg q12h Didanosine (ddl/ Videx) 200 mg q12h or 400 mg q24h (>60 kg) OR 300 mg q24h od (<60kg) OR Videx EC 400 mg OM (if >60 kg) OR 250 mg q24h (<60 kg) Lamivudine (3TC/ Epivir 150 mg q12h Stavudine (d4T/ Zerit) 30 mg q12h Combivir (AZT + 3TC) 1 tab q12h Tenofovir-Emtricitabine (Tenvir-Em) (300mg-200mg) 1 tab od II. Non – nucleoside reverse transcriptase inhibitors (NNRTI)

Efavirenz (Stocrin) 600 mg ON po Nevirapine (Viramune) 200 mg q24h po x 2wks then 200 mg q12h

81 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

III. Protease inhibitors (PI)

Indinavir (Crixivan) 400 - 800 mg q12h + Ritonavir 100 mg q12h Ritonavir (Norvir) 600 mg q12h or 100 mg q12h when in combination with Indinavir Kaletra (Lopinavir 133 mg+ Ritonavir 33 mg) 3 tab q12h Kaletra (400mg lopinavir + 100mg ritonavir) 2 tab q12h Combination drugs - SLN (30 mg) (d4T/3TC/Nevirapine) 1 tab q12h COMMENCING ANTIRETROVIRAL THERAPY – WHEN TO START Summary of recommendations on when antiretroviral therapy should be started

Clinical Category CD4 Count Viral Load Viral Load

Symptomatic Any value Any value Treat AIDS deﬁning illness Severe symptoms*

Asymptomatic <200/mm3 Any value Treat Asymptomatic >200 but <350/mm3 Any value Treatment recommended Asymptomatic >350/mm3 >50,000** Hepatitis B-C coinfection, copies/ml HIVAN, Pregnant,Cardiovascular disease 82 *Examples include but not limited to Candidiasis, vulvovaginal: persistent > 1 month, poorly responsive to treatment Candidiasis, oropharyngeal Herpes Zoster: more than 1 episode, or involving more than 1 dermatome Cervical dysplasia, severe or Carcinoma in situ Constitutional symptoms e.g., fever (> 38.5°C) or diarrhoea more than 1 month

The above must be attributed to HIV infection or have clinical course or management complicated by HIV ** WHO recommendation is in MIU/ml – 2 million copies/ml = 800,000MlU/ml

# Some experts recommend initiating treatment since the 3-year risk of developing AIDS in untreated patients is > 30%. 83 OR Efavirenz Nevirapine Raltegravir Efavirenz Nevirapine COLUMN B(NNRTI) COLUMN tab q12h if Efavirenz used q12h if Efavirenz tab Kaletra 2 tab q12h or Kaletra 4 Kaletra q12h or 2 tab Kaletra PI Based Regime 800 mg q12h + Indinavir 100 mg q12h Ritonavir Zidovudine + Lamivudine Zidovudine Lamivudine + Stavudine q12h Combivir 1 tab + emtricitabine Tenofovir Lamivudine + Didanosine + Didanosine Zidovudine COLUMN A (NRTI) COLUMN (New NRTI or NNRTI not used not or NNRTI NRTI (New before) + Zidovudine Stavudine Didanosine + Stavudine COMMENCING ANTIRETROVIRAL THERAPY – WHAT TO START WITH START TO – WHAT THERAPY ANTIRETROVIRAL COMMENCING Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Antiretroviral therapy comprises of one choice each from Column A and B. Drugs are listed in a priority order a priority in listed Column A and Drugs are B. each from one choice of comprises therapy Antiretroviral Not recommended If failure of the above regime of the above If failure Recommended as alternative Recommended Strongly recommended Strongly 84 COMMENTS / REFERENCE COMMENTS The efficacy of high dose Acyclovir and Valacyclovir and Valacyclovir Acyclovir of high dose The efficacy conclu- has not been CMV infection in preventing sive. for high risk well established is approach Preemptive prophylaxis. over and preferred HSCT recipients has also been used in SOT approach Preemptive PCR or Ag) is surveillance Close CMV (by recipients Main Rx outcome in ensuring a successful essential is myelotoxicity; of Ganciclovir effect adverse nephrotoxicity Foscarnet: : Non Formulary * Foscarnet or *Foscarnet 90 -180 *Foscarnet with GCV intolerant , with GCV intolerant Valacyclovir 1.5 q12h 1.5 Valacyclovir or pts with cytopenia) or pts q8h, then Acyclovir PO q8h, then Acyclovir 800mg 6h x 6 months ; 6 months 800mg 6h x mg/kg/d pts in BD (For alternative: Ganciclovir Ganciclovir alternative: IV Acyclovir 500mg/m2IV Acyclovir failure/resistance cases cases failure/resistance SUGGESTED REGIMEN SUGGESTED CHAPTER 3b: VIRAL INFECTIONS 3b: VIRAL CHAPTER PRIMARY ALTERNATIVE I. Prophylaxis - PO 450 Valganciclovir x from 900 mg q24h to 3-6 engraftment HSCT; for months 900 mg q24h (initiate for within 10 days) renal post 100-200 days transplant. of the (Modification dose needed for allograft renal impaired function) Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter INFECTING ORGANISM INFECTING CytoMegaloVirus (CMV) infection infection (CMV) CytoMegaloVirus host in immunocompromised HIV recipients, SOT (HSCT, patients) Strongly recommended Strongly 85 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

CHAPTER 3b: VIRAL INFECTIONS Infecting Organism Suggested Regimen Comments / Reference Primary Alternative II. Preemptive Rx(CMV PCR +): Valganciclovir PO 900 mg q12 Dose modiﬁcation for ganciclovir, foscarnet and or acyclovir for renal impaired patients based on A. Induction therapy: *Foscarnet 90 mg/kg q12 Creatinine clearance Renal impairment Valganciclovir PO 450 - 900 mg q12h; or Ganciclovir IV: 5 -10 Seminar in Hematology 2009;46: 230-47 Int J mg/kg in BD (1h inf) . Review Hematol; 2010; 91: 588-95. & Adjust dose weekly according to viral load until viral load declines B. Maintenance therapy Valganciclovir PO 450 - 900 mg q24h; or Ganciclovir IV: 5 mg/kg q24h until CMV PCR negative III. Targeted Rx (Active CMV disease): A. Induction Rx: IV Ganciclo- vir: 5 mg/kg q12h until 2-3 wks and or clinical improvement B. Maintenance Rx: Ganciclovir IV: 5 mg/kg 86 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

Infecting Organism Suggested Regimen Comments / Reference Primary Alternative Varicella Zoster Virus I. Prophylaxis Acyclovir Valacyclovir PO 500mg q12h For patients with with hematological malignancies infection (VZV) PO 400mg q8h x3-6 mo in and bone marrow failures and patients with severe post -HSCT, Valacyclovir PO 1g q8h infection, IV acyclovir is preferred for Rx of VZV in immunocompromised host Acyclovir PO 200mg q12h x 6 (HSCT, SOT recipients, HIV mo post-renal transplant *Famciclovir PO 500mg q8h * For immunocompromised patient who had patients) *Human VZIG IM 1.25 ml (1 signiﬁcant exposure and no previous history of vial or 125 IU) for every 10 kg varicella Duration: Immunocompetent: 5-5-10d; body wt. Max dose = 6 ml ophtalmicus: 10d II. Targeted Rx Seminar in Hematology 2009;46: 230-47 Acyclovir IV 10-12mg/kg (1h inf) q8h or 500 mg/m2 q8h x 7-14d; CNS infection: 14-21d Or Acyclovir PO 800mg 5x/day x 10 days Herpes Simplex Virus I. Prophylaxis Acyclovir PO PO Valacyclovir 500mg q12h For patients with with hematological malignancies infection 400mg q8h x3-6 mo in post and bone marrow failures and patients with severe -HSCT, Acyclovir PO 200mg PO Valacyclovir 500 q8h infection, IV Acyclovir is preferred for Rx of VZV in immunocompromised host q12h x 6 mo post-renal (HSCT, SOT recipients, HIV transplant *Famciclovir PO 250mg q8h Duration: keratitis, stomatitis: 7 days, vaginitis: 5 patients) days II. Targeted Rx Acyclovir IV 10mg/kg q8h or 500 mg/m2 Topical acyclovir is of no beneﬁt for Herpetic q8h x 7-14d; CNS infection: stomatitis Seminar in Hematology 2009;46: 230-47 14-21d Or Acyclovir PO 400mg 5x/day x 10 days 87 Comments / Reference Comments Indication: Indication: high ALT - persistent DNA HBs Ag & HBV - detectable bx on liver - hepatitis IV formulation is not registered in Malaysia registered is not IV formulation or within of exposure 12hrs within Give prophylaxis neonate for 48hr post-delivery Alternative Lamivudine (3TC) 100 mg Lamivudine (3TC) q24h po Fanciclovir 500 mg q8h po + OR ( If on Peg Interferon : Interferon ( If on Peg (Pegasys ® 180 mcg SC 1x/week (Pegasys Suggested Regimen Suggested (Peg-Intron ®) 1.5 mcg/kg SC 1x/week (Peg-Intron Ribavirin 400mg am ; 600mg pm po Ribavirin a) Alfa-2a Interferon alfa x 3 MIU sc x 3 wks x 24 wks wks x 24 MIU sc x 3 wks x 3 alfa Interferon Alfa-2b Primary b) Interferon alfa 5 million 5 million alfa Interferon units q24h SC x 4-6 mths Hepatitis B immune globulin (200iu/ml) B immune Hepatitis : 0.5ml Perinatal IM : 1.0ml IM Percutaneous : 1.0ml IM Sexual Ribavirin 2 g IV stat then 1 g q6h x 4d then 0.5g q8h x 6d 1 g q6h x 4d then 0.5g then IV stat 2 g Ribavirin Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Infecting Organism Infecting Hepatitis C Hepatitis Chronic hepatitis Chronic HEPATITIS VIRUS HEPATITIS prophylaxis Post-exposure HAEMORRHAGIC VIRAL FEVER HAEMORRHAGIC Hantavirus

88 Comments / Reference Comments Cryotherapy or electrocautery also Cryotherapy or electrocautery eﬀective Consider HPV vaccination. HPV Consider eﬀective For chronic suppression use For 400 mg q12h po Acyclovir Use IV in ill and/or and immuno- Use IV in ill and/or within Start pts. compromised 24hrs of rash days times/wk q8h IV x 10d q8h IV x 10d Alternative Patient-administered: Patient-administered: Imiquimod 5% sachets sachets Imiquimod 5% Acyclovir 10 – 12 mg/kg 10 – 12 mg/kg Acyclovir Acyclovir 10 – 12 mg/kg 10 – 12 mg/kg Acyclovir Acyclovir 400 mg q8h 7 – 10 Acyclovir [Aldara®] ( non formulary) 3 formulary) [Aldara®] ( non Suggested Regimen Suggested 7d 5d 10d 10d + 14-21d Primary Doctor- administered: administered: Doctor- Consult Dermatologist q12h for total 10 days. total q12h for (slow 1 hr infusion) IV x (slow Acyclovir 10 mg/kg q8h 10 mg/kg Acyclovir Prednisolone 30 mg q12h Prednisolone 30 mg q12h po x 5d then taper to 5 mg to po x 5d then taper Acyclovir 400 mg 5x/d po x Acyclovir 800 mg 5x/d po x Acyclovir Trichloroacetic Acid ( TCA) : Acid ( Trichloroacetic Acyclovir 200 mg/5x/d po x Acyclovir 200 mg/5x/d po x Acyclovir Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Infecting Organism Infecting trimester, trimester, rd

PAPILLOMA VIRUS (WARTS) VIRUS PAPILLOMA Varicella (chicken pox) (chicken Varicella adults, pneumonia, Young 3 immunocompromised HUMAN HERPES VIRUSES HUMAN HERPES Herpes simplex Bell's palsy Gingivostomatitis Genital Encephalitis

89 Comments / Reference Comments and treat for 7-14 days 7-14 and treat for Use IV in immunocompromised pts pts Use IV in immunocompromised IV formulation is not registered in is not registered IV formulation Malaysia q8h IV x 7-10d Alternative inhalation x 5days Acyclovir 10 – 12 mg/kg 10 – 12 mg/kg Acyclovir Zanamivir 10 mg q12h by 10 mg q12h by Zanamivir Suggested Regimen Suggested x 4d then 0.5g q8h x 6d x 5-7d 5days Oseltamivir 75 mg q12h po x 5days Oseltamivir Ribavirin 2 g IV stat then 1g q6h Ribavirin 2 g IV stat Primary Therapy remains predominantly supportive care. supportive predominantly remains Therapy Acyclovir 800 mg 5x/d po x Acyclovir Oseltamivir 75 mg q12h po Oseltamivir Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Infecting Organism Infecting Zoster SARS CoV SARS NIPAH VIRUS NIPAH Encephalitis AVIAN (H5N1) INFLUENZA AVIAN INFLUENZA VIRUS A&B INFLUENZA

90 Comments Add Pyridoxine 10 mg q24h Add Pyridoxine is and AKURIT po AKURIT-4 maintenance for available : Indications therapy of maintenance Treatment pulmonary and phase for tuberculosis. extrapulmonary ( Isoniazid 75mg + Akurit-4 150mg + Rifampicin 400mg + Pyrazinamide Tab): 275mg Ethambutol 2 months. phase for Intensive 75mg + ( Isoniazid Akurit : 150mg Tab) Rifampicin 4 phase for Maintenance / 15kg Dose : 1 tab months. body weight * maintenance therapy therapy * maintenance to be given for 4 months. for be given to INH + RIF q24h or 2-3x /wk INH + RIF q24h Continuation Phase Of Therapy Continuation Suggested Regimens Suggested + + + OR IM Adult Primary 2 months be given for for be given INH 5 mg/kg RIF 10 mg/kg (max 2 g) q24h (max (max 1 g) q24h (max (max 1.2g) q24h (max ETB 15-20 mg/kg PZA 20-30 mg/kgPZA *initial therapy to *initial therapy SM 15 mg/kg/day (max 300 mg) q24h (max 600 mg) q24h (max CHAPTER 3c: MYCOBACTERIAL INFECTIONS MYCOBACTERIAL 3c: CHAPTER Modifying Circumstances Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Causative Agent/disease Causative Mycobacterium tuberculosis tuberculosis Mycobacterium Pulmonary TB 91 unknown Comments ATS Consensus: ATS AJRCCM 1997; 152: 5 Durations of treatment of treatment Durations Add Pyridoxine 10 mg q24h Add Pyridoxine Refer to dosage above dosage to Refer contraindicated Streptomycin in pregnancy Add Pyridoxine 10 mg q24h Add Pyridoxine 12 months. po Rx for 0.2 mg/kg Dexamethasone x 1 month IV/po for ETB not recommended children Standard TB treatment applies. TB treatment Standard INH + RIF q24h or INH + RIF q24h or 2-3x/ * maintenance therapy therapy * maintenance to be given for 4 months. 4 for be given to week x 4 months or more x 4 months week 2-3 x/week for 4 months or 4 months for 2-3 x/week INH + RIF q24h or 2-3x /wk INH + RIF q24h Continuation Phase Of Therapy Continuation Suggested Regimens Suggested Adult + ETB Primary +ETB q24h x 2 months INH + RIF + ETB INH + RIF + PZA INH + RIF + PZA INH + RIF + PZA INH + RIF + PZA q24h x 2 months q24h x 2 months q24h x 2 months INH + RIF + PZA +ETB INH + RIF + PZA CHAPTER 3c: MYCOBACTERIAL INFECTIONS MYCOBACTERIAL 3c: CHAPTER Modifying Pulmonary Circumstances TB meningitis Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Causative Agent/disease Causative Other Mycobacterial Diseases Other Mycobacterial M. bovis TB & AIDS TB during pregnancy TB during pregnancy Extrapulmonary TB Extrapulmonary 92 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

CHAPTER 3c: MYCOBACTERIAL INFECTIONS

Causative Agent/disease Suggested Regimens Modifying Comments Circumstances Primary Continuation Phase Of Therapy MAI Immunocompetent Adult Continue treatment May add Streptomycin or ETB (15 mg/kg po) + for up to 24 months. Amikacin 15 mg/kg 3 Clarithromycin times/week for 2-6 months in 500 mg q12h severe cases. po + Treatment also involves Rifampicin excision of aﬀected lymph 10 mg/kg/day nodes (max 600 mg) Rx with INH + RIF + PZA is usually unhelpful even if sensitive in vitro testing HIV / AIDs Clarithromycin Clarithromycin + 500 mg ETB (15 mg/kg/d) for life long q12h po + ETB 15-25 mg/kg/d + Rifabutin 300 mg od po + one or more of Ciproﬂoxacin 750 mg q12h po, Amikacin 7.5 – 15 mg/kg q24h po 93 Comments Treat for at least 12 months 12 months least at for Treat or sputum culture of negative 18 months. up to In children use same regimen use same regimen In children MAI above. as for 4-6 wks for Treat Surgical excision useful excision Surgical OR Rif 600 mg /kg/day INH 300 mg + Rif 600 mg q24h + ETB 15 mg/kg q24h + q24h + Strep 15 mg/kg/dq24h + Strep + Cycloserine 250 mg q12h + Cycloserine Rifampicin 600 mg monthly Rifampicin Continuation Phase Of Therapy Phase Continuation RIF 600 mg q24h + Strep 15 mg RIF 600 mg q24h + Strep Amikacin 7.5 mg/kgAmikacin IM q12h OR TMP/SMX q8h po TMP/SMX Suggested Regimens Suggested Surgery kg q24h) 500 mg Primary 6 months q12h po x ETB (15 mg/ RIF (600 mg) + INH (300 mg) + Clarithromycin Clarithromycin Surgical excision. Surgical Dapsone 100 mg Dapsone q24h 50 mg Clofazimine q24h x 1 year CHAPTER 3c: MYCOBACTERIAL INFECTIONS MYCOBACTERIAL 3c: CHAPTER Modifying Tuberculoid/ Circumstances indeterminate indeterminate (smear negative) Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Causative Agent/disease Causative Mycobacterium leprae Mycobacterium M. ulcerans M. scrofulaceum M. kansasii M. chelonae 94 Comments + q24h monthly q24h x 3 years MAINTENANCE Dapsone 100 mg Dapsone Clofazimine 50 mg 50 Clofazimine RIfampicin 600 mg 600 mg RIfampicin Clofazimine 300 mg 300 Clofazimine Continuation Phase Of Therapy Phase Continuation Suggested Regimens Suggested + + x 3 wks q24h po q24h po Primary Dapsone 100 mg Dapsone INTENSIVE PHASE Clofazimine 50 mg Clofazimine RIF 600 mg q24h po CHAPTER 3c: MYCOBACTERIAL INFECTIONS MYCOBACTERIAL 3c: CHAPTER Modifying Circumstances /borderline /borderline Lepromatous (smear positive) Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Causative Agent/disease Causative

95 Comments / Reference Comments st Metronidazole: Contraindicated in Contraindicated Metronidazole: 1 trimester dose 15 mg/kg then stat One bd for 7 days One bd for Alternative q8h po x 5d Paediatric q8h po x 5d Paediatric Metronidazole 750 mg Metronidazole TMP-SMX – dapsone – dapsone TMP-SMX 7.5 mg/kg 5d in 3 doses x Suggested Regimen Suggested CHAPTER 3d: PARASITE INFECTIONS PARASITE 3d: CHAPTER po x 10d q12h x 10d Primary Paediatric dose Paediatric Paediatric dose Paediatric mg q12h x 7-10d daily X 10days or daily X 10days 15 mg/kg then stat TMP/SMX (160/800) TMP/SMX 750mg tds for 10 days 10 days for 750mg tds 2 mg/kg/dose 2 g) (max. 7.5 mg/kg 5d in 3 doses x Doxycycline 100 mg q12h Doxycycline Metronidazole 1.5g po once Metronidazole Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic Cyclospora Blastocystis infection Blastocystis Balantidium coli Balantidium PROTOZOA – INTESTINAL PROTOZOA 96 Comments / Reference Comments Metronidazole NOT effective in cysts in cysts effective NOT Metronidazole 500 mg q8h x 10 d) passer (use #Diloxanide It is self-limiting, in severe cases consider cases in severe It is self-limiting, medications Alternative mg q6h x 10d Tetracycline 500 Tetracycline Spiramycin 50-100 Spiramycin mg/kg in 3 doses x 12d Tinidazole 1g q12h po x 3d 1g q12h *Tinidazole po x 5d 1g q12h *Tinidazole Suggested Regimen Suggested q12h Primary mg/d x 27d q8h po x 10d mg q8h po x 10d CHAPTER 3d: PARASITE INFECTIONS PARASITE 3d: CHAPTER po x 1d, then 1250 Azithromycin 1250 mg 1250 mg Azithromycin Metronidazole 400-800 400-800 Metronidazole Metronidazole 800 mg Metronidazole Mild to moderate: Mild to 400-800 mg Metronidazole q8h po x 7-10d Severe: 800 mg q8h Metronidazole po x 7-10d dose Paediatric 35-50 mg/kg/d in 3 doses x 7-10d Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic Hepatic abscess Hepatic Dientamoebiasis Dientamoebiasis infection) fragilis (Dientamoea Cryptosporidium parvumCryptosporidium Entamoeba histolytica histolytica Entamoeba diarrhoea Dysenteric/ 97 Comments / Reference Comments in AIDS 2 tab 3x/wk in AIDS 2 tab Chronic suppression required required suppression Chronic *NF item Consider drainage for abscess for Consider drainage 250 mg add Chloroquine to Recommended in Malaysia # Drug not available q12h x 2wk x 7d Alternative 50-75 mg/day #Paromomycin #Paromomycin Pyrimethamine Pyrimethamine 650 mg q8h x 21d 650 mg q8h q6h po x 10d 14 d then 25 mg q6h po as maintenance dosage as maintenance *Tinidazole 2 g once po 2 g once *Tinidazole dose Paediatric 50 mg/kg once OR 400mg Albendazole q24h po x 5d 25-35 mg/kg/d in 3 doses #Di-iodohydroxyquinoline #Di-iodohydroxyquinoline + Folinic acid 10-25mg/day, acid 10-25mg/day, + Folinic Suggested Regimen Suggested Primary q8h x 10d if AIDS pt; if AIDS pt; to 4 weeks to X 7-10 days, X 7-10 days, TMP-SMX –DS 1 bd TMP-SMX #Diloxanide 500 mg #Diloxanide TMP-SMX –DS qid up TMP-SMX Metronidazole 200mg Metronidazole q8h po x 5d dose Paediatric 15 mg/kg then stat 7.5 mg/kg q8h po x 5d CHAPTER 3d: PARASITE INFECTIONS PARASITE 3d: CHAPTER Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic Isospora belli Giardia lamblia Cyst passers (carriers) passers Cyst 98 Highly toxic beneficial effects beneficial contraindicated For For contraindicated Comments / Reference Comments gradually increased to to increased gradually 0.5 mg until CSF is clear 0.5 mg until ophthalmologist review ophthalmologist Amphotericin B 0.1 mg, Amphotericin Antimony stibogluconate stibogluconate Antimony Topical corticosteroids are are corticosteroids Topical Co-trimoxazole may have some have may Co-trimoxazole If IV response is poor, give intrathecal give is poor, If IV response (the choice) is NOT available in Malaysia available (the choice) is NOT 3x/wk IV q8h po x 2wk B 2 mg/kg od Liposomal Ampho Alternative Metronidazole 400 mg Metronidazole or IM x 15-25 doses + Pentamidine 4 mg/kg Pentamidine Suggested Regimen Suggested q24h IV x q8h po x 7d mg/kg/d IV, mg/kg/d IV, Primary q12h po x wk Quinine 650 mg Amphotericin B 1 Amphotericin uncertain duration uncertain Topical application: Topical 14 doses up 20 days and Neosporin x 3-4wk Albendazole 400mg Albendazole 600 mg q8h po x 7-10d + Propamidine isethionate isethionate Propamidine Amphotericin B 0.5mg /kg Amphotericin Miconazole nitrate 1%, 0.1% 1%, nitrate Miconazole Clindamycin 1.2 g q12h IV or Clindamycin Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic Leishmania donovani Babesia sp Amoebic meningoencephalitis Amoebic meningoencephalitis sp) (Naegleria sp, Acanthamoeba Acanthamoeba keratitis Acanthamoeba PROTOZOA - EXTRAINTESTINAL PROTOZOA Microsporidium

99 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

Suggested Regimen Anatomic Site / Diagnosis Comments / Reference Primary Alternative Toxoplasmosis Pyrimethamine 25-100 mg/d Spiramycin 3-4 g/d x 3wk Spiramycin is suitable for pregnant x 3-4wk + Paediatric dose: mothers, it is not teratogenic. Sulfadiazine 1-1.5 g q6h 50-100 mg/kg/d x 3-4wk x 3-4wk + Folinic acid 10 mg/d x 3-4wk Pneumocystis jiroveci (Pneumocystis carinii) pneumonia Please refer to Chapter 4 Treatment of Opportunistic Infections Toxoplasma gondii (Encephalitis)

Metronidazole 2 g po once *Tinidazole 2 g stat Treat male sexual partner with same Trichomonas vaginalis drug or 500 mg q12h x 7d po OR 500 mg q12h Metronidazole is contraindicated in 1 st trimester NEMATODES - INTESTINAL < 2 years; do not administer Ascaris lumbricoides Albendazole 400 mg po x 3d *Mebendazole 100 Albendazole and Mebendazole (<2years: Pyrantel mg q12h po x 3d pamoate 11mg/kg po x 1d) 100 Comments / Reference Comments Treat the whole family family the whole Treat *NF item Mebendazole in vanishing cream Mebendazole po x 3d daily x 1-2d OR mg/kg/d x 3d mg/kg/d po x 3d Ivermectin Alternative #Tiabendazole 50-100 #Tiabendazole #Ivermectin 200 ug/kg #Ivermectin 200 ug/kg Albendazole 400 mg Albendazole #Thiabendazole (topical) #Thiabendazole 200mcg/kg per day X2 days 200mcg/kg *Mebendazole 100 mg q12h *Mebendazole *Mebendazole 100 mg q12h *Mebendazole po x 3d 11 mg/kg pamoate *Pyrantel po once Albendazole 400mg once po; once 400mg Albendazole repeat in 2wk po x mg once 100 *Mebendazole 2wk 3d; repeat in Suggested Regimen Suggested Primary q12h po x 3d q24h bd po x 3d Albendazole 400 mg Albendazole Metronidazole 2 g po once 2 g po once Metronidazole x 7d or 500 mg q12h *Mebendazole 100 mg *Mebendazole Albendazole 400mg po x 1d Albendazole Albendazole 400 mg po x 3d Albendazole Metronidazole 250 mg Metronidazole q8h X 10d Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic Enterobius vermicularis Enterobius Trichuris trichiura Trichuris Strongyloides stercoralis Ancylostoma braziliense Ancylostoma larva migrans) (cutaneous Hookworm infection Hookworm infection americanus, (Necator duodenale) Ancylostoma Dracunculiasis (Dracunculus medinensis) NEMATODES EXTRAINTESTINAL NEMATODES 101 q8h po x 5d Comments / Reference Comments require current adjunctive steroid adjunctive require current Concomitant prednisolone 10 mg Concomitant Drug will clear only microfilaria but only microfilaria Drug will clear adult worms NOT use Ivermectin In pregnancy : Adult worm 100 mg q12h x 6 weeks Doxycycline Severe lung, heart & CNS disease may Severe q12h x 5d mg q12h x 5d Alternative *Mebendazole 100-200 *Mebendazole *Mebendazole 100-200 mg *Mebendazole Diethylcarbamazine : D1 & D2 : Diethylcarbamazine : 100 mg 50 mg q8h D3 q8h : 2 mg/kg q8h D4 – D14 Suggested Regimen Suggested Primary q8h po x 1d po x 8-14d single dose q12h po x 5d Paediatric dose: Paediatric Microfilaremia po single dose + po single dose Paediatric dose: Paediatric Same as adult dose Albendazole 400mg Albendazole Same as adult dose Albendazole 400 mg 400 mg Albendazole #Praziquantel 25mg/kg 25mg/kg #Praziquantel Albendazole 400mg q12h Albendazole #Ivermectin 200-400 mcg/kg 200-400 mcg/kg #Ivermectin Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic Filariasis (Elephantiasis) Paragonimus wastermani Paragonimus Clonorchis sinensis hepatica Fasciola buski Fasciolopsis viverrini Opisthorchis Trichinellosis Trichinellosis spiralis) (Trichinella (FLUKES) TREMATODES Toxocariasis Toxocariasis larva(visceral migrans) 102 q8h po x 5d Comments / Reference Comments Mebendazole in vanishing cream in vanishing Mebendazole Concomitant prednisolone 10 mg Concomitant Severe lung, heart & CNS disease may Severe steroid adjunctive require current Drug will clear only microfilaria but Drug will clear only microfilaria adult worms NOT In pregnancy use Ivermectin Adult worm : q12h x 6 weeks 100 mg Doxycycline q12h x 5d mg q12h x 5d mg/kg/d x 3d mg/kg/d Alternative #Thiabendazole (topical) #Thiabendazole *Mebendazole 100-200 *Mebendazole #Tiabendazole 50-100 50-100 #Tiabendazole Diethylcarbamazine : Diethylcarbamazine D1 & D2 : 50 mg q8h D3 : 100 mg q8h q8h D4 – D14 : 2 mg/kg *Mebendazole 100-200 mg *Mebendazole #Ivermectin 200 ug/kg daily x 1-2d 200 ug/kg #Ivermectin Suggested Regimen Suggested Primary po x 8-14d q12h po x 5d q8h X 10d Paediatric dose: Paediatric Same as adult dose Albendazole 400mg Albendazole Albendazole 400mg q12h Albendazole Metronidazole 250 mg 250 Metronidazole Albendazole 400 mg po x 3d 400 mg Albendazole Microfilaremia #Ivermectin 200-400 mcg/kg po single dose + 400 mg Albendazole single dose Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic Ancylostoma braziliense braziliense Ancylostoma larva migrans) (cutaneous Trichinellosis Trichinellosis spiralis) (Trichinella Toxocariasis Toxocariasis larva(visceral migrans) Filariasis (Elephantiasis) Dracunculiasis (Dracunculus medinensis) NEMATODES EXTRAINTESTINAL NEMATODES 103 Comments / Reference Comments Repeat Albendazole for 3 cycles with for Albendazole Repeat cycles. between 14days rest Alternative + Suggested Regimen Suggested Surgical drainage of cyst Surgical Albendazole 400mg q12h po x 28d 400mg q12h po x 28d Albendazole #Praziquantel 40 mg/kg/d in 2 doses x 1d in 2 doses 40 mg/kg/d #Praziquantel x 1d in 3 doses 60 mg/kg/d #Praziquantel Primary q8h po x 1d Paediatric dose: dose: Paediatric Same as adult dose Same as adult #Praziquantel 25mg/kg 25mg/kg #Praziquantel #Praziquantel 10mg/kg 10mg/kg #Praziquantel po once Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic CESTODES tapeworms Intestinal latum D. saginata T. solium T. caninum D. Echinococcus granulosus Echinococcus disease) (hydatid Schistosomiasis japonicum Schistosomiasis Schistosomiasis haematobium haematobium Schistosomiasis mansoni Schistosomiasis Clonorchis sinensis Clonorchis sinensis hepatica Fasciola buski Fasciolopsis viverrini Opisthorchis wastermani Paragonimus TREMATODES (FLUKES) TREMATODES 104 Dexamethasone 0.1 mg/kg/per day 0.1 mg/kg/per Dexamethasone control to may be needed oedema. cerebral -induced therapy Comments / Reference Comments Treat the clothing with 1% malathion Treat powder. 0.5% permethrin or powder ( not available) in 78%. Extra success Permethrin: benefit. Resistance of no combing recommended increasing. Sanford has only 1% lotion. PPUKM permethrin line or be used if first 5%. But can line failed. second Alternative Gamma Benzene Gamma Benzene 1% lotion ( Lindane ®) Suggested Regimen Suggested in seams of clothing. Discard clothing. in seams of clothing. Discard po once 8- 12 hrs, (A-lice ®), (A-lice No drugs. Organism lives in and deposits eggs No drugs. Organism lives then shampoo. q12h po x 8-30d Primary Albendazole 400mg 400mg Albendazole Apply to dry hair for dry hair for Apply to Malathion lotion 0.5% 2 doses 7-9 days apart. #Praziquantel 25 mg/kg 25 mg/kg #Praziquantel Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic Pediculus capitis capitis Pediculus (head lice) pubis Phthirus (pubic lice) ECTOPARASITES corporis Pediculus (body lice) Cerebral cysticercosis Hymenolepiasis 105 Comments / Reference Comments - with Crotami be treated Pruritus may potency 10% or moderate cream ton Reapply fingernails. Trim steroid topical Pruritus handwashing. after hands to gone. mites after 2 wks for persist may 10% cream, Crotamiton Less effective: x then reapply rinse off, apply x 24 hr, all Wash the whole family Treat 24 hrs. cloth and linen in hot water Alternative Gamma benzene 1% wash 1% wash Gamma benzene repeat May hrs. 24 off after once or twice. Suggested Regimen Suggested Primary Permethrin lotion 5% Permethrin skin ®). Apply entire (A-Scabs including chin down from on 8-14 hrs. Leave toes. > persists if itching Repeat or treatment after 2-4 wks or vesicles papules new > 2 children for Safe occur. old. Infant: months 10% or cream Crotamiton daily for sulphur in calamine 3-5days Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Anatomic Site / Diagnosis Site Anatomic (scabies) (scabies) scabiei Sarcoptes patients Immunocompetent 106 infection. infection. (fungal ball) – (fungal Aspergillos Comments / Reference Comments With abscesses, inflammatory With abscesses, is surgery mass or fistulae, required. Voriconazole has shown to be to has shown Voriconazole - than Amphoteri highly effective cin B in Aspergilloma NOT of chemotherapy efficacy Suggest surgery. Suggest proven. if catheter catheter removing Consider infection. related refractory in therapy combination failure. in treatment cases OR OR OR OR 4 divided Ceftriaxone Alternative Doxycycline Doxycycline then Amoxycillin doses IV x 4-6 wk, doses IV x 4-6 Ampicillin 50 mg/kg/dAmpicillin 50 in 500 mg q8h po x 6 mth. 500 mg q8h po x 6 mth. Amphotericin B 0.8-1 mg/kg/d IV, to total total to B 0.8-1 mg/kg/dAmphotericin IV, dose of 2 g x 2-3 wk 5mg/kg/d (ABLC) Ampho B Lipid Complex IV B 1 mg/kg/d* Lipid Amphotericin 3-4 mg/kg/d to gradually increase based and tolerance response on clinical 1 then 50 mg Caspofungin 70 mg on Day thereafter Suggested Regimen Suggested OR OR q12h IV Primary on Day 1, on Day 500mg q6h po. 500mg q6h po. then 4mg/kg q12h IV * Voriconazole 6mg/kg * Voriconazole q6h x 6 wks then Pen V Pen then q6h x 6 wks 200 mg q12h po (>40kg) 200 mg q12h po (>40kg) 100 mg q12h po (<40kg) Total duration : 6-12mths duration Total Benzylpenicillin (Pen G) 4MU (Pen Benzylpenicillin CHAPTER 3e: TREATMENT OF FUNGAL, ACTINOMYCOTIC AND NOCARDIAL INFECTIONS AND NOCARDIAL OF FUNGAL, ACTINOMYCOTIC 3e: TREATMENT CHAPTER Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections /3bViral/3cMycobacterial/3dParasite/3eFungal HIV 3a Chapter Aspergillosis (invasive Aspergillosis A. fumigatus A. flavus A. israelii A. naeslundil, A. viscosus Actinomyocosis Anatomic Site / Diagnosis Site Anatomic 107 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

Suggested Regimens Anatomic Site / Diagnosis Comments Primary Alternative Candidiasis C.lusitaniae & C. guilliermonti If fail to response or deteriorat- C. albicans Fluconazole 800mg (12mg/kg) are resistant to Ampho B, C. C. tropicalis loading dose, then 400mg od ing : Suggest higher Amphotericin B cruzei & C. tropicalis resistant to C. parapsilosis IV/PO Fluconazole OR 0.8 – 1 mg/kg q24h IV NON-INVASIVE (CLINICALLY STABLE WITH Amphotericin B 0.7 mg/kg q24h OR Fluconazole 800 mg q24h IV/po Remove & replace venous OR WITHOUT CENTRAL CATHETER) IV for 2 weeks until last negative catheters INVASIVE CANDIDA/CANDIDAEMIA blood cultures OR Caspofungin 70 mg loading dose followed by 50 mg q24h IV Duration of treatment 14 d after Or last negative blood culture and Anidulafungin 200mg IV loading resolution of sign & symptoms of dose, then 100mg IV infection. Or Voriconazole 400mg (6mg/kg) Echinocandins has been shown bd for 2 doses, then 200mg bd to be superior to Amphotericin B, especially in immunocompromised patients.

C. glabrata may require Fluconazole 800 mg or IV Amphotericin

108 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

Suggested Regimens Anatomic Site / Diagnosis Comments Primary Alternative Non neutropenic patient Caspofungin 70 mg loading dose For endocarditis, Ampho B followed by 50 mg q24h IV 0.6 mg – 1 mg/kg/day, and Fluconazole 800mg (12mg/kg) continue 6 – 8 weeks after loading dose, then 400mg od surgery OR Amphotericin B 0.7mg/kg IV daily Neutropenic Amphotericin B 0.8 – 1 mg/kg/d IV Or Caspofungin 70 mg loading dose Fluconazole 800mg (12mg/kg) followed by 50 mg q24h IV loading dose, then 400mg od Or Or Anidulafungin 200mg IV loading Voriconazole 400mg (6mg/kg) bd for dose ,then 100mg IV od 2 doses, then 200mg bd (3mg/kg) LOCALISED CANDIDIASIS Chronic mucocutaneus Fluconazole 100mg po If unsuccessful, use Ketoconazole 400mg q24H Otitis externa po x 2 wks Surgery may be required Cutaneoues (including paronychia) Clotrimazole Ear Drop q 6-8h x 2 wk * Nystatin Ear Drop q6-8h x 2 wk * unavailable

109 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

Suggested Regimens Anatomic Site / Diagnosis Comments Primary Alternative Apply Nystatin 100,000u/g Apply Clotrimazole cream 1% q8h x If unsuccessful, use ointment q8h x 2 wk 2 wks Itraconazole 200mg q24h po x 2 wk

Oropharyngeal Candidiasis Nystatin suspension 400,000- Fluconazole 100 mg q24h po In patients with extensive 600,000 Units q6h oropharyngeal candidiasis should start with ﬂuconazole IV Use Ampho B in suspected oesophageal candidiasis Fluconazole 200 mg IV/po q24h Amphotericin B 0.3 – 0.7 mg/kg/d then 100mg/d po x 14-21 d IV resistant to triazole drugs.

110 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

Suggested Regimens Anatomic Site / Diagnosis Comments Primary Alternative Meningitis (HIV) Amphotericin B 0.7 – 1 mg/kg/d IV Fluconazole (800 mg per day orally; To stop Fluconazole once + 1200 mg per day CD4>200. 5-Flucytosine 25 mg/kg q6h IV x 2 is favored) plus flucytosine (100 wk then start Fluconazole 400 mg mg/kg per day orally) for 6 Repeat LP after 2 weeks of q24h po x 10 wk then mainte- weeks . Amphotericin B nance : 200 mg q24h OR Fluconazole (1200–2000 mg per day orally) for 10–12 weeks Onychomycosis (Tinea unguium) Fingernail : Toenail: Most nail Terbinafine 250 mg q24h x 6 wk Terbinafine 250mg po 24 h x 12 infection/ hair (79% effective) wks (76% effective) infection/ OR OR widespread Ringworm ( Tinea capitis) Itraconazole po 200 mg q12h x 1 Itraconazole 200mg bd x 1 infection must Athelete’s Foot (Tinea corporis) wk (Pulse dosing - 1 wk each week/month x 3-4 months ( 63% use oral agent. Jock itch (Tinea cruris) month for 3 – 4 mth) effective) Selenium sulphide 2.5% lotion, Ketoconazole 200mg q24h po x 7d Add topical ketocon leave on for 10 mins then wash OR azole or selenium sulfate q24h x 7d Itraconazole 200 mg q24h x 7d shampoo to reduce OR OR transmissibility Tinea versicolor (Malassezia furfur) Clotrimazole cream 1% Fluconazole 400 mg single dose po

111 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

Suggested Regimens Anatomic Site / Diagnosis Comments Primary Alternative OR Miconazole cream 2% OR Ketoconazole cream 2% q24h x 7d Ketoconazole (400mg po single Fluconazole 400mg po single dose Keto (po) 1 stat dose was 97% dose) OR or Itraconazole 400mg po q24h x effective in 1 study. Selenium 200mg q24h x 7 days ) or cream 1 3-7 days sulfide ( Selsun) 2.5% lotion, x q24h x 2wks applied as lather, leave on 10 min then wash off, 1/day or 3-5x/wk. Use for 2-4 wks

112 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

Suggested Regimens Anatomic Site / Diagnosis Comments Primary Alternative Histoplasmosis H. capsulatum Moderate disease: In AIDS, continue lifelong Itraconazole 200 mg solution q12h po x 9 mth suppresion with Itraconazole IMMUNOCOMPETENT Severe disease: 200mg q12h Amphotericin B 0.7 – 1 mg/kg/d IV x (2 g total dose) for 2 weeks then itraconazole 200 mg q12 po x 12 weeks, then 200 mg q24h for 9 months. IMMUNOCOMPROMISED (AIDS) Severe disseminated : Acute phase : Amphotericin B 0.7 mg/kg/d IV OR Lipid Amphotericin B 5mg/kg/d IV for 2 weeks or until clinical improvement Continuation phase (12 wk) : Itraconazole 200 mg q12h po for 12 months Less severe disseminated : Itraconazole 200 mg q8h po x 3d then 100 mg q12h po x 12 wk Meningitis : Amphotericin B 0.7 mg/kg/d IV OR Lipid Amphotericin B 4 mg/kg/d IV x 12 wk Or Flucanazole 800mg od for 12 weeks

113 Chapter 3a HIV /3bViral/3cMycobacterial/3dParasite/3eFungal Infections

Suggested Regimens Anatomic Site / Diagnosis Comments Primary Alternative

Nocardiosis, N. asteroids TMP/SMX : 5 – 10 mg/kg/D OF TMP + 25-50 mg/kg/d of SMX IV/PO CUTANEOUS & LYMPHOCUTANEOUS divided in 2 – 4 doses x 4 – 6 mth TMP/SMX : Initially 15 mg/kg/d of Imipenem 500 mg q6h IV Switch from alternative (for PULMONARY DISSEMINATED BRAIN TMP + 75 mg/kg/d of SMX IV/po + acutely ill patients ONLY) to ABSCESS in 2 – 4 divided doses x 3 – 4 wk Amikacin 7.5 mg/kg q12h IV x 3 – 4 primary as soon as possible. then 10 mg/kg/d of TMP in 2 – 4 wk then oral regimen Maintain with TMP/SMX 800 doses. + TMP-SMX mg x 6 – 12 mth. Duration : 3 mth (immunocompetent) or 6 mth (immunocompromised) Penicilliosis Ampho B 0.5 – 1.0mg/kg/d x 2wks Itraconazole 200mg q8h po x 3d 3rd most common OI in AIDS P. marneffei then then 200 mg q12h po x 12 wks then in S.E. Asia Itraconazole 200mg q24h x 10 wks 200 mg po followed by 200mg/d po for AIDS indefinitely Sporotrichosis Itraconazole or Ampho B 200 mg Depends on clinical site affected S.schenckeii q24h po x 6 mths

114 CHAPTER 4: OPPORTUNISTIC INFECTIONS IN IMMUNOCOMPROMISED

Infecting Organism Preferred Regimen (S) Alternative Regimen (S)

FUNGAL INFECTION Pneumocystis jiroveci (Pneumocystis carinii) Trimethoprim 15 mg/kg/d Trimethoprim 15 mg/kg/d po + + Acute infection Sulfamethoxazole 75 mg/kg/d po or IV x 21 Dapsone 100 mg q24h po x 21 days days in 3-4 div. OR Pentamidine 4 mg/kg/d IV x 21 days (usually Patients with severe PO2 < 70mmHg should reserved for severe cases) receive steroids 15-30 min before TMP/SMX: OR Dose: Prednisolone 40 mg bd X 5/7, then 40 Clindamycin 600 mg IV q8h or 300 – 450 mg po mg od X 5/7 , then 20 mg od X 11/7 q6h + primaquine 30 mg base po/day x 21 day Prophylaxis OR Or Hydrocortisone 100 mg q8h IV (if unable to Atovaquone 750mg bd Dapsone 200mg po + Initiation and discontinuation tolerate orally) Pyrimethamine 75mg po + Folinic Acid 25mg po/per week or Aerosolized Pentamidine 300 mg every mth via TMP/SMX (1 Double Strength/day, 2 Single Respigard II nebulizer 2 agonist (Salbutamol, 2 Strength/day) po puﬀs) or TMP/SMX, 1 Double Strength 3x/wk or TMP/SMX X 1 Single Strength od Or Atovaquone 1500mg od

115 CHAPTER 4: OPPORTUNISTIC INFECTIONS IN IMMUNOCOMPROMISED

Infecting Organism Preferred Regimen (S) Alternative Regimen (S)

Aspergillosis *Voriconazole 6 mg/kg q12h D1, then 4 mg/kg Ampho B Lipid complex 5mg/kg/d iv q12h or 200 mg q12h for > 40kg or 100 mg OR Invasive pulmonary infection q12h for < 40 kg Ampho B 0.7 – 1.4 mg/kg/day OR Itraconazole 200 mg q8h po x 3d, then 400 mg/d Or Salvage Therapy : Caspofungin 70mg/day then 50mg/day Or Posaconazole 200mg qid ,then 400mg/day after disease stable Surgery for localized disease Candida Nystatin 500,000 unit gargle 4-5X /day Fluconazole 100-200 mg q24h po 7-14 days Oropharyngeal (Thrush) OR Itraconazole 200 mg/day (caps) or 100 mg/day oral suspension

Vaginitis Intravaginal miconazole pessaries 500 mg stat Fluconazole 150 mg po stat or 200 mg x 3d or cream (2%) x 7d

116 CHAPTER 4: OPPORTUNISTIC INFECTIONS IN IMMUNOCOMPROMISED

Infecting Organism Preferred Regimen (S) Alternative Regimen (S)

Esophagitis Fluconazole 200-400 mg/d po x 2-3 wks Itraconazole 200 mg/day po (caps) or 100 mg/day oral solution Cryptococcal meningitis Ampho B 0.7 – 1.0 mg/kg/day IV Flucytosine Fluconazole 400 – 800 mg/d Flucytosine 100 100 mg/kg/d x 10 – 14 days po then Flucon- mg/kg/d po x 6 – 10 wks Initial treatment azole 400 mg/day x 8 – 10 wks

Fluconazole 200 mg/d po till CD4> 200 Maintenance therapy cells/ul for 2 readings 3-6 months apart Cryptococcosis without meningitis Fluconazole 200 – 400 mg/d po until immune Itraconazole 200 mg q12h po or 100 mg oral reconstitution achieved suspension/day until immune reconstitution Pulmonary, disseminated or anti – achieved genemia Severe: Ampho B 0.7 – 1.0 mg/kg/day IV for Histoplasmosis Itraconazole 400 mg q24h IV for 2 weeks ,then 14 days. Or Ampho B Lipid Complex Disseminated initial treatment Itraconazole 200 mg q12h or Fluconazole 800 5mg/kg/IV d Then Itraconazole 200mg bd for mg/day for 12 weeks 12 months Mild to moderate: Itraconazole 200 mg q8h po x 3d, then 200 mg q12h po for 12 months or 100 mg oral suspension q12h x 12 wks.

117 CHAPTER 4: OPPORTUNISTIC INFECTIONS IN IMMUNOCOMPROMISED

Infecting Organism Preferred Regimen (S) Alternative Regimen (S)

Maintenance Itraconazole 200 mg q24h until CD4 > 200 cells/ul Penicillium marneﬀei (Penicilliosis) Ampho B 0.7 – 1.0 mg/kg/d for 2 weeks , then Itraconazole 200 mg q8h po x 3d, then 200 mg Initial treatment Itraconazole 400 mg po/d for 10 weeks q12h x 12weeks,then 200mg od

Itraconazole 200 mg po/day until CD4 > Maintenance 200cells/ul for 6 months apart

PARASITIC INFECTIONS Pyrimethamine 100-200 mg loading dose Pyrimethamine + folinic acid (see preferred Toxoplasma gondii encephalitis (Fansidar 4 tab stat), then 50 –100 mg/day po regimen) + Clindamycin 600 mg q6h IV/po for at + sulfadiazine (Fansidar 1 tab bd ) + folinic least 6 wks. Acute infection acid 10-25 mg/day po for at least 6 wks Pyrimethamine and folinic acid (see preferred regimen) plus one of the following: Azithromy- cin 1200-1500 mg/day, Atovaquone 750mg qid , Clarithromycin 1 g po q12h. Azithromycin 900 mg q12h po x 1st day, then 1200 mg/day x 6 wks, then 600 mg/day (patients < 50 kg receive half dose) (salvage therapy). Pyrimethamine 25- 50mg q24h po + folinic acid Pyrimethamine 25-50 mg/d po + folinic acid Suppressive therapy 10-25mg q24h + Sulfadiazine 0.5-1 g q6h po or 10-25 mg q24h + clindamycin 300-450 mg Fansidar 1 tab biweekly q6-8h po.

118 CHAPTER 4: OPPORTUNISTIC INFECTIONS IN IMMUNOCOMPROMISED

Infecting Organism Preferred Regimen (S) Alternative Regimen (S)

Pyrimethamine 25-75 mg/d po + folinic acid 10-25mg q24h, dapsone 100 mg/d po or Azithromycin 600 mg/d po. Discontinue when on HAART if CD4 > 200/mm3 for 2 readings 3-6 months apart

Prophylaxis TMP/SMX 1 DS po qd Dapsone 50 mg/d + pyrimethamine 50 mg/wk + folinic acid 25 mg/wk or Atovaquone 750mg bd Cryptosporidia Treat underlying disease with HAART; treat diarrhoea symptomatically

Isospora TMP/SMX q12h po (2 DS q12h po or 1 DS qid ) X Pyrimethamine 75 mg/day po + folinic acid 10 Acute Infection 10 days, then 1 bd for 3 weeks mg/day x 2 weeks

Suppressive treatment TMP/SMX 1-2 Double Strength 3x/wk po Pyrimethamine 25 mg + folinic acid 5 mg/day.

Microsporidiosis Albendazole 400 mg q12h po x 3 weeks Metronidazole 400 mg q8h po x 1-2 weeks

119 CHAPTER 5A: ANTIBIOTIC PROPHYLAXIS & IMMUNIZATION : Surgical Prophylaxis

CHAPTER 5A: ANTIBIOTIC PROPHYLAXIS & IMMUNIZATION Surgical Antibiotic Prophylaxis Type of Surgery Prophylaxis CommentsComments HEAD & NECK SURGERY Cefuroxime 1.5g IV + Metronidazole 500mg IV Antimicrobial prophylaxis in head & neck OR surgery appears eﬃcacious only for procedures AM/CL 1.2g IV stat at induction/ within 1 hour involving oral/pharyngeal mucosa (eg laryngeal prior to surgery or pharyngeal tumor) but even with prophylaxis, wound infection rate can be high. Uncontaminated head & surgery does not require prophylaxis.

OBSTETRIC / GYNAECOLOGY SURGERY Caesarean section AM/CL 1.2g IV or Ceftriaxone 1 g Upon cord clamping

Hysterectomy (vaginal or abdominal) AM/CL 1.2g IV or Ceftriaxone 1 g For prolonged procedures, give antibiotic q8h

ABDOMINAL SURGERY & PROCEDURES Clean surgery not indicated for antibiotic prophylaxis unless with implant ERCP AM/CL 1.2g IV stat OR Gastroduodenal/ Biliary Clean contaminated and beyond should consider prophylactic antibiotic

120 CHAPTER 5A: ANTIBIOTIC PROPHYLAXIS & IMMUNIZATION : Surgical Prophylaxis

Type of Surgery Prophylaxis Comments

Cefuroxime 1.5 g IV + Metronidazole 500 mg Consider empirical therapy if consider cross Colorectal / Appendicectomy IV stat contamination procedure or peritonitis

Herniaplasty/implant OR Consider additional dose if prolonged Cefoperazone 1 g IV + Metronidazole 500 mg surgery IV stat

INTERVENTIONAL RADIOLOGY PROCEDURES 3rd generation cephalosporin CARDIOVASCULAR & THORACIC SURGERY Valve implant or diabetic patients: 48 hours after surgery Cefotaxime 1 g IV + Cloxacillin 1 g IV Add Vancomycin 1 g IV in (where the OR rate of post-op MRSA is high), give 2 IV Ceftriaxone 1.2g stat + Cloxacillin for 48 more doses q8h for cardiac surgery hours post op (cardiac by pass) Add vancomycin if patient is penicillin allergy Empyema IV Ceftriaxone 1.2g stat ORTHOPAEDIC SURGERY 48 hours after surgery Spine surgery Consider additional dose of antibiotic if Arthroplasty/ Replacement prolonged surgery (more than 6-8 hours) Open reduction of closed fracture with Ceftriaxone 2 g IV at induction Sanford guideline suggested Cefazolin 1-2g internal ﬁxation IV stat as an alternative for non- implant related procedures at induction

121 CHAPTER 5A: ANTIBIOTIC PROPHYLAXIS & IMMUNIZATION : Surgical Prophylaxis

Type of Surgery Prophylaxis Comments Open fracture awaiting surgery Gentamicin and vanco or teico to be given Co-amoxiclav or cephalosporin to combine during induction(once). with genta ( genta only stat dose) Vanco or Teico not to be continued after surgery UROLOGIC SURGERY/ PROCEDURES Amox/Clav 1.2 g IV OR Non-obstructed Ciproﬂoxacin 400mg IV

Obstructed As above but extended up to 5 days

NEUROSURGICAL PROCEDURES Ceftriaxone 2 g IV Cefotaxime for neonates Craniotomy (simple) shunt surgery Add Metronidazole 500mg IV Add Vancomycin 1 g IV in units with high Craniotomy (cross sinuses or naso/ Apuzzo Operative Neurosurgery incidence of MRSA oropharynx) IV Ceftriaxone 2g OD x duration of EVD EVD Neurosurgery. 68(4):996-1005, April 2011

Post Renal Transplant Prophylaxis

1.General 1. TMP/SMX 1 tab ON po x 6 months Consider longer prophylaxis if patient had

122 CHAPTER 5A: ANTIBIOTIC PROPHYLAXIS & IMMUNIZATION : Surgical Prophylaxis

Type of Surgery Prophylaxis Comments 2. Acyclovir 200 mg q8h po (adjust according induction treatment or had treatment for to GFR) x 6 months acute rejection 3. Nystatin syrup 500,000ü q6h x 6 months Consider longer prophylaxis if patient had 2. CMV prophylaxis for high risk patients Valganciclovir 900mg q24h po start within 10 induction treatment or had treatment for days post transplant and for 100 days. acute rejection

123 Chapter 5 B: Bacterial Endocarditis Prophylaxis

CHAPTER 5B : ANTIBIOTIC PROPHYLAXIS & IMMUNIZATION ANTIMICROBIAL PROPHYLAXIS FOR THE PREVENTION OF BACTERIAL ENDOCARDITIS IN PATIENTS WITH UNDERLYING CARDIAC CONDITIONS

The latest guidelines/updated guidelines from both the European Society of Cardiology and American Heart Association advocated the following:

1. Infective endocarditis prophylaxis for dental procedures is reasonable only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis.

2. Apart from indication 1 above, there is limited role of antibiotic prophylaxis against IE in patients undergoing other invasive procedures. However, consideration of antibiotic prophylaxis in high risk groups (as listed in table 1) may be considered in patients undergoing cardiac valve prosthesis surgery, invasive respiratory, gastrointestinal or genitourinary procedures

3. Due to high morbidity and mortality associated with infection, it is reasonable to consider antibiotic prophylaxis in patients undergoing implantation of cardiac pacemakers and deﬁbrillators. (Staph. Aereus being the commonest and most serious pathogen)

4. There is no conclusive data to support widespread use of antibiotic prophylaxis against endocarditis as was previously thought.

5. Widespread use of antibiotic use may be associated with a small but signiﬁcant risk of anaphylaxis, increased incidence of antimicrobial resistant microorganisms, and unnecessary inconvenience and cost to patients.

124 Chapter 5 B: Bacterial Endocarditis Prophylaxis

Patients with the highest risk of bacterial endocarditis Negligible-risk (no greater than general population): o MVP w/o murmur or regurge or myxomatous leaﬂets o Patients with prosthetic cardiac valve o Physiologic murmurs o Patients with history of infective endocarditis o Isolated secondum ASD o Patients with Congenital heart disease (CHD) [Except for the o Surgically repaired ASD/VSD/PDA conditions listed below, antibiotic prophylaxis is no longer o Previous CABG recommended for any other form of CHD] o H/O rheumatic fever or Kawasaki’s Disease without - Unrepaired cyanotic CHD, including palliative shunts and valvular dysfunction conduits - Completely repaired congenital heart defect with Conditions for which prophylaxis is no longer recommended (1997 prosthetic material or device, whether placed by surgery or by moderate risk conditions) catheter intervention, during the ﬁrst 6 months after the procedure - Repaired CHD with residual defects at the site or o Mitral Valve Prolapse with regurgitation adjacent to the site of a prosthetic patch or prosthetic device o Hypertrophic Cardiomyopathy (which inhibit endothelialization) o Rheumatic heart disease and other types of acquired valvular heart disease (eg SLE) o Cardiac transplantation recipients who develop cardiac o Ventricular septal defect valvulopathy (recommended in AHA guidelines, but not in o Atrial septal defect ESC guidelines)-ESC did not mention this in the recommenda tion

125 Chapter 5 B: Bacterial Endocarditis Prophylaxis

PROCEDURES IN WHICH PROPHYLAXIS IS RECOMMENDED (IN HIGH RISK PATIENTS ONLY)

PROCEDURES RECOMMENDED PROPHYLAXIS PROCEDURES NOT RECOMMENDED PROPHYLAXIS Tonsillectomy or adenoidectomy Tympanostomy tube insertion Surgical operations involving intestinal and respiratory mucosa (infected) Flexible bronchoscopy + biopsy Cystoscopy or urethral dilation Endotracheal intubation Urethral catheterization or urinary tract surgery if UTI present Endoscopy + biopsy, Colonoscopy Prostate surgery Elective Caesarean section, D+C, IUD insertion/removal or therapeutic abortion I&D infected tissue PTCA, Cardiac catheterization, TOE Emergency Caesarean

Emergency Caesarean

126 Chapter 5 B: Bacterial Endocarditis Prophylaxis

Dental Procedures for Which Endocarditis Prophylaxis Is Recommended

Antibiotic prophylaxis should be considered in all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa,

Antibiotic prophylaxis is not recommended in the following:

o routine anesthetic injectons through noninfected tissue o taking dental radiographs o placement of removable prosthodontic or orthodontic appliances o adjustment of orthodontic appliances o placement of orthodontic brackets o shedding of deciduous teeth, and bleeding from trauma to the lips or oral mucosa.

127 Chapter 5 B: Bacterial Endocarditis Prophylaxis

Regimens for a Dental Procedure

Situation Agent Regimen: Single Dose 30 to 60 min Before Procedure Adults Children Oral Amoxicillin 2 g 50 mg/kg Ampicillin OR Unable to take oral Cephazolin OR medication 2 g IM/ IV 50 mg/kg IM/ IV Ceftriaxone Cephalexin*# OR 2 g 50 mg/kg Allergic to penicillin Clindamycin OR 600 mg 20 mg/kg or ampicillin (ORAL) Azithromycin OR 500 mg 15 mg/kg Clarithromycin 500 mg 15 mg/kg Allergic to penicillin/ Cephazolin OR 1 g IM/IV 50 mg/kg IM/ IV ampicillin & unable Ceftriaxone# OR 600 mg IM/IV 20 mg/kg IM/ IV to take oral medication Clindamycin phosphate Or other ﬁrst- or second-generation oral cephalosporin in equivalent adult or pediatric dosage. # Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema, or urticaria with penicillins or ampicillin

128 Chapter 5 B: Bacterial Endocarditis Prophylaxis

Agent/ Disease/ Situation Agent Regimen Condition

Adults 2g PROPHYLAXIS AGAINST BACTERIAL Standard general prophylaxis Amoxicillin children 50mg/kg orally 1 hr before ENDOCARDITIS procedure (when appropriate indications arise Adults 2g IM/IV as discussed above) Unable to take oral Ampicillin Children 50mg/kg IM/IV within 30 min. medications before procedure Prophylactic regimens for dental, oral, respira Cephalexin 2g po tory tract, or esophageal OR procedures Allergic to penicillin Azithromycin 500mg po OR Prophylactic regimens Clindamycin 600mg po for genitourinary/ gastrointestinal (Excluding esophageal) Adults: Ampicillin 2g IM/IV + Gentami- procedures High-risk patients Ampicillin + cin 1.5mg/kg (not to exceed 120mg) Gentamicin within 30 min. of starting the procedure; 6 hr later, Ampicillin 1g IM/IV or Amoxicillin 1g po. Children: Ampicillin 50mg/kg IM/IV (not exceed 2.0gm) + Gentamicin 1.5mg/kg within 30 min. of starting the procedure; 6 hrs later, Ampicillin 25mg/kg po.

129 Chapter 5 B: Bacterial Endocarditis Prophylaxis

Agent/ Disease/ Situation Agent Regimen Condition

High-risk patients allergic Vancomycin + Adults: Vancomycin 1g IV over 1-2 hrs + to Ampicillin/ Amoxicillin Gentamicin Gentamicin 1.5mg/kg IV/IM (not exceed 120mg) complete injection/infusion within 30 min. of starting procedure. Children: Vancomycin 1g IV over 1-2 hrs + Gentamicin 1.5mg/kg IV/IM (not exceed 120mg) complete injection/infusion within 30 min. of starting the procedure

Moderate-risk patients Amoxicillin or Adults: Amoxicillin 2g orally 1 hr before Ampicillin procedure, or Ampicillin 2g IM/IV within 30 min. of starting the procedure Children: Amoxicillin 50mg/kg po 1 hr before procedure, or Ampicillin 50mg/kg IM/IV within 30 min. of starting the procedure.

130 Chapter 5 B: Bacterial Endocarditis Prophylaxis

AGENT/ DISEASE/ SITUATION AGENT CONDITION REGIMEN

Moderate-risk patients Vancomycin Adults: Vancomycin 1g IV over 1-2 hrs; allergic to Ampicillin complete infusion within 30 min. of / Amoxicillin starting the procedure Children: Vancomycin 20mg/kg IV over 1-2 hrs; complete infusion within 30 min. of starting the procedure

131 Chapter 5C : Medical Prophylaxis & Post Exposure Prophylaxis

CHAPTER 5C : MEDICAL PROPHYLAXIS & POST EXPOSURE PROPHYLAXIS

Agent/ Disease/ Condition Situation Agent Regimen

URINARY TRACT INFECTION (reﬂux Trimethoprim 1-2mg/kg q24h po nocte grade 3-4) OR (recurrent infection, vesico uteric Nitrofurantoin 1-2mg/kg q24h po nocte reﬂux, pyelonephritis in pregnancy) OR Cephalexin 125-250mg q24h po NEONATAL GP B STREPTOCOCCAL Ampicillin 2g loading dose then 1g IV q4h until Commence during labour till delivery Rx DISEASE delivery of infected mother reduced risk of Treat during labour if previously delivered OR neonatal GBS. infant with invasive GBS. GBS bacteriuria Pen G (Benzylpenicillin) 5mu IV Pregnancy : eradicate carriage with oral or screening swabs positive OR if (loading dose) followed by 2.5 MU q4h until delivery bacampicillin 400mg q12h x 1 wk -preterm <37 weeks -PROM > 18 hours Consider Erythromycin 500mg q4h until -intrapartum temp >38 delivery in penicillin-allergic patients

CHICKEN POX (NEONATAL) Acyclovir 20mg/kg q8h x 7 d Babies born to mothers who develop OR chicken pox 5 days before or 3 days after Varicella Zoster Immunoglobulin* delivery.

132 Chapter 5C : Medical Prophylaxis & Post Exposure Prophylaxis

Agent/ Disease/ Condition Situation Agent Regimen

PPM & DEFIBRILLATOR PROPHYLAXIS During induction, ﬂucloxacillin 1gm stat IV followed by PO Recommended by NICE 2008 and ﬂucloxacillin 1gm at 8h, 16h and 24h Circulation 1998

POST-SPLENECTOMY/SICKLE-CELL Antibiotic Prophylaxis: Vaccine: DISEASE 1) Pneumococcal vaccine 0.5mL SC Antimicrobial prophylaxis < 5 y.o : or IM Penicillin V 125-250mg q12h po for life OR Amoxycillin 2 weeks before surgery. 7-14 days 20mg/kg/day or 500mg PO q12h (adult) >5 y.o : Pen V 250mg after emergency splenectomy or prior q12h PO for at least 2 year in children post splenectomy or up to to discharge. 16 y.o Lifelong not recommended. Indefinitely for patients with Booster every 5 years an underlying immunocompromised state and asplenia. 2) Meningococcal Vaccines polysac- Penicillin allergy – EES 400mg PO q 12 h or Azithromycin 250mg charide ( quadrivalent) 0.5mL SC. PO q 24h Schedule as above. Booster every 5 years 3) Haemophilus Influenzae Type B (HIB) 0.5mL IM thigh/upper arm ( In patients with bleeding disorders, this can be given SC) Schedule as above No booster required 4) Influenza 0.5mL deep SC ANNUALLY RHEUMATIC FEVER (secondary Penicillin V 250mg q12h po OR Erythromycin 250mg q12h po OR With carditis: life-long treatment prophylaxis) Benzathine 250mg/kg IM every 3-4 weeks Without carditis: continue for 5yrs

133 Chapter 5C : Medical Prophylaxis & Post Exposure Prophylaxis

Agent/ Disease/ Condition Situation Agent Regimen

SEXUAL ASSAULT / CONTACTS Ceftriaxone 125mg IM single dose Repeat HIV serology in 12 wks + Metronidazole 2g single dose + Doxycycline 100mg q12h x 7d OR Azithromycin 1g po single dose

MALARIA Non-immune individuals Chloroquine Chloroquine phosphate 500 mg (300 entering malaria endemic Should start 2 wks before entry, mg base) po once /wk areas, sensitive to continue while in and for 4 wks Paediatric dose: Chloroquine 5 chloroquine. after leaving the area mg/kg base/wk, up to 300 mg base

Chloroquine-resistant Meﬂoquine 5mg/kg PO 250 mg po once /wk areas once a week Paediatric dose: (refer to CDC yellow (begin 1 week before travel <15 kg: 5 mg/kg book) until 4 weeks 15-19 kg: ¼ tablet post travel) 20-30 kg: ½ tablet 31-45 kg: ¾ tablet >45 kg: 1 tablet

Doxycycline Commence few days 100 mg po q24h before departure, continue while Paediatric dose: 2 mg/kg/d up to in and for 4 wks after leaving the 100 mg/d area.

134 Chapter 5C : Medical Prophylaxis & Post Exposure Prophylaxis

Agent/ Disease/ Condition Situation Agent Regimen Alternative: Primaquine contraindicated in Primaquine pregnancy 30 mg base daily Paediatric dose: 0.5 mg/kg base daily Chloroquine phosphate 500 mg Chloroquine phosphate (300 mg base)po once /wk + Paediatric dose: Chloroquine5 Proguanil mg/kg base/wk, up to 300 mg base Proguanil 200 mg once/d Peadiatric dose : < 2 yrs : 50 mg once /d 2-6 yrs : 100 mg once /d 7-10 yrs : 150 mg once /d >10 yrs : 200 mg once /d

PNEUMOCYSTIS CARINII PNEUMONIA Prophylaxis is indicated if the TMP/SMX 480mg po Pentamidine 300mg in 6ml water by CD4 count is <200 x 106/L or q24h aerosol after the 1st attack. (1 SS tab od) OR OR Dapsone 100mg OD TMP/SMX 480-960mg po q24h (1 DS tab od) OR TMP/SMX 960mg po 3x/wk

135 Chapter 5C : Medical Prophylaxis & Post Exposure Prophylaxis

Agent/ Disease/ Condition Situation Agent Regimen

TOXOPLASMOSIS Following an acute therapy, a Pyrimethamine Pyrimethamine 25-75mg po q24h + prophylactic regimen should be Folinic acid folinic acid 10 mg/d + sulfadiazine continued for the duration of Sulfadiazine 0.5-1g po q6h functional immunosuppression.

136 Post Exposure Prophylaxis

Post-Exposure Prophylaxis Some infectious diseases can be prevented by post-exposure prophylaxis (PEP). For maximum eﬀectiveness, administered within 24 hours of exposure. PEP usually for persons with close face-to-face/intimate contact with infected individual. Casual contact usually does not warrant PEP. (essentials)

Agent/ Disease/ Condition Situation Agent Regimen

MENINGITIS Any quinolone (PO) x 1 dose Avoid tetracycline in children < 8 yrs. (N. MENINGITIDIS) OR (essentials) Rifampin 600mg (PO) q 12 h x 2 days

MENINGITIS Children: Household: If there is one (HAEMOPHILUS INFLUENZAE) Rifampicin 20mg/kg po (not to exceed 600mg) q24h x 3doses unvaccinated contact <4 yrs in the Adult: Rifampicin 600mg q24h x 3day household, Rifampicin is recommended for all household Must be administered within 24 hours of close face-to-face contacts except pregnant women. exposure to be eﬀective. Otherwise observe and treat if infection develops. Childcare Facilities: With 1 case, if attended by unvaccinated children < 2 yrs: no prophylaxis. If > 2 cases in 60 days & unvaccinated children attend, prophylaxis recommended for children & personnel.

137 Post Exposure Prophylaxis

Agent/ Disease/ Condition Agent Regimen

VIRAL INFLUENZA Oseltamivir (Tamiflu) 75mg (PO) q 24 h for duration of Give to non immunized contacts and Influenza virus type A or B outbreak or at least 7 days after close contact to an infected high risk contacts even if immunized. person. Begin at onset of outbreak or within 2 days of close contact to infected person. For CrCl 10-30mL/min, give 75mg (PO) 48 h Oseltamivir is active agst both Influenza A & B. Rimantadine and Amantadine only active agst Infl A

Administer ASAP after exposure. DIPHTERIA Erythromycin 500mg PO q6h x 1 week OR Eﬀectiveness is greatly reduced Benzathine penicillin 1.2mu (IM) x 1 dose after 24 hours.

TB INH 300mg (PO) q 24 h x 9 months (5mg/kg/24 h for 6 months) For INH, monitor SGOT, SGPT M. TUBERCULOSIS NAG weekly x 4, then monthly. Mild OR elevations are common and resolve Rifampin 600mg (PO) q 24 h x 4 months spontaneously. INH should be stopped if SGOT/SGPT levels > 5 x normal. Gonorrhea Ceftriaxone 125mg (IM) x 1 dose Administer ASAP after sexual OR exposure. Ceftriaxone also treats Any oral quinolone x 1 dose incubating syphilis.

138 Post Exposure Prophylaxis

Agent/ Disease/ Condition Agent Regimen

Syphilis Benzathine penicillin 2.4 MU (IM) x 1 dose Obtain HIV serology OR Doxycycline 100mg PO q 12 h x 1 week Varicella ( Chicken pox) For exposure < 72 hours, give VZIG- Varicella Zoster Immuno- Administer ASAP after exposure ( < 72 globulin 625mcg (IM) and 1 dose to immunocompromised hosts hours) Varicella vaccine is a live and pregnant women ( esp with respi conditions) 1.25ml (1 vial attenuated vaccine and should not be or 125 iu) for each 10kg. Maximum dosage of 6 ml. For other given to immunocompromised or exposure > 72 hours, consider Acyclovir pregnant patients. If varicella develops, start acyclovir treatment VZIG prophylaxis is recommended for individuals who fulﬁll all of the following three criteria: Alternative: Varicella vaccine 0.5mL (SC) x 1 dose. Repeat in 4 1. A clinical condition which increases weeks the risk of severe varicella: includes immunosuppressed patients, neonates where maternal varicella develops 5 days before and 2 days after delivery, and pregnant women. 2. No antibodies to varicella-zoster virus. Signiﬁcant exposure to chickenpox or herpes zoster

139 Post Exposure Prophylaxis

Agent/ Disease/ Condition Agent Regimen

Hepatitis B Unvaccinated: Hep B Immune globulin ( HBIG) 0.06mL/kg (IM) Previously vaccinated Known x 1 dose + responder ( anti HBsAg antibody HBV vaccine (40mcg HBsAg/mL) deep deltoid (IM) at 0, 1, 6 levels > 10IU/mL) : no treatment months ( can use 10mcg dose in healthy adults < 40 years) Known non responder ( anti-HBsAg antibody levels < 10IU/mL) Treat as if Hepatitis B speciﬁc immunoglobulin (HBIG) Newborn: 200iu unvaccinated Antibody status within 24h of birth 1M unknown: Obtain HBsAg antibody levels. If testing not possible and Adults and children > 10 years: 500iu IM results unavailable in 24 hours of exposure, give HBIG + 1 dose of HBV Vaccine ( booster)

1. All babies born to HbsAg positive mothers and who had acute hepatitis B during pregnancy. 2. Health workers who have been successfully immunized should be given a booster dose of vaccine unless they are known to have adequate protective level of antibody

140 Post Exposure Prophylaxis

Agent/ Disease/ Condition Agent Regimen

Hepatitis A HAV Vaccine 1mL (IM) x 1 dose

Rabies (virus) Pre-Exposure Prophylaxis Post-Exposure Prophylaxis (WHO, CPG- adult vaccina- Intramuscular Inj : Three 1.0 mL Human Diploid tion) Cell Vaccine (HDCV) on days 0, 7, 28. 1. Wound toilet by scrubbing with soap and water for 5 mins 2. (a) Previously unimmunized individual: 1 ml HDCV (vaccine) by IM followed by 5 further doses at days 3,7,14, 30, 90 plus RIG 20 iu/kg. Treatment may be stopped if the animal is found conclusively to be free of rabies. (b) Previously fully immunized individuals: - 2 doses of HDCV 1.0 ml 1M on days 0 and 3-7. RIG treatment not needed. For adults the vaccine is given in the deltoid area, right and left arm; for children, it may be given in the anterolateral aspect of the thigh. An immunized person is anyone who has received a complete series of vaccine, or a person who has received a pre-exposure or post-exposure series of any rabies vaccine who has an adequate rabies antibody level

141 Post Exposure Prophylaxis

Agent/ Disease/ Condition Agent Regimen

Measles Human Normal Immunocompromised children and adults Immunoglobulin HNIG, 1M < 1 yr 250mg 1-2 yrs 500mg 3 yrs 750mg Tetanus Human Tetanus Speciﬁc Tetanus Prone Wound** Immunoglobulin (TIG) i) In previously immunized patient + booster 250 iu or 500 iu if more than 24h have lapsed >10 years previously: since injury a booster dose of tetanus vaccine (Paeds: 150u/kg IM near to sites of exposure or ii) In unimmunized or immunization injury). status not known with certainty: a full 3 dose course of tetanus vaccine plus a dose of TIG in a diﬀerent site.

142 Post Exposure Prophylaxis

AGENT/ DISEASE/ CONDITION AGENT REGIMEN

Dirt Tetanus Dirt Tetanus Clean , Non Tetanus Clean , Non Prone Wound Prone Wound Prone Wound Tetanus Prone Wound Criteria Age of wound : > 6 hours Age of wound : < 6 hours Conﬁguration: Stellate,avulsion Conﬁguration: Linear Depth: > 1 cm Depth: < 1 cm Mechanism of injury : Mechanism of injury : Sharp surface, Missile,crush,burn,frostbite glass, injury Devitalised tissue: Present Devitalised tissue: Absent Contamina- Contamination (dirt,saliva) : Present tion (dirt,saliva) : Absent

Td 1,2 TIG Td TIG Unknown or < 3 Yes Yes Yes No doses 3 or more doses No 3 No No 4 No

1= Td= Tetanus & Diptheria toxoids adsorbed (adult), TIG=Tetanus immune globulin 2= yes if wound > 24 hours old 3= Yes if > 5 years since last booster 4= yes if > 10 years since last booster

143 Post Exposure Prophylaxis

Baseline testing of all exposed Health Care Workerss should be performed for ALL exposures. HBV PEP should be initiated immediately (within 24 hours) according to the following table from CDC MMWR 2001 Vol 50 No. RR-11, Table 3:

Recommended Post Exposure Prophylaxis for exposure to hepatitis B virus

Vaccination and antibody Treatment response status of exposed workers* Source HBsAg† positive Source HBsAg† negative Source unknown or not available for testing HBIG§ x 1 and initiate HB Unvaccinated Initiate HB vaccine series Initiate HB vaccine series vaccine series Previously vaccinated Known responder** No treatment No treatment No treatment HBIG x 1 and initiate Known nonresponder†† No treatment If known high risk source, treat as if revaccination or HBIG x 2 source were HBsAg positive §§ Test exposed person for Antibody response unknown No treatment Test exposed person for anti-HBs anti-HBs 1. If adequate, no treatment is 1. If adequate,** no necessary treatment is necessary 2. If inadequate, administer vaccine 2. If inadequate,†† booster and recheck titer in 1–2 administer HBIG x 1 months and vaccine booster

144 Post Exposure Prophylaxis

* Those previously infected with H are immune to re-infection and do not require PEP. † Hepatitis B surface antigen § Hepatitis B immune globulin; dose is 0.06 mL/kg intramuscularly. When indicated, HBIG should be administered as soon as possible (preferably within 24 hours). Its eﬀectiveness >7 days after exposure is unknown. ** A responder has adequate levels of serum antibody to HBsAg (anti-HBs ≥ 10 mlU/mL). †† A nonresponder has inadequate response to vaccination (anti-HBs < 10 mlU/mL). §§ The option of giving one dose of HBIG and reinitiating the vaccine series is preferred for nonresponders who have not completed a second 3-dose vaccine series. For persons who previously completed a second vaccine series but failed to respond, two doses of HBIG one month apart are preferred.

145 Chapter 6 Travel Vaccines and Vaccines in PPUKM

CHAPTER 6a : TRAVEL VACCINES

Infection/Possible Organisms Prophylaxis Regimens Comments

Meningococcal meningitis

N. meningitidis (Menveo) Meningococcal conjugate vaccine 0.5mL (IM) Acquired via close face to face contact ( airborne aerosol/ droplet exposure) *FREE Only for staﬀ going for haj and umrah. > 1 month prior to travel to outbreak area Protective against > meningitides serotypes To be supplied through the Infection Control Unit. A, C, Y, and W, but misses B serotype.

Typhoid Fever

S. typhi Typhoid vaccine 0.5mL (IM). Booster every 2 Contraindicated in immunocompromised years for repeat travellers hosts and children < 6 years old. Availability : Typhoid vaccine 20 doses /vial.

Yellow fever

Yellow fever virus Yellow fever vaccine 0.5mL (SC). Booster every 10 years for repeat travellers Availability : If government servant going for oﬃcial visit, can obtain free vaccination from IMR Virology Unit ( 03-26162671) http://www.imr.gov.my/org/viro.htm#3

146 Chapter 6 Travel Vaccines and Vaccines in PPUKM

If going for a holiday, patient to pay and get vaccination + certiﬁcate from one of these: -Twin Tower Medical City (03-23822000) -Kita Clinic, Dayabumi Complex (03-26989740) -Klinik Berkat, Ampang Point (03-42515450

Inﬂuenza Annual vaccine. For healthy persons > Inactivated viral inﬂuenza vaccine Single 0.5mL dose (IM) 50 years, health care personnel, adults (Vaxigrip/Fluarix) with high risk conditions, ( heart disease, lung disease, diabetes, renal dysfunction, hemoglobinopathies, immunosuppression)

147 Vaccines in PPUKM

CHAPTER 6 b : VACCINES IN PPUKM

Manuf Indication Vaccine Preparation Availability Notes act’R Dosage and Administration Hepatitis B Engerix-B GSK Adult: Adult 20 yo: 20 mcg IM The 20 mcg vaccine may (Adsorbed puriﬁed 20 g/1 ml deltoid region at 0,1,6 mth. be given to subjects 11 surface antigen Paed: Paed 19 yo: 10 mcg IM yo and 15 yo at 0,6 mth. protein of hepatitis B 10 g /0.5 ml deltoid region or IM Should not be virus – thiomersal anterolateral thigh in administered in the preservative-free) neonates, infants and young buttock, intradermally children at 0,1,6 mth. or intravascularly.

Euvax B LG Life 10 mcg/0.5ml Kedai Adult & children 15 yo: A Booster dose is not (Hepatitis B Sciences Farmasi/ dose of 20 mcg. required. recombinant Ward supply Neonates & children 15 yo: vaccine) (Formulary) A dose of 10 mcg. Infection for staﬀ *Adult Schedule: vaccine FOC 1st dose: at elected date for staﬀ only 2nd dose: 1 month after 1st dose 3rd dose: 6 months after 1st dose

148 Vaccines in PPUKM

CHAPTER 6 b : VACCINES IN PPUKM

Manuf Indication Vaccine Preparation Availability Notes act’R Dosage and Administration

Invasive Hiberix GSK 1 dose/0.5 ml Kedai farmasi/ Primary vaccination: Vaccine is for IM inj. Haemophi- [Haemophilus influenza Ward supply 3 doses in the 1st 6 mths of But, may be given as SC lus influenzae type b (Hib) vaccine] (Formulary) life and may be started from in pt with thrombocy- type b (Hib) 6 wks of age. topenia or bleeding disease Booster dose: disorder. 2nd yr of life (recommended). Hiberix may be mixed Previously unvaccinated in the same syringe infant 6-12 mth: 2 inj at 1 with GSK vaccines mth-interval, followed by a Infanrix, or Tritanrix HB. booster in the 2nd yr of life. Other injectable Previously unvaccinated vaccines should always child 1-5 yo: 1 dose. be given at different inj sites. For SC use only. Chicken pox Varilrix GSK 1 dose/0.5 ml Kedai farmasi Children >12 mth and <12 Should not be mixed with (Live attenuated Oka (NF) yo: 1 dose. Adult and strain of varicella- children >13 yo: 2 doses other vaccines in the same zoster virus) with an interval of 6-10 syringe. wks. After reconstitution, in should be administered immediately.

149 Vaccines in PPUKM

Manuf Indication Vaccine Preparation Availability Notes act’R Dosage and Administration Measles, Priorix [Live GSK 1 dose/0.5 ml Kedai farmasi/ Children 12-15 mth: For SC/IM use. mumps and attenuated Schwarz Ward supply 0.5 ml. rubella measles, RIT 4385 (Formulary) Booster dose: (MMR) mumps (derived At 4-6 yo. from Jeryl Lynn strain) and Wistar RA 27/3 rubella strains of viruses] Tetanus TT Vaccine Bio Inj 0.5ml Ward Tetanus prevention ( >7 yo): Maintain immunization of Farma IM: 0.5 ml followed after 4-8 (Adsorbed tetanus supply nd woman against Tetanus vaccine) (Formulary) wks by a 2 dose and after a through childbearing rd further 6-12 mths by a 3 period: dose. Two 0.5 mL injections given Booster dose: 2 months apart from 6 th IM: 0.5 ml every 10 yrs months of pregnancy (recommended). onwards, 3rd dose 1 year later. Thereafter 1 dose of 0.5mL injection for every subsequent pregnancy & followed by a booster every 10 years.

150 Vaccines in PPUKM

Manuf Indication Vaccine Preparation Availability Dosage and Administration Notes act’R

Rubella Live Rubella Vaccine GSK Inj 1dose/1ml Ward supply A single dose of 0.5 ml is Stored in the dark at 2-8 C *FOC for staff (Formulary) to be administered by for < 8 hrs if not used deep SC inj into the upper immediately. arm. Do not give <1 mth before/after administration of other live virus vaccines Meningo- Menveo ACWY Novar- 1 dose/0.5 ml Kedai farmasi > 11 yr: 0.5 ml IM. Must not be administered coccal (Group A, C, W & Y tis *only FOC for intravascularly, subcutane- meningitis conjugated meningo- staff going for ously or intradermally. coccal vaccine) Haji. (Infection Control Unit) Primary vaccination: For deep IM inj. Infanrix DTP + Infanrix-IPV GSK Ward Supply st 1 dose/0.5 ml 3 doses in the 1 yr of life and can only be mixed in the Polio (Combined diptheria- (Formulary) may be started from 2 mths (Prefilled same syringe as Hiberix ® tetanus-accellular of age. Should have an syringe interval of at least 1 month - haemophilus Influenzae. pertussis, and between subsequent doses. Infants: the preferred site inactivated polio) Booster dose: 2nd yr of life, after the primary of inj is the anterolateral course is completed aspect of the thigh. Older children: vaccine should be administered in

151 Vaccines in PPUKM

Manuf Indication Vaccine Preparation Availability Dosage and Administration Notes act’R before 6 mths of age. An the deltoid. interval of at least 6 mths It is preferable that each after completion of primary subsequent dose is given at vaccination should be alternate sites. respected. Also as booster dose for children up to 18 yrs, who have previously been immunized with DTP and polio antigens. HPV (Cervical Gardasil Merck 1 dose/0.5 Kedai farmasi Administered IM in the Must not be injected cancer, genital [Quadrivalent ml (NF) deltoid region of the upper intravascularly. warts) Human Papillomavi- arm or in the higher SC and intradermal rus (Types 6, 11, 16, anterolateral area of the administration are not 18) Recombinant thigh as 3 separate 0.5-ml recommended. Vaccine] doses according to the Indicated for prophylaxis of following schedule: Cervical cancer and genital 1st dose: at elected date warts 2nd dose: 2 mths after the 1st dose 3rd dose: 6 mths after the

152 Vaccines in PPUKM

CHAPTER 6 b : VACCINES IN PPUKM

Manuf Indication Vaccine Preparation Availability Notes act’R Dosage and Administration 1st dose If an alternate vaccination schedule is necessary, the 2nd dose should be administered at least 1 mth after the 1st dose, and the 3rd dose should be administered at least 3 mths after the 2nd dose

Cervarix [Quadrivalent GSK 1 dose/0.5mL Kedai farmasi Three 0.5mL doses IM in the Must not be injected Human Papillomavirus (NF) deltoid region at 0, 1, 6 mth intravascularly or (Types 16, 18) schedule. intradermally. Recombinant Vaccine] Indicated for prophylaxis of Cervical cancer only

153 Vaccines in PPUKM

Manuf Indication Vaccine Preparation Availability Dosage and Administration Notes act’R >2 years old Pneumo Aventis 1 dose/0.5 Kedai farmasi / Primary immunization Do not inject IV. 23 (Purified Strep ml Ward supply (> 2yo): A single inj of 0.5 ml It should be given at least Pneumoniae (Formulary) given IM or SC deltoid 2 wks before scheduled polysaccharides of *FOC for staff region. splenectomy, cochlear 23 types) Booster dose: Must not be implant surgery and before Pneumo- given within 5 yr except high chemotherapy / immuno- coccal risk subjects or under suppressive therapy. infection(pneu immunosuppressive monia, treatment. meningitis, < 2 years old Synflorix GSK 1 dose/0.5mL Infants 6 weeks - 6 months: Should be given IM acute otitis Kedai farmasi (Pneumococcal 3 doses of 0.5mL with an injection media, ) (NF) polysaccharide & interval of at least 1 month The preferred sites are adsorbed nontypeable between doses. A booster anterolateral aspect of the Haemophilus dose is recommended at thigh in children <12 influenza protein D least 6 months after the last months or the deltoid conjugate vaccine, 10 priming dose muscle of the upper arm in valent adsorbed) Infants 7-11 months: 2 children >12 months doses of 0.5mL with interval Must not be injected of at least 1 month between intravascularly or doses. A 3rd dose is intradermally recommended in the 2nd

154 Vaccines in PPUKM

Manuf Indication Vaccine Preparation Availability Dosage and Administration Notes act’R

year of life with an interval of at least 2 months. Children 12-23 months: 2 doses of 0.5 mL with an interval of at least 2 months between doses. 2 months-5 years Pﬁzer 1 dose/0.5mL Farmasi Infants 2-6 months: Give IM Prevenar 13 tingkat 7 (NF) 3 doses with interval of at Contains the same 7 (Pneumococcal least 1 month between serotypes contained in 13-valent conjugate doses. 1st dose may be as Prevenar, using the same vaccine) early as 6 weeks of age. 4th carrier protein CRM197. (booster) dose Children who have recommended between begun immunization 12-15 months OR 1st dose with Prevenar may from the age of 2 months, complete immunization 2nd dose 2 months later. 3rd by switching to Prevenar (booster) dose is 13 at any point in the recommended between schedule 11-15 months.. Unvacci- Children 15 months - 5 nated Children > 7 months: years who have received 4 doses of Prevenar may

155 Vaccines in PPUKM

Manuf Indication Vaccine Preparation Availability Dosage and Administration Notes act’R Infants 7-11 months: receive 1 dose of 2 doses with interval of at Prevenar 13 (at least 8 least 1 month between doses. 3rd dose is weeks after the 4th dose recommended in the 2nd of Prevenar) to elicit year of life immune responses to Children 12-23 months: 2 doses with interval of at the 6 additional least 2 months between serotypes. doses Children 2-5 years: 1 single dose of 0.5 mL

Inﬂuenza Vaxigrip Aventis 1 dose/0.5mL Kedai farmasi Adults >18 yo: Do not inject IV. prophylaxis (Inactivated split virion (Formulary) IM deltoid region: single 0.5 inﬂuenza vaccine/ mL inj. thiomersal free) Tuberculosis Bacillus Calmette- Japan Inj live, Ward supply Adult: Give via Intradermal inj Guerin (BCG) Vaccine BCG Lab freeze-dried 10 (Formulary) Intradermal: 0.1 ml with a 25 or 26 gauge doses/ml Infant < 12 mth: needle at the deltoid Intradermal: 0.05 ml region of the upper arm, * 1 amp = 0.5 mg which will minimize post vaccination lymphade

156 Vaccines in PPUKM

Manuf Indication Vaccine Preparation Availability Dosage and Administration Notes act’R nopathy. Do not exclude air. Skin test for hypersensitivity to tuberculoprotein prior to BCG immunization. Keep in the dark (sensitive to light). Keep opened ampoules at 2-8 C for max 6 hrs.

Gastro- Rotarix GSK 1 dose/0.5mL Kedai farmasi 2 doses, with an interval of For oral use only. Do not enteritis (Live attenuated human (NF) at least 4 weeks between inject. There are no rotavirus vaccine) doses. First dose from 6 restrictions on the infant’s weeks of age, second dose consumption of food or by age of 24 weeks. liquid.

157 APPENDIX 1 Step Wise Guide in Post Exposure Prophylaxis Step Wise Guide in Post Exposure Prophylaxis

Step 1: Determine the Exposure Code (EC)

Is the source material bloody ﬂuid, or other potentially infectious material (OPIM) + or an instruments contaminated with one of these subtances?

YES NO No PEP Needed

OPIM Blood or Bloody Fluid

What type of expose has occured?

Mucous membrane of Intact skin Percutaneous skin,integrity only ** exposure compromised

Volume No PEP Needed Severity

Small Large Less Severe More Severe (e.g., large-bore hollow needle, (e.g. few (e.g., several drops, (e.g.,solid needle superﬁal major blood splash scratch) deep puncture, visible blood drops, short and/or longer duration on device, or needle used in duration (i.e,. several minutes or more) source patient’s artery or vein)++

EC 1 EC 2 EC 2 EC 3

Step 2: Determine the HIV Status Code (HIV SC)

Suggested Regime What is the HIV status of the exposure source? LOW RISK No treatment (EC1, SC1) / Monotherapy HIV Negative HIV Positive Status Unknown Source Unknown MEDIUM RISK 2 NRTI (EC1, SC2) (Basic Regime) (EC2, SC1) Zidovudine 300mg bd + Lamivudine 150mg bd No PEP Needed

HIGH RISK 2 NRTI + PI (EC2, SC2) (Expanded Regime) Lower titer exposure Higher titer exposure (EC3, SC 1/2) As Above + Kaletra (e.g., asymptomatic (e.g., advanced AIDS, primary HIV 2 tab bd and high CD4 count***) infection, high or increasing viral load or low CD4 count***)

? SOURCE/STATUS Monotherapy / (risk high) 2 NRTI HIV SC 1 HIV SC 2 HIV SC Unkown

158 APPENDIX 2 TDM APPENDIX 2 Therapeutic Drug Monitoring Sampling Guideline

159 APPENDIX 2 TDM

160 A Brucellosis 4, 69 Abdominal surgery 120 Burkholderia pseudomallei 66, 70 Abscess (Brain) 5 Burn wound sepsis 62 Abscess (Perirectal) 28 Abscess (Hepatic) 26 Acanthamoeba keratitis 99 C Acinetobacter 49, 70 Candida albicans 76 Actinomyces Israeli 70, 107 Candida glabrata 76 Actinomyces naeslundil 107 Candida krusei 76 Actinomyces viscosus 107 Candida parapsilosis 76 Actinomycosis 107 Candida tropicalis 76 Aeromonas hydrophila 70 Candida Diphtheriae 71 Amoebic meningoencephalitis 99 Caesarean (prophylaxis) 120 Ancylostoma braziliense 101 Calymmatobacterium Anthrax 70 Granulomatis 52 Appendicectomy (prophylaxis) Campylobacter jejuni 22, 70 121 Candida 76, 116 Arthropasty (prophylaxis) 121 Candida albicans 108 Ascaris lumbricoides 100 Candida parapsilosis 108 Aspergillosis 107, 116 Candida tropicalis 108 Aspergillus 76 Candida, non-albicans 76 Aspiration pneumonia( see Candidiasis – invasive 108 pneumonia) 46 Candidiasis –localised 109 Athelete’s Foot 111 Cardiovascular & thoracic surgery Avian (H5N1) inﬂuenza 90 prophylaxis 121 Cardiovascular Infections 1 Catheter-Related Infection 36 B Cavernous Sinus Thrombosis 65 Babesia 99 Cellulitis, Orbital 17 Bacilus anthracis 70 Cellulitis/ Erysipelas 62 Bacterial Endocarditis Cerebral cysticercosis 105 Prophylaxis 124 Cervarix vaccine 152 Bacterial vaginosis 72 Cervical cancer vaccine 152 Bacteroides fragilis 70 Cervicitis 50 Bacteroids 5 Cestodes 104 Balantidium coli 96 Chancroid 51, 72 Bartonella 4, 70 Chicken Pox (neonatal) prophylaxis BCG vaccine 156 132 Bell’s palsy 89 Chicken pox 89 Biliary (prophylaxis) 120 Chicken pox vaccine 149 Biliary Sepsis 22 Chlamydia pneumonia 71 Bite 59 Chlamydia trachomatis 12, 52, 71 Blastocystis 96 Chlamydia trachomatis 71 Body lice 105 Cholangitis 22 Boils/ carbuncles 62 Cholecystitis 22 Bone & joint infections 53 Chorioamnionitis 35 Bordetella pertussis 70 Chryseobacterium meningosepticum Borrelia burgdorferi 69, 70 71 Brain abscess 5 Citrobacter 71 Brain abscess, pulmonary disseminated Clostridium 71 114 Clostridium diﬃcile toxin 23 Bronchitis 44 CMV 85 161 CMV prophylaxis 123 Encephalitis 5 CNS Infection 5 Endocarditis 1 Colorectal ( prophylaxis) 121 Endomyometritis 35 Combivir (Azt + 3TC) 81 Endophthalmitis 14, 16 Community acquired pneumonia Engerix B vaccine 148 44 Entamoeba histolytica 97 Conjunctivitis 12 Enterobacter 71 CONS ( Coagulase Negative Enterococcus 71 Staphylococci) 20, 54, 74 Enterobacteriaceae 5 Contact lens bacterial keratitis 13 Enterobius vermicularis 101 Coxiella 71 Epididymitis/ Epididymoorchitis Craniotomy (prophylaxis) 122 31 Cryptococcal meningitis 117 Epiglotitis 43, 72 Cryptococcosis without meningitis ERCP (prophylaxis) 120 Cryptococcus 76 ESBL 72 Cryptosporidia 119 Escherichia coli 72 Cryptosporidium parvum 97 Euvax B vaccine 148 Cutaneous larva migrans 101 EVD (External Ventricular Drainage) Cyclospora 96 (prophylaxis) 122 Cyst passers 98 Extrapulmonary TB 92 Cystitis 29, 34 CytoMegaloVirus (CMV) 85 F Filiariasis 102 D Francisella tularensis 72 Decubitis ulcers 62 Fungal Infections 107 Dermatophytes 76 Fusarium 76 Diabetic foot infection 56 Diarrhea 97 Didanosine (ddi/Videx) 81 G Dientamoebiasis 97 Gaednerella vaginalis 72 Diphteria 43 Gallbladder 22 Diphtheria prophylaxis 138 Gardasil vaccine 152 Diphtheriae 71 Gas gangrene 58 Diverticulitis 26 Gastric ulcer 24 Dracunculiasis 101 Gastroduodenal (prophylaxis) 120 DTP + Polio vaccine 151 Gastroenteritis 22, 157 Duodenal (Gastric Ulcer) 24 Gastrointestinal Infections 22 Dysenteric 97 Genital warts 50 Genitourinary Tract & Gynaecological E Infections 29 E coli 72 Giardia lamblia 98 Echinococcus granulosus 104 Gonococcal infection 50 Ectoparasites 105 Gonococcal ophthalmia neonatorum EENT Infections (Eye, Ear, Nose, 12 Throat) 12 Gonococcal urethritis 30 Efavirenz (Stocrin)81 Gonococcus 73 Elephantiasis 102 Gonorrhea 50 Elizabethkingia 71 Gonorrhea prophylaxis 138 Empyema (prophylaxis) 121

162 Granuloma inguinale 52 Infective endocarditis 1 Influenza prophylaxis 156 H Influenza vaccine 147, 156 HACEK group 4 Influenza virus A&B 90 Haemophilus ducreyi 51 Interventional radiology Haemophilus influenza 6 procedures (prophylaxis) 121 Haemophilus Influenza Meningitis Intestinal tapeworms 104 prophylaxis 137 Isospora 119 Haemophilus influenza vaccine 149 Isospora belli 98 Haemophilus Infuenzae 72 Haemorrhagic viral fever 88 Hantavirus 88 J Head & neck surgery 120 Jock itch 111 Head lice 105 Health-care associated 48 Health-care associated pneumonia K (see pneumonia)48 Kaletra (Lopinavir 133mg + Helicobacter pylori 24, 72 Ritonavir 33mg ) 82 Hemophilus ducreyi 72 Keratitis 12 Hepatic abscess 26, 97 Klebsiella Pneumoniae (ESBL) 49, Hepatitis A prophylaxis 141 72 Hepatitis B 26 Hep B Post Exposure Prophylaxis 144 L Hepatitis B prophylaxis 140 Lamivudine (3TC/Epivir) 81 Hepatitis B vaccine 148 Larva migrans 102 Hepatitis C 27, 88 Laryngitis 43 Herniaplasty (prophylaxis) 121 Legionella species 72 Herpes simplex 5, 51,87, 89 Leishmania donovani 99 Herpes zoster 63 Leptospira interrogans 73 Hiberix vaccine 149 Leptospirosis 5, 69 Histoplasma 77 Line infection36, 65 Histoplasmosis 113, 117 Lower respiratory tract infection HIV INFECTIONS 81 44 Hookworm infection 101 Lyme disease 69 Hospital acquired pneumonia 46 Lymphogranuloma venereum 52 HPV vaccine 152 HSV 87 Human herpes virus 89 M Human papillomavirus 50 M. Tuberculosis prophylaxis 138 Hymenolepiasis 105 MAI (Mycobacterium Avium- Hysterectomy (prophylaxis) 120 Intracellulare) 93

Malaria prophylaxis 134 I Mastoiditis 19 Impetigo 63 Measles prophylaxis 142 Implant ( prophylaxis) 121 Measles, mumps and rubella Indinavir (Crixivan) 82 (MMR) vaccine 150 Infanrix-IPV vaccine 151 Medical Prophylaxis 132 Infected wound 63 Meliodosis 66

163 Meningitis 5, 72 Osteomyelitis 53 Meningitis (HIV) 111 Otitis externa 18 Meningitis prophylaxis 137 Otitis media 19 Meningococcal meningitis vaccine 146, 151 Meningococci, 6, 73 P Menveo vaccine 151 Pallidum 51 Microsporidiosis 119 Pancreas 27 Microsporidium 99 Papillomavirus 50, 89 MRSA 49, 74 Paragonimus wastermani 102 MSSA 74 Parasite infections 96, 118 Muscle 58 Pasteurella multocida 73 Mycobacterium bovis 92 Pediculus capitis 105 Mycobacterium chelonae 94 Pediculus corporis 105 Mycobacterium kansasii 94 Pelvic inflammatory disease 32 Mycobacterium leprae 94 Penicilliosis 114, 118 Mycobacterium scrofulaceum 94 Penicillium marneffei 77, 114, 118 Mycobacterium tuberculosis 9, 91 Peptostreptococcus 75 Mycobacterium ulcerans 94 Perirectal abscess 28 Peritonitis 28 Pharyngitis 43 N Phthirus pubis 105 N asteroids 114 Plague 75 Necrotising myofascitis 58 Pneumo 23 vaccine 154 Necrotizing fasciitis 63 Pneumococcal vaccine 154 Neiseirra Meningitidis prophylaxis 137 Pneumocystis carinii 115 Neiserria gonorrhoeae 73 Pneumocystis carinii pneumonia Neisseria meningitis 73 prophylaxis 135 Nematodes Intestinal 100 Pneumocystis jiroveci 115 Nematodes Extraintestinal 100 Pneumonia –hospital acquired 46 Neonatal Gp B Streptococcal Disease Pneumonia 48 prophylaxis 132 Post Exposure Prophylaxis 132 Neurosurgical procedures (prophylaxis) Post Renal Transplant Prophylaxis 122 122 Neurosyphilis, 11 Post- Splenectomy prophylaxis 133 Nevirapine (Viramune) 81 Post trauma with sepsis 63 Nocardia 73 Post-intraarticular Injection 57 Nocardiosis 114 PPM & Defibrillator prophylaxis Non-thyphoid fever 68 133 Prevenar 155 O Priorix vaccine 150 Obstetric / gynaecology surgery 120 Proctitis 50 Odontogenic Infections 40 Prostatitis 50 Oesophageal candidiasis 110, 117 Prosthetic joint 57 Onychomycosis 111 Prosthetic valve 1, 4 Open fracture (prophylaxis) 122 Proteus mirabilis 73 Opportunistic infections 115 Proteus vulgaris 73 Orbital cellulitis 17 Protozoa – intestinal 96 Oropharyngeal candidiasis 110 Protozoa Extraintestinal 99 Orthopaedic surgery (prophylaxis) 121 Providencia 73

164 Pseudomonas Aeruginosa 48, 54, 73 Staph aureus 5, 74 Pseudomonas maltophilia 75 Staphylococcus 74 Psittacosis 4 Stavudine (d4T/Zerit) 81 Pubic lice 105 Stenotrophomonas 49, 75 Pulmonary TB 91 Strep Pneumoniae 75 Pyelonephritis 29, 34 Streptococci 5 Pyomyositis 58 Streptococcus 75 Streptococcus Pneumoniae, 6 Q Streptococcus pyogenes 75 Q fever 4 Strongyloides stercoralis 101 Surgical Antibiotic Prophylaxis 120 R Synﬂorix vaccine 154 Rabies prophylaxis 141 Syphilis 51 Respiratory Tract Infection 43 Syphilis prophylaxis 139 Rheumatic fever prophylaxis 133 Rickettsiae 73 Rickettsial disease 68 T Ringworm 111 T. pallidum 51 Ritonavir (Norvir) 82 TB & AIDS 92 Rochalimaea 70 TB during pregnancy 92 Rotarix vaccine 157 TB meningitis 92 Rotavirus 157 TB Prophylaxis 138 Rubella vaccine 151 Tenofovir –Emtricitabine (Tenvir EM) 81 Tetanus prophylaxis 142 S Tetanus vaccine 150 S. schenkeii 114 Tinea capitis 111 Salmonella typhi 74 Tinea corporis 111 Sarcoptes scabiei 106 Tinea cruris 111 SARS CoV 90 Tinea unguium 111 Scabies 106 Tinea versicolor 111 Scedosporium 77 Tonsilitis 43 Schistosomiasis 104 Toxocariasis 102 Scrub Typhus 68 Toxoplasma gondii encephalitis Septic Arthritis 57 118 Septic Miscarriage 35 Toxoplasmosis 100 Serratia marcesens 74 Tracheobroncitis 43 Sexual assault / contacts Trichinellosis 102 prophylaxis 134 Trichomonas vaginalis 100 Sexually Transmitted Diseases 50 Trichuris trichiura 101 Shigella 24 Tropical bacterial infections 66 Shigella 74 Tuberculosis - Pulmonary 91 Sickle-cell disease prophylaxis 133 Tuberculosis vaccine 156 Sinusitis 43 Tularemia 72 Skin & soft tissue infections 59 Typhoid fever 68 SLN ( d4T/3TC/Nevirapine) 82 Typhoid fever vaccine 146 Spine surgery (prophylaxis) 121 Typhus 68 Splenectomy 28 Sporothrix 77 U Sporotrichosis 114 Upper respiratory tract infection 44

165 Urethritis 50 Urethritis (non gonococcal) 30, 34 Urinary Tract Infection 30 Urinary Tract Infection (Pregnant) 34 Urinary tract infection prophylaxis 132 Urologic surgery / procedures (prophylaxis) 122

V Vaginal Candidiasis 33 Vaginitis 31 Vaginitis, Candida 116 Varicella (chicken pox) 89 Varicella (chicken pox) prophylaxis 139 Varicella Zoster 90 Varicella zoster virus (VZV) 87 Varilrix vaccine 149 Vascular 65 Vaxigrip vaccine 156 Ventilator associated pneumonia 48 Vibrio cholera 24, 75 Viral fever 88 Viral infections 85 Viral inﬂuenza prophylaxis 138 Visceral larva migrans 102 VZV 87

W Warts 89

X Xanthomonas 75

Y Yellow fever vaccine 146 Yersinia enterocolitica 75 Yersinia pestis 75

Z Zidovudine (Azt/Retrovir) 81 Zygomycetes 77

166