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Medical Review(S) Clinical Review
CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 200327 MEDICAL REVIEW(S) CLINICAL REVIEW Application Type NDA Application Number(s) 200327 Priority or Standard Standard Submit Date(s) December 29, 2009 Received Date(s) December 30, 2009 PDUFA Goal Date October 30, 2010 Division / Office Division of Anti-Infective and Ophthalmology Products Office of Antimicrobial Products Reviewer Name(s) Ariel Ramirez Porcalla, MD, MPH Neil Rellosa, MD Review Completion October 29, 2010 Date Established Name Ceftaroline fosamil for injection (Proposed) Trade Name Teflaro Therapeutic Class Cephalosporin; ß-lactams Applicant Cerexa, Inc. Forest Laboratories, Inc. Formulation(s) 400 mg/vial and 600 mg/vial Intravenous Dosing Regimen 600 mg every 12 hours by IV infusion Indication(s) Acute Bacterial Skin and Skin Structure Infection (ABSSSI); Community-acquired Bacterial Pneumonia (CABP) Intended Population(s) Adults ≥ 18 years of age Template Version: March 6, 2009 Reference ID: 2857265 Clinical Review Ariel Ramirez Porcalla, MD, MPH Neil Rellosa, MD NDA 200327: Teflaro (ceftaroline fosamil) Table of Contents 1 RECOMMENDATIONS/RISK BENEFIT ASSESSMENT ......................................... 9 1.1 Recommendation on Regulatory Action ........................................................... 10 1.2 Risk Benefit Assessment.................................................................................. 10 1.3 Recommendations for Postmarketing Risk Evaluation and Mitigation Strategies ........................................................................................................................ -
Empiric Antimicrobial Therapy for Diabetic Foot Infection
Empiric Antimicrobial Therapy for Diabetic Foot Infection (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2019) Infection Severity Preferred Empiric Regimens Alternative Regimens Comments Mild Wound less than 4 weeks duration:d Wound less than 4 weeks duration:e • Outpatient management • Cellulitis less than 2 cm and • cephalexin 500 – 1000 mg PO q6h*,a OR • clindamycin 300 – 450 mg PO q6h (only if recommended ,a • cefadroxil 500 – 1000 mg PO q12h* severe delayed reaction to a beta-lactam) without involvement of deeper • Tailor regimen based on culture tissues and susceptibility results and True immediate allergy to a beta-lactam at MRSA Suspected: • Non-limb threatening patient response risk of cross reactivity with cephalexin or • doxycycline 200 mg PO for 1 dose then • No signs of sepsis cefadroxil: 100 mg PO q12h OR • cefuroxime 500 mg PO q8–12h*,b • sulfamethoxazole+trimethoprim 800+160 mg to 1600+320 mg PO q12h*,f Wound greater than 4 weeks duration:d Wound greater than 4 weeks duratione • amoxicillin+clavulanate 875/125 mg PO and MRSA suspected: q12h*,c OR • doxycycline 200 mg PO for 1 dose then • cefuroxime 500 mg PO q8–12h*,b AND 100 mg PO q12h AND metroNIDAZOLE metroNIDAZOLE 500 mg PO q12h 500 mg PO q12h OR • sulfamethoxazole+trimethoprim 800+160 mg to 1600/320 mg PO q12h*,f AND metroNIDAZOLE 500 mg PO q12h Moderate Wound less than 4 weeks duration:d Wound less than 4 weeks duration:e • Initial management with • Cellulitis greater than 2 cm or • ceFAZolin 2 g IV q8h*,b OR • levoFLOXacin 750 -
Eyelid and Orbital Infections
27 Eyelid and Orbital Infections Ayub Hakim Department of Ophthalmology, Western Galilee - Nahariya Medical Center, Nahariya, Israel 1. Introduction The major infections of the ocular adnexal and orbital tissues are preseptal cellulitis and orbital cellulitis. They occur more frequently in children than in adults. In Schramm's series of 303 cases of orbital cellulitis, 68% of the patients were younger than 9 years old and only 17% were older than 15 years old. Orbital cellulitis is less common, but more serious than preseptal. Both conditions happen more commonly in the winter months when the incidence of paranasal sinus infections is increased. There are specific causes for each of these types of cellulitis, and each may be associated with serious complications, including vision loss, intracranial infection and death. Studies of orbital cellulitis and its complication report mortality in 1- 2% and vision loss in 3-11%. In contrast, mortality and vision loss are extremely rare in preseptal cellulitis. 1.1 Definitions Preseptal and orbital cellulites are the most common causes of acute orbital inflammation. Preseptal cellulitis is an infection of the soft tissue of the eyelids and periocular region that is localized anterior to the orbital septum outside the bony orbit. Orbital cellulitis ( 3.5 per 100,00 ) is an infection of the soft tissues of the orbit that is localized posterior to the orbital septum and involves the fat and muscles contained within the bony orbit. Both types are normally distinguished clinically by anatomic location. 1.2 Pathophysiology The soft tissues of the eyelids, adnexa and orbit are sterile. Infection usually originates from adjacent non-sterile sites but may also expand hematogenously from distant infected sites when septicemia occurs. -
Synergistic Activity of Ampicillin and Cloxacillin
144 THE JOURNAL OF ANTIBIOTICS APR. 1969 SYNERGISTIC ACTIVITY OF AMPICILLIN AND CLOXACILLIN PROTECTIVE EFFECT OF CLOXACILLIN ON ENZYMATIC DEGRADATION OF AMPICILLIN BY PENICILLINASE, AND THERAPEUTIC ACTIVITY OF MIXTURES OF AMPICILLIN AND CLOXACILLIN MlNORUNlSHIDA, YASUHIROMlNE Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan and Shogo Kuwahara Department of Microbiology, Toho University School of Medicine, Tokyo, Japan (Received for publication February 15, 1969) A mixture of ampicillin (aminobenzyl penicillin, AB-PC) and cloxacillin (methylchlorophenylisoxazolyl penicillin, MCI-PC) showed an excellent bacteri- cidal activity even at low concentrations in which either of the penicillins alone did not have any activity against a clinically isolated strain of Escherichia colt, resistant to both of these penicillins. In this case, the microbial degrada- ion of AB-PC, caused by penicillinase (PC-ase), was strongly inhibited in the presence of MCI-PC. The enzymatic hydrolysis of AB-PC by extracellular nd cell-bound PC-ase, obtained from an AB-PC resistant strain of Staphylo- coccus aureus, was also inhibited in the presence of MCI-PC. Against that, t a under comparable conditions, penicillin G (PC-G) was almost completely destroyed by cell-bound PC-ase from this organism. An in vivo synergism was observed when mixtures of AB-PC and MCI-PC were applied for the treatment of mice challenged with a clinically isolated strain of E. coli resistant to both of these penicillins. Similar results were obtained in the treatment of mice experimentally infected with a strain of Staphylococcus aureus, which is highly resistant to AB-PC, but sensitive to MCI-PC. A decrease in the rate of hydrolysis of methicillin (dimethoxyphenyl penicillin, DMP-PC) by staphylococcal penicillinase (PC-ase) was first noted by Rolinson and his co-workers^. -
Cefalexin in the WHO Essential Medicines List for Children Reject
Reviewer No. 1: checklist for application of: Cefalexin In the WHO Essential Medicines List for Children (1) Have all important studies that you are aware of been included? Yes No 9 (2) Is there adequate evidence of efficacy for the proposed use? Yes 9 No (3) Is there evidence of efficacy in diverse settings and/or populations? Yes 9 No (4) Are there adverse effects of concern? Yes 9 No (5) Are there special requirements or training needed for safe/effective use? Yes No 9 (6) Is this product needed to meet the majority health needs of the population? Yes No 9 (7) Is the proposed dosage form registered by a stringent regulatory authority? Yes 9 No (8) What action do you propose for the Committee to take? Reject the application for inclusion of the following presentations of cefalexin: • Tablets/ capsules 250mg • Oral suspensions 125mg/5ml and 125mg/ml (9) Additional comment, if any. In order to identify any additional literature, the following broad and sensitive search was conducted using the PubMed Clinical Query application: (cephalexin OR cefalexin AND - 1 - pediatr*) AND ((clinical[Title/Abstract] AND trial[Title/Abstract]) OR clinical trials[MeSH Terms] OR clinical trial[Publication Type] OR random*[Title/Abstract] OR random allocation[MeSH Terms] OR therapeutic use[MeSH Subheading]) Only one small additional study was identified, which looked at the provision of prophylactic antibiotics in patients presenting to an urban children's hospital with trauma to the distal fingertip, requiring repair.1 In a prospective randomised control trial, 146 patients were enrolled, of which 69 were randomised to the no-antibiotic group, and 66 were randomised to the antibiotic (cefalexin) group. -
Antimicrobial Stewardship Guidance
Antimicrobial Stewardship Guidance Federal Bureau of Prisons Clinical Practice Guidelines March 2013 Clinical guidelines are made available to the public for informational purposes only. The Federal Bureau of Prisons (BOP) does not warrant these guidelines for any other purpose, and assumes no responsibility for any injury or damage resulting from the reliance thereof. Proper medical practice necessitates that all cases are evaluated on an individual basis and that treatment decisions are patient-specific. Consult the BOP Clinical Practice Guidelines Web page to determine the date of the most recent update to this document: http://www.bop.gov/news/medresources.jsp Federal Bureau of Prisons Antimicrobial Stewardship Guidance Clinical Practice Guidelines March 2013 Table of Contents 1. Purpose ............................................................................................................................................. 3 2. Introduction ...................................................................................................................................... 3 3. Antimicrobial Stewardship in the BOP............................................................................................ 4 4. General Guidance for Diagnosis and Identifying Infection ............................................................. 5 Diagnosis of Specific Infections ........................................................................................................ 6 Upper Respiratory Infections (not otherwise specified) .............................................................................. -
Clinical Characteristics and Outcomes of Paediatric Orbital Cellulitis in Hospital Universiti Sains Malaysia: a Five-Year Review
Singapore Med J 2020; 61(6): 312-319 Original Article https://doi.org/10.11622/smedj.2019121 Clinical characteristics and outcomes of paediatric orbital cellulitis in Hospital Universiti Sains Malaysia: a five-year review Ismail Mohd-Ilham1,2, MBBS, MMed, Abd Bari Muhd-Syafi1,2, MBBS, Sonny Teo Khairy-Shamel1,2, MD, MMed, Ismail Shatriah1,2, MD, MMed INTRODUCTION Limited data is available on paediatric orbital cellulitis in Asia. We aimed to describe demographic data, clinical presentation, predisposing factors, identified microorganisms, choice of antibiotics and management in children with orbital cellulitis treated in a tertiary care centre in Malaysia. METHODS A retrospective review was performed on children with orbital cellulitis aged below 18 years who were admitted to Hospital Universiti Sains Malaysia, Kelantan, Malaysia, between January 2013 and December 2017. RESULTS A total of 14 paediatric patients fulfilling the diagnostic criteria for orbital cellulitis were included. Their mean age was 6.5 ± 1.2 years. Boys were more likely to have orbital cellulitis than girls (71.4% vs. 28.6%). Involvement of both eyes was observed in 14.3% of the patients. Sinusitis (28.6%) and upper respiratory tract infection (21.4%) were the most common predisposing causes. Staphylococcus aureus (28.6%) was the leading pathogen. Longer duration of hospitalisation was observed in those infected with methicillin-resistant Staphylococcus aureus and Burkholderia pseudomallei. 10 (71.4%) patients were treated with a combination of two or three antibiotics. In this series, 42.9% had surgical interventions. CONCLUSION Young boys were found to be more commonly affected by orbital cellulitis than young girls. -
Preseptal and Orbital Cellulitis
Journal of Microbiology and Infectious Diseases / 2014; 4 (3): 123-127 JMID doi: 10.5799/ahinjs.02.2014.03.0154 REVIEW ARTICLE Preseptal and orbital cellulitis Emine Akçay, Gamze Dereli Can, Nurullah Çağıl Yıldırım Beyazıt Univ. Medical Faculty Atatürk Training and Research Hospital Dept. of Ophthalmology, Ankara, Turkey ABSTRACT Preseptal cellulitis (PC) is defined as an inflammation of the eyelid and surrounding skin, whereas orbital cellulitis (OC) is an inflammation of the posterior septum of the eyelid affecting the orbit and its contents. Periorbital tissues may become infected as a result of trauma (including insect bites) or primary bacteremia. Orbital cellulitis generally occurs as a complication of sinusitis. The most commonly isolated organisms are Staphylococcus aureus, Streptococcus pneu- moniae, S. epidermidis, Haempphilus influenzae, Moraxella catarrhalis and S. pyogenes. The method for the diagnosis of OS and PS is computed tomography. Using effective antibiotics is a mainstay for the treatment of PC and OC. There is an agreement that surgical drainage should be performed in cases of complete ophthalmoplegia or significant visual impairment or large abscesses formation. This infections are also at a greater risk of acute visual loss, cavernous sinus thrombosis, meningitis, cerebritis, endo- phthalmitis, and brain abscess in children. Early diagnosis and appropriate treatment are crucial to control the infection. Diagnosis, treatment, management and complications of PC and OC are summarized in this manuscript. J Microbiol Infect Dis 2014; 4(3): 123-127 Key words: infection, cellulitis, orbita, preseptal, diagnosis, treatment Preseptal ve Orbital Sellülit ÖZET Preseptal selülit (PS) göz kapağı ve çevresindeki dokunun iltihabi reaksiyonu iken orbital selülit (OS) orbitayı ve onun içeriğini etkileyen septum arkası dokuların iltihabıdır. -
Orbenin-DC® (Benzathine Cloxacillin)
ORBENIN-DC- cloxacillin benzathine suspension Merck Sharp & Dohme Corp. ---------- Orbenin-DC® (benzathine cloxacillin) F-27865909 DRY COW (VACA SECA) Intramammary Infusion (Infusión intramamaria) LONG ACTING FORMULA (FÓRMULA DE LARGA ACCIÓN) CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. DESCRIPTION: Orbenin-DC (benzathine cloxacillin) is a stable, nonirritating suspension of benzathine cloxacillin containing the equivalent of 500 mg of cloxacillin per disposable syringe. Orbenin-DC is manufactured by a nonsterilizing process. Benzathine cloxacillin is a semisynthetic penicillin derived from the penicillin nucleus, 6-amino- penicillanic acid. Benzathine cloxacillin is the benzathine salt of 6-[3-(2-chlorophenyl)-5- methylisoxazolyl-4-carboxamido] penicillanic acid. The low solubility of Orbenin-DC results in an extended period of activity. Therefore, directions for use should be followed explicitly. ACTION: Benzathine cloxacillin is bactericidal in action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell wall mucopeptide. It is active against gram-positive organisms associated with mastitis such as Staphylococcus aureus and Streptococcus agalactiae and, because of its resistance to penicillinase, penicillin G-resistant staphylococci which may be the cause of mastitis. Appropriate laboratory tests should be conducted, including in vitro culturing and susceptibility tests on pretreatment milk samples collected aseptically. SUSCEPTIBILITY TEST: The Kirby-Bauer1 procedure, utilizing antibiotic susceptibility disks, is a quantitative method that may be adapted to determining the sensitivity of bacteria in milk to Orbenin-DC. For testing the effectiveness of Orbenin-DC in milk, follow the Kirby-Bauer procedure using the 1 mcg oxacillin susceptibility disk. -
Management of Penicillin and Beta-Lactam Allergy
Management of Penicillin and Beta-Lactam Allergy (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017) Key Points • Beta-lactams are generally safe; allergic and adverse drug reactions are over diagnosed and over reported • Nonpruritic, nonurticarial rashes occur in up to 10% of patients receiving penicillins. These rashes are usually not allergic and are not a contraindication to the use of a different beta-lactam • The frequently cited risk of 8 to 10% cross-reactivity between penicillins and cephalosporins is an overestimate based on studies from the 1970’s that are now considered flawed • Expect new intolerances (i.e. any allergy or adverse reaction reported in a drug allergy field) to be reported after 0.5 to 4% of all antimicrobial courses depending on the gender and specific antimicrobial. Expect a higher incidence of new intolerances in patients with three or more prior medication intolerances1 • For type-1 immediate hypersensitivity reactions (IgE-mediated), cross-reactivity among penicillins (table 1) is expected due to similar core structure and/or major/minor antigenic determinants, use not recommended without desensitization • For type-1 immediate hypersensitivity reactions, cross-reactivity between penicillins (table 1) and cephalosporins is due to similarities in the side chains; risk of cross-reactivity will only be significant between penicillins and cephalosporins with similar side chains • Only type-1 immediate hypersensitivity to a penicillin manifesting as anaphylaxis, bronchospasm, -
Antibiotic Use for Sepsis in Neonates and Children: 2016 Evidence Update
Antibiotic Use for Sepsis in Neonates and Children: 2016 Evidence Update Aline Fuchsa, Julia Bielickia,b, Shrey Mathurb, Mike Sharlandb, Johannes N. Van Den Ankera,c a Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, Basel, Switzerland b Paediatric Infectious Disease Research Group, Institute for Infection and Immunity, St George's University of London, London, United Kingdom c Division of Clinical Pharmacology, Children’s National Health System, Washington, DC, USA WHO-Reviews 1 TABLE OF CONTENTS 1. INTRODUCTION ............................................................................................................................... 3 1.1. Aims ......................................................................................................................................... 3 1.2. Background ............................................................................................................................. 3 1.2.1. Definition and diagnosis ................................................................................................. 3 Neonatal Sepsis ............................................................................................................................... 3 Paediatric Sepsis ............................................................................................................................. 4 Community versus hospital acquired sepsis .................................................................................. 5 1.2.2. Microbiology .................................................................................................................. -
Peri-Orbital and Orbital Cellulitis
Peri-Orbital and Orbital Cellulitis Reference: 1694 Written by: Judith Gilchrist Peer reviewer: Lucy Hinds Approved: November 2017 Review Due: September 2021 Purpose To guide the management of periorbital and orbital cellulitis Intended Audience Clinical staff managing the patient Author: Judith Gilchrist Review date: September 2021 © SC(NHS)FT 2017. Not for use outside the Trust. Page 1 of 3 CAEC Registration Identifier: 1694 Sheffield Children’s (NHS) Foundation Trust Peri-Orbital and Orbital Cellulitis Table of Contents 1. Introduction 2. Guideline Content A. Pre-septal Cellulitis B. Orbital Cellulitis 3. References 1. Introduction Pre–septal (periorbital) cellulitis is a common condition and the majority of cases can be managed on oral antibiotics and discharged home. Orbital cellulitis is however a serious condition with significant long term morbidity and requires aggressive management. Differentiating between the two conditions is important but fortunately relatively simple. 2. Intended Audience Clinical staff managing the patient 3. Guideline Content A. PRE-SEPTAL CELLULITIS Symptoms include lid swelling and redness. Signs include lid swelling and erythema but otherwise normal eye examination. Take history and perform basic eye examination – remember to check visual acuity, pupils and eye movements. Management If under 3 months old - admit under medics and refer to ophthalmology and ENT. If over 3 months old – If systemically well, sensible parents and mild features may be discharged on PO antibiotics (co-amoxiclav). Author: Judith Gilchrist Review date: September 2021 © SC(NHS)FT 2017. Not for use outside the Trust. Page 2 of 3 CAEC Registration Identifier: 1694 Sheffield Children’s (NHS) Foundation Trust Peri-Orbital and Orbital Cellulitis Mild features include - Lids can be opened, the eye itself is not red, eye movements and visual acuity are normal and none of the symptoms or signs of orbital cellulitis below are present.