Antibiotics Update Dr Kieran Hand ClConsultant Pharmac ist ‐ AiAnti‐IfInfect ives University Hospital Southampton NHS Foundation Trust 38th UK Medicines Information Practice Development Seminar University of Warwick, 13th – 14th September 2012 A game of two halves •First half •Second half –An interesting anecdote – Ask the audience Prize-winning schoolgirls take quantum leap from babies’ bottoms to dairy cows’ udders By Jimmy Woulfe, Mid-West Correspondent Thursday, May 03, 2012 Two Co Limerick schoolggyirls have found a widely-used cream for soothing babies’ bottoms is a great remedy for dairy cows with sore udders caused by mastitis. Both girls did their research on the family farms run by their dads. They foun d tha t a tu b o f Su docrem cos ting €4 can c lear mas titis in a da iry cow just as quickly as widely-used veterinary injections which cost €60 per treatment. Evaluating appropriateness: what factors influence choice / dose / route / duration of therapy? • Presenting complaint / signs & • Previous antibiotics symptoms • Biochemistry / haematology results / • Evidence of infection (+SIRS) urine dipstick • Past medical history (e.g. prosthetic • Allergy / intolerance valve, epilepsy) •Pregnancy / breastfeeding • Immune status/immunosuppressants •Organ dysfunction • Family / social contacts •GI absorption / swallowing • Occupation / hobbies •Expert advice •Travel history •Source control •Pets / animal contact •Local pathogen epidemiology and • DIAGNOSIS and likely pathogens resistance • Severity of infection • Antibiotic spectrum • Prescriber’s training / experience • Site of infection (penetration) • Peer adidvice / consultan t preference • DiDosing regimen (PK/PD) •Local guidelines / policy • Interacting drugs (e.g. iron and • Recent contact with healthcare doxycycline) • Recent or previous microbiology / • Ethnicity (e. g. G6PD deficiency). serology investigations. Skin & soft tissue infections: in vitro sensitivities from Southampton GPs 11/12 100 90 80 Penicillin 70 e Flucloxacillin iv tt 60 Erythromycin 50 Doxycycline sensi 40 %% Rifampicin 30 Fusidic acid 20 Ciprofloxacin 10 0 Staph aureus Southampton GP isolates 2011/12 Take a chance on me •Trust me I’m a doctor •I have a remarkable memory for facts • IIm’m going to start you on ‘Cefanmet’ • My rabbit’ s foot has never failed me Ebbinghaus’ forgetting curve (try to remember it) Which of these two men would you send to the supermarket? There is another way… •Bear with me while I consult our treatment guidelines • Hmm, they don’t seem to cover your particular circumstances •I think I will get some expert advice Hospital pharmacist knowledge of antibiot ics and ifinfect ion Assessment results by subject area (ITT) 100 75 Baseline (all) % 50 Final (all) 25 0 t iology tibiotic ination ectrum ogen atmen f action f -effects actions nitoring inf man inf nn mm rr pp hh ee oo mm Eli Pat Inte Side epide Antibiotic s Antibiotic Choice of a of Choice Empirical tr Principles of Principles of Mechanis m Diagnosis/mo Hand K & Jubraj J 2005 (MSc) What do patients deserve? •Option one: Parachute •Option two: Provide an in a micro/ID doctor IT system for decision‐ (and pharmacist) support 24/7 From maps to Apps 2008 2011 Guiding treatment choice Protecting patients from harm Tailoring treatment to patients •“Existing guidance on the management of some infections may be too long and complex for many doctors to have time to absorb, according to the Healthcare‐Associated Infections (HCAI) Working Group at the RCP. The group have now produced a handy one‐page summary of guidelines to help busy doctors identify what is most important for them in their routine clinical practice.” De‐skilling? This page intentionally blank Audience empowerment •Option A •Option B • Revision of the basics – • Heads‐up on the latest choosing an antibiotic trends in resistance / regimen that may save prescribing and a patient’s life (or advances in science of intervening if a regimen infection management is likely to fail) Four main groups of bacteria 1. Gram positive 2. GtiGram negative 3. Anaerobes 4. Atypical Even Ebbinghaus could remember this! Groups are defined by their response to antibiotics Generally speaking... Gram -ve GI-tract Anaerobes Respiratory Mouth, teeth, Peritonitis throat, sinuses Biliary infection & lower bowel Pancreatitis Abscesses UTI Dental infection PID Peritonitis Pneumonia Appendicitis Gram +ve Atypicals Skin & Chest Chest and Pneumonia genito-urinary Sinusitis Pneumonia Cellulitis Urethritis Wound infection PID Line infection (Osteomyelitis) Antibiotic spectrum Legionella, Streptococcus Anaerobic Chlamy dia & Bacteroides Pseudomonas pneumoniae & Streptococci Mycoplasma fragilis aeruginosa Group A, B, C, G &Clostridia pneumoniae Gram positive Gram negative Atypicals MRSA Staphylococci Streptococci EF Anaerobes Coliforms Resp Pyo ESBL Antibiotic Enterococcus Respiratory Extended- MRSA and Gut faecalis & Gram -ve e.g. spectrum beta- Coagulase- bacteria Enterococcus Haemophilus lactamase negative Staph. e.g. EliE. coli faecium influenzae & producers & other Moraxella resistant Gram catarrhalis negatives Green = Generally Sensitive; Orange = Unreliable; Red = Generally Resistant 1. Narrow-spectrum Gram-positive agents (Staphs and Streps) • Penicillin V/G*, Flucloxacillin • Erythromycin • Clindamycin • Fusidic acid, Rifampicin • Vancomycin, Teicoplanin MRSA cover • Linezolid • Daptomycin * No Staph aureus cover Gram-positive cover Antibiotic Gram Positive Gram Negative Atypicals MRSA Staph Strep Streptococci EF Anaerobes Resp Coliforms Pyo ESBL pneumo Benzylpen / RR G G GGAA R RR R Pen ic illin V Flucloxacillin RG G G RRRR R RR R Cefalexin RG G G RARR A RR R Vancomycin & GG G G GGRR R RR R Teicoplanin Linezolid GG G G GGAA R RR R Daptomycin* GG R*G GGRR R RR R Septrin® GG G G GRRA A AA Clarithromycin RG G A RARG R RR G Clindamycin RG G G RGAR R RR A *Inactive in the lung 2. Narrow-spectrum Gram-negative agents • Ciprofloxacin • Gentamicin, Tobramicin, Amikacin • Ceftazidime • Aztreonam • Colistin All active against pseudomonas Gram-negative cover Antibiotic Gram Positive Gram Negative Atypicals MRSA Staph Strep Streptococci EF Anaerobes Resp Coliforms Pyo ESBL pneumo Nitrofurantoin* GG G G GRRR G RG R Ciprofloxacin R A A A R R R G G G A G Gentamicin / AG R R ARRG G GG R Tobramycin / Amikacin Ceftazidime RA A A RARG G GR R Aztreonam RR R R RRRG G GR R Colistin RR R R RRRG G GA R *Only active in urine 3. Anti-anaerobe agents • Metronidazole • Clindamycin • Co-amoxiclav (“above the diaphragm” ) • Piperacillin-tazobactam • Ertapenem, imipenem, meropenem • Moxifloxacin Anaerobic cover Antibiotic Gram Positive Gram Negative Atypicals MRSA Staph Strep Streptococci EF Anaerobes Resp Coliforms Pyo ESBL pneumo Metronidazole RR R R RGGR R RR R Clindamycin RG G G RGAR R RR A Co-amoxiclav RG G G GGAG G RR R Pip-taz RG G G GGAG G GA R Ertapenem RG G G AGGG G RG R Imipenem RG G G GGGG G GG R Meropenem R G G G A G G G G G G R Tigecycline GG G G GGGG G RR G Moxifloxacin AG G G GGGG G RA G 4. Anti-atypical agents • Macrolides – erythromycin, clarithromycin etc. • Tetracyclines – oxytetracycline, doxycycline etc. • Fluoroquinolones – ccpooac,ooac,eooaceciprofloxacin, ofloxacin, levofloxacin etc. Atypical cover AibiiAntibiotic GPiiGram Positive GNiGram Negative Atyp ica ls MRSA Staph Strep Streptococci EF Anaerobes Resp Coliforms Pyo ESBL pneumo Tetracyclines DliDoxycycline G G G A R G A G A R A G Minocycline GG G G RGAG A RA G Tigecycline GG G G GGGG G RR G Macrolides Erythromycin RA G A RARA R RR G Clarithromycin RG G A RARG R RR G AithAzithromyc in R G G A R A R G A R R G Chlor- GG G G AGGG G RA G amphenicol Ciprofloxacin RA A A RRRG G GA G Levofloxacin RG G G GAAG G GA G Moxifloxacin AG G G GGGG G RA G Broad spectrum cover Antibiotic Gram Positive Gram Negative Atypicals MRSA Staph Strep Streptococci EF Anaerobes Resp Coliforms Pyo ESBL pneumo Co-amoxiclav RG G G GGAG G RR R Cefuroxime RG G G RA RG G RR R Ceftriaxone & RG G G RARG G RR R Cefotaxime Timentin RG G G AGGG G GA R Pip-taz RG G G GGGG G GA R Ertapenem R G G G A G G G G R G R Imipenem RG G G GGGG G GG R Meropenem RG G G AGGG G GG R Chlor- GG G G AGGG G RA G amphenicol Levofloxacin RG G G GAAG G GA G Moxifloxacin AG G G GGGG G RA G Tigecycline GG G G GGGG G RR G Most important slide! Patient risk Low-risk patient High-risk patient \ •Mild-to-moderate infection •Severe or life-threatening infection PthPathogen •No prior antibiotics •No recent healthcare •Prior antibiotics group exposure •Healthcare exposure •NhitNo history o f mu lti-resitistan t •His tory o f mu lti-resitistan t pathogens pathogens Gram +ve Flucloxacillin or Vancomycin or Linezolid Clarithromycin or (MRSA cover) Doxycycline Gram –ve Trimethopp,rim, Co-amoxiclav, Gentamicin or Pip-taz Doxycycline, Ciprofloxacin Anaerobe Metronidazole or Co- Metronidazole or Pip-taz amoxiclav Atypical Doxycycline or IV Clarithromycin or Clarithromycin Ciprofloxacin Treatment failure? Is your patient circling the DRAInS • D = Dose – Is the d ose ad equat e? I s th e pati ent getti ng d oses? • R = Resistance – MRSA, Clostridium difficile, ESBL-ppgroducing Gram-negative – Virus, fungi, TB, parasite (malaria, opportunistic infection) • A = Allergy – Drug fever = unexplained fever despite improvement of other symptoms and CRP/WBC • In = Interaction – e.g. doxycycline absorption reduced by up to 90% by iron • S = SOURCE CONTROL – Antibiotic therapy alone may not cure infection – Incision & drainage, debridement, removal of line or prosthetic device Thank you for your attention Happy to answer questions [email protected] Microbiota Antibiotics alter epithelial homeostasis in the gut and enhance host susceptibility to incoming pathogens Willing BP Nature Reviews Microbiology 2011 Nature Reviews Microbiology: April 2011 The average child in a developed country has received 10-20 courses o f an tibio tics by the age o f 18.