Potential Conflicts of Interest. Schematic. Reporting AST. Clinically-Oriented AST Reporting & Antimicrobial Stewardship

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Potential Conflicts of Interest Clinically-Oriented AST Reporting & Antimicrobial Stewardship Hsu Li Yang 27 th September 2013 Research Funding: Pfizer Singapore AstraZeneca Janssen-Cilag Merck, Sharpe & Dohme Advisory Board: Doripenem (Janssen-Cilag) Adult pneumococcal vaccine & Tigecycline (Pfizer) Conference sponsorships: Pfizer Singapore Janssen-Cilag Merck, Sharpe & Dohme Reporting AST Schematic Results that impact clinician antimicrobial prescribing and make a difference in patient outcomes. Time Resistance results Caveats against certain drugs Evidence-based guidance

Time to Antibiotics Susceptibility Results Blood culture: MRSA PENICILLIN R AMPICILLIN R CLOXACILLIN R CEPHALOTHIN R GENTAMICIN S COTRIMOXAZOLE S CLINDAMYCIN R VANCOMYCIN S CIPROFLOXACIN S FUSIDIC ACID S RIFAMPICIN S Susceptibility Results (1) Blood culture: MRSA PENICILLIN R AMPICILLIN R CLOXACILLIN R CEPHALOTHIN R GENTAMICIN S COTRIMOXAZOLE S CLINDAMYCIN R VANCOMYCIN S CIPROFLOXACIN S RIFAMPICIN S Susceptibility Results (2) Blood culture: Enterobacter cloacae AMPICILLIN R AMPICILLIN/SULBACTAM S CEFTRIAXONE S PIPERACILLIN/TAZOBACTAM S IMIPENEM S GENTAMICIN S COTRIMOXAZOLE S CIPROFLOXACIN S Comment: intrinsic and inducible ampc production cephalosporinsand penicillinsnot recommended for treatment of severe infections

Susceptibility Results (3) Blood culture: Enterobacter cloacae AMPICILLIN R AMPICILLIN/SULBACTAM S CEFTRIAXONE R PIPERACILLIN/TAZOBACTAM S IMIPENEM S GENTAMICIN S COTRIMOXAZOLE S CIPROFLOXACIN S Comment: intrinsic and inducible ampc production cephalosporinsand penicillinsnot recommended for treatment of severe infections Susceptibility Results (4) Blood culture: MRSA COTRIMOXAZOLE S VANCOMYCIN S Message: This is not to be regarded as a contaminant. The optimal antibiotics according to current guidelines are IV Vancomycinor IV Daptomycin(in the absence of MRSA pneumonia). Please repeat blood cultures and exclude endocarditis by echocardiography. Ability to Prevent and/or Treat Bacterial Infections is a Building Block of Medicine Intermission Images from the Internet (including http://www.nature.com).

Treatment Spectrum Treatment Spectrum Physician Risk-Aversion Practices Adverse Outcome Optimal Treatment - Mortality/Morbidity - Higher cost/stay - Antibiotic resistance - Drug adverse effects Narrower-Spectrum Antibiotics Broader-Spectrum Antibiotics Narrower-Spectrum Antibiotics Broader-Spectrum Antibiotics Shorter duration of antibiotics (Under-treatment) Longer duration of antibiotics (Over-treatment) Shorter duration of antibiotics (Under-treatment) Longer duration of antibiotics (Over-treatment) Broader is better Antibiotic Fallacies: Spiralling Empiricism Failure to respond is failure to cover Vicious Cycle of Antibiotics and Resistance New Broad- Spectrum Antibiotics When in doubt, change drugs or add another More diseases = more drugs Antibiotics are nontoxic Kim JH, et al. Am J Med. 1989;87:201-6. Higher Resistance Rates More Broad- Spectrum Antibiotics Prescribed Appropriate Empirical Therapy Saves Lives Rising Resistance Trends to Old Antibiotics

World Economic Forum 2013 Conserving Existing Antibiotics Antimicrobial Stewardship Global Risks 2013: Available at: http://www3.weforum.org/docs/wef_globalrisks_report_2013.pdf National Call for ASP ASP: Objectives Reduce inappropriate prescribing and use of antimicrobials. Reduce emergence of antimicrobial resistance. Reduce preventable adverse drug events and length of stay for patients due to infections. Improve cost-effective use of antimicrobials. Safety. Hsu LY, et al. Singapore Med J. 2008;49:749. Slide courtesy of MsChayLengYeo

Forms of Stewardship National University Hospital Prospective audit and feedback. Antibiotic restriction. Permission required for prescription Automatic stop orders Antibiotic cycling Other elements: Education of providers Guidelines Computerized clinical decision support Dellit, et al. Clin Infect Dis. 2007;44:159-77. ASP commenced July 2009. Singapore General Hospital Formal prospective audit and feedback ASP in 2008. - IV to PO switch - Recommendation for duration of therapy

Summary of data Patient is on ceftriaxone ARUS-C recommends 2 weeks of IV Ampicillin ARUS-C helps you stop Ceftriaxone unless you want to keep by over-riding ARUS-C Click on ARUS-C guidance button ARUS-C History contains selected patient s ARUS-C record ARUS-C briefly updates you on the ID condition Issues and Barriers Sustainability of current AS programs. Financial Personnel: passion and career tracks Barriers: Prescribing Etiquette Non-interference with prescribing decisions of colleagues: Autonomous decision of prescribing. Accepted non-compliance to policy: Hierarchy and expertise (not policy) as determinants of prescribing behavior. Hierarchy of prescribing: Senior doctors decide, junior doctors prescribe. Continued opposition from prescribers due to perceived challenge to autonomy. Lack of awareness and adherence to guidelines and clinical pathways. CharaniE, et al. Clin Infect Dis. 2013. In press.

Thank You! Email: hsuliyang@gmail.com Antibiotic Resistance Surveillance: Cumulative Antibiogram & Software for Resistance Surveillance Hsu Li Yang 27 th September 2013 Potential Conflicts of Interest Research Funding: Pfizer Singapore AstraZeneca Janssen-Cilag Merck, Sharpe & Dohme Advisory Board: Doripenem (Janssen-Cilag) Adult pneumococcal vaccine & Tigecycline (Pfizer) Conference sponsorships: Pfizer Singapore Janssen-Cilag Merck, Sharpe & Dohme Why Perform Surveillance Monitor trends in resistance and prescription. Try to correlate the above. Helps guide empirical antibiotic therapy. Define thresholds for interventions. Detect emergence of new resistant pathogens. O'Brien TF, Stelling J. Integrated Multilevel Surveillance of the World's Infecting Microbes and Their Resistance to Antimicrobial Agents. Clin Microbiol Rev. 2011; 24: 281-295.

Alphabet Soup of Resistance Multidrug-resistant (MDR): Acquired non-susceptibility to 3 or more antibiotic categories. Extensively drug-resistant (XDR): Non-susceptibility to all but 2 or fewer antibiotic categories. Pandrug-resistant (PDR): Resistant to all drugs in all antibiotic categories. CRE Magiorakos AP, et al. ClinMicrobiol Infect. 2012;18:268-81. Acinetobacter baumannii

Carbapenems Carbapenems Correlation: Prescription/Resistance Antibiogram periodic summary of antimicrobial susceptibilities of local bacterial isolates Uses: 1. Assess local susceptibility rates 2. Guide to empiric therapy 3. Formulating guidelines & formulary 4. Monitoring resistance trends 5. Quality control tool

Antibiogram: limitations Representative population Duplicate patients / isolates Isolates, not infection Aggregate data may not reflect local data No clinical data Ciprofloxacin & E. coli: by age 100% 90% 80% 70% 60% 50% 40% 30% R I S 20% 10% 0% 0-10 11-20 21-30 31-40 41-50 51-60 61-70 >70 Age range

Quality control Guidance documents Boehme MS et al. Systematic Review of Antibiograms: A National Laboratory System Approach for Improving Antimicrobial Susceptibility Testing Practices in Michigan. Public Health Rep. 2010; 125(Suppl 2): 63 72. Hindler, J. F., & Stelling, J. (2007). Analysis and presentation of cumulative antibiograms: a new consensus guideline from the Clinical and Laboratory Standards Institute. Clinical Infectious Diseases, 44(6), 867-873. Guidance 1. definitions for classifying isolates as clinically relevant or as contaminants 2. definitions of duplicate isolates 3. procedures for eliminating contaminant and duplicate isolates from data sets 4. criteria for classifying isolates as susceptible or resistant on the basis of current published criteria 5. criteria to define and separate isolates recovered from inpatients from those recovered from outpatients 6. criteria for the minimal number of isolates necessary for statistical analysis. Laboratory Information System Tools Wilson ML. Assuring the Quality of Clinical Microbiology Test Results. Clin Infect Dis. 2008; 47: 1077-1082.

Tools Tools Laboratory Information System Laboratory Information System Baclink: Capture and standardizing of data from existing information systems. WHONET: Desktop application for the entry and analysis of microbiology data. WHONET Software WHONET Software

WHONET Software WHONET Software WHONET Software Who gives a d**n? 74% used Sanford Guide antibiograms 64% never used hospital antibiogram 61% did not know where to find hospital antibiogram Mermel LA, Jefferson J, Devolve J. Knowledge and Use of Cumulative Antimicrobial Susceptibility Data at a University Teaching Hospital. Clin Infect Dis. 2008; 46: 1789-1789.

Thank You! Email: hsuliyang@gmail.com