Potential Conflicts of Interest

Research Funding:

Clinically-Oriented AST Reporting & Antimicrobial Stewardship

Hsu Li Yang 27th September 2013

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
Results that impact clinician antimicrobial prescribing and make a difference in patient outcomes.
Time Resistance results Caveats against certain drugs Evidence-based guidance

Schematic

Time to Antibiotics

Susceptibility Results
Blood culture: MRSA
PENICILLIN AMPICILLIN CLOXACILLIN CEPHALOTHIN GENTAMICIN COTRIMOXAZOLE CLINDAMYCIN VANCOMYCIN CIPROFLOXACIN FUSIDIC ACID RIFAMPICIN R R R R S S R S S S S

Susceptibility Results (1)

Blood culture: MRSA
PENICILLIN AMPICILLIN CLOXACILLIN CEPHALOTHIN GENTAMICIN COTRIMOXAZOLE CLINDAMYCIN VANCOMYCIN CIPROFLOXACIN RIFAMPICIN R R R R S S R S S S

Susceptibility Results (2)

Blood culture: Enterobacter cloacae
AMPICILLIN AMPICILLIN/SULBACTAM CEFTRIAXONE PIPERACILLIN/TAZOBACTAM IMIPENEM GENTAMICIN COTRIMOXAZOLE CIPROFLOXACIN R S S S S S S S

Comment: intrinsic and inducible ampC production cephalosporins and penicillins not recommended for treatment of severe infections

Susceptibility Results (3)

Blood culture: Enterobacter cloacae
AMPICILLIN AMPICILLIN/SULBACTAM CEFTRIAXONE PIPERACILLIN/TAZOBACTAM IMIPENEM GENTAMICIN COTRIMOXAZOLE CIPROFLOXACIN R S R S S S S S

Susceptibility Results (4)

Blood culture: MRSA
COTRIMOXAZOLE VANCOMYCIN S S

Comment: intrinsic and inducible ampC production cephalosporins and penicillins not recommended for treatment of severe infections

Message: This is not to be regarded as a contaminant. The optimal antibiotics according to current guidelines are IV Vancomycin or 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
Physician Risk-Aversion Practices

Treatment Spectrum

Adverse Outcome
Mortality/Morbidity Higher cost/stay Antibiotic resistance Drug adverse effects Broader-Spectrum Antibiotics

Optimal Treatment Narrower-Spectrum Antibiotics Broader-Spectrum Antibiotics

Narrower-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)

Antibiotic Fallacies: Spiralling Empiricism

Broader is better Failure to respond is failure to cover 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.

Vicious Cycle of Antibiotics and Resistance

New BroadSpectrum Antibiotics

Higher Resistance Rates

Rising Resistance Trends to Old Antibiotics

More BroadSpectrum Antibiotics Prescribed

Appropriate Empirical Therapy Saves Lives

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 Ms Chay Leng Yeo

Forms of Stewardship
Prospective audit and feedback. Antibiotic restriction.
Permission required for prescription
Automatic stop orders

National University Hospital

Antibiotic cycling

Other elements:
Education of providers Guidelines Computerized clinical decision support
ASP commenced July 2009.

Dellit, et al. Clin Infect Dis. 2007;44:159-77.

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 briefly updates you on the ID condition ARUS-C History contains selected patients ARUS-C record

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.
Charani E, 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 27th September 2013

Potential Conflicts of Interest

Research Funding:
Pfizer Singapore AstraZeneca 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.

Advisory Board:
Doripenem (Janssen-Cilag) Adult pneumococcal vaccine & Tigecycline (Pfizer)

Conference sponsorships:
Pfizer Singapore Janssen-Cilag Merck, Sharpe & Dohme

Alphabet Soup of Resistance

Multidrug-resistant (MDR):
Acquired non-susceptibility to 3 or more antibiotic categories.

Extensively drug-resistant (XDR): CRE

Non-susceptibility to all but 2 or fewer antibiotic categories.

Pandrug-resistant (PDR):
Resistant to all drugs in all antibiotic categories.
Magiorakos AP, et al. Clin Microbiol 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% 20% 10% 0% R I S

0-10 11-20 21-30 31-40 41-50 51-60 61-70 >70

Age range

Quality control

Guidance documents

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. 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): 6372.

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.
Wilson ML. Assuring the Quality of Clinical Microbiology Test Results. Clin Infect Dis. 2008; 47: 1077-1082.

Tools

Laboratory Information System

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% 64% 61% used Sanford Guide antibiograms never used hospital antibiogram 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