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Antimicrobial Stewardship in the Microbiology Laboratory A Nudge Towards More Appropriate Antibiotic Use Jennie Johnstone, MD, PhD Bradley Langford, PharmD, BCPS Larissa Matukas, MD, MSc

Learning Objectives Define antimicrobial stewardship Explain why antimicrobial stewardship is a vital initiative to combat antimicrobial resistance Describe the role of selective antimicrobial susceptibility reporting in directing appropriate antimicrobial use 2

Antimicrobial Resistance (AMR) www.who.int/drugresistance 3

AMR is a Public Health Threat www.cdc.gov 4

The Review on Antimicrobial Resistance, Chaired by Jim O Neill 5

AMR as a Global Priority www.who.int 6

Clostridium difficile is an Urgent Threat www.cdc.gov 7

Source: Poutanen SM, Simor AE. Clostridium difficile-associated diarrhea in adults. CMAJ. 2004;171(1):51-8.

Overuse of Antimicrobials www.cdc.gov Source: Fleming-Dutra K, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits 2010-2011. JAMA. 2016;315(17):1864-73. 9

What is Antimicrobial Stewardship? coordinated interventions designed to improve and measure the appropriate use of [antibiotic] agents by promoting the selection of the optimal [antibiotic] drug regimen including dosing, duration of therapy, and route of administration Image credit: istock / Getty Images Plus /Getty Images Source: Society for Healthcare Epidemiology of America, Infection Control & Hospital Epidemiology,Pediatric Infectious Diseases Society. Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infect Control Hosp Epidemiol. 2012;33(4):322-7. Available from: http://www.jstor.org/stable/10.1086/665010 Image credit: Public Health Ontario, 2016 10

Benefits of Antimicrobial Stewardship Improved patient outcomes Reduced adverse events Reduced C. difficile infections Improvement in antimicrobial susceptibility Optimization of resource utilization Source: Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016; 62: e51 77. Available from: http://cid.oxfordjournals.org/content/62/10/e51 11

Antimicrobial Stewardship at PHO Provide tools, resources and expertise to help advance antimicrobial stewardship in all sectors across Ontario Engages in research and evaluation of antimicrobial stewardship activities across the province 12

32 Antimicrobial Stewardship Strategies www.publichealthontario.ca/asp 13

www.publichealthontario.ca/asp 14

Cascading Antimicrobial Susceptibility Reporting 15

Institute for Quality Management in Healthcare (IQMH) Consensus Practice Recommendations - Antimicrobial Susceptibility Testing and Reporting on Bacteriology Specimens Dec 14, 2016 Laboratories are strongly encouraged to incorporate some form of selective antimicrobial reporting. Each laboratory should decide which agents to report routinely and which should be reported only selectively. Selective or cascade antimicrobial reporting plays an indirect role in antimicrobial stewardship programs, by minimizing the selection of multi-drug resistant organisms through overuse of broad-spectrum agents. 16

Institute for Quality Management in Healthcare (IQMH) Consensus Practice Recommendations - Antimicrobial Susceptibility Testing and Reporting on Bacteriology Specimens Dec 14, 2016 When reviewing antibiotic reporting cascades, laboratories should consider the benefit of having representation of antimicrobials from at least two differing classes to which the organism is susceptible (whenever possible), which will provide the clinician with more treatment choices for patients with drug allergies and for patients in whom drug interactions may be an issue. 17

Clinical Laboratory Standards Institute (CLSI) M100 S26: Performance Standards for Antimicrobial Susceptibility Testing Selection of the most appropriate antimicrobial agent to test and to report is a decision best made by each laboratory in consultation with the infectious diseases practitioners and the pharmacy, as well as the pharmacy and therapeutic and infection control committees of the medical staff. 18

Suggested Groupings of Antimicrobial Agents with FDA Clinical Indications - Enterobacteriaceae Group A Primary Test & Report Ampicillin Cefazolin Gentamicin Tobramycin Group B Optional Primary Test, Report Selectively Amikacin Amoxicillin-clavulanate Ampicillin-sulbactam Ceftolozane-tazobactam Piperacillin-tazobactam Cefuroxime Cefepime Cefotetan Cefoxitin Ceftriaxone or Cefotaxime Levofloxacin Ciprofloxacin Doripenem Ertapenem Imipenem Meropenem Trimethoprim-sulfamethoxazole Group C Supplemental, Report Selectively Aztreonam Ceftazidime Ceftaroline Chloramphenicol Tetracycline Group U Supplemental, For Urine Only Cefazolin (surrogate for uncomplicated UTI) Fosfomycin Norfloxacin Nitrofurantoin Sulfisoxazole Trimethoprim 19

Challenges of Selective/Cascading Reporting Variability in reporting from one lab to another based on availability of expertise and degree of collaboration Initially labour-intensive to set rules for reports, additionally resource intensive if not automated in lab information system Unnecessary broad-spectrum prescriptions may continue if cascading algorithms are based on cost alone Misinterpretation that an unlisted antimicrobial equals resistance Use of specific cascade reporting algorithms may be more difficult, expensive or even impossible if an institution s microbiology laboratory services are outsourced 20

Requirements for Success Collaborative relationship between the antimicrobial stewardship team, microbiologist and microbiology laboratory and other key healthcare providers Automation of cascading rules/algorithm Regular review of cascading rules and choice of reported antimicrobial susceptibilities. Education of health care professionals on interpretation of the reports and knowing when to call the microbiology laboratory for additional susceptibilities. 21

What Does Success Look Like? unnecessarily broad-spectrum, expensive and/or more toxic antimicrobials antimicrobial resistance antimicrobial stewardship prospective audit and feedback interventions C. difficile infections 22

Thaler and Sunstein s Nudge: Improving Decisions about Health, Wealth & Happiness Defines a Nudge as: A nudge, as we will use the term, is any aspect of the choice architecture that alters people s behavior in a predictable way without forbidding any options or significantly changing their economic incentives. To count as a mere nudge, the intervention must be easy and cheap to avoid. Source: Thaler RH, Sunstein CR. Nudge: improving decisions about health, wealth and happiness. New Haven, CT: Yale University Press;2008. 23

What do Cheerios and Flies Have in Common? They both steer behaviour to aim into the toilet and not onto the floor Decals of flies placed near the drains of urinals, resulted in ~80% reduction of spillage on the bathroom floor 24

Nudging in Microbiological Reports: A Strategy to Improve Prescribing Nudge strategy Possible use in microbiological reporting Putting choices at eye level Emphasizing certain antimicrobials by using bold or larger font and/or placing them at the top of the list ( at eye level ) Default choice Framing Restricting reports to selected antimicrobials and providing further data on request only Changing the context of data presentation, e.g. by providing interpretation (colonization versus infection) or information on substances (broad or narrow spectrum, pharmacokinetics, adverse events, costs, etc.) Source: Katchanov J, Kluge S, MacKenzie CR, Kaasch AJ. Nudging in microbiological reports: a strategy to improve prescribing. Infection. 2016 Aug 19 [Epub ahead of print]. 25

Background/Rationale St. Joseph s Health Centre 400 Bed Community Teaching Hospital in Toronto Target fluoroquinolones High usage C. difficile Infections/Outbreaks High rates of resistance In February 2011, we initiated a selective reporting policy aimed at reducing use of fluoroquinolones Langford BJ, Seah J, Chan A, Downing M, Johnstone J, Matukas LM. Antimicrobial stewardship in the microbiology laboratory: impact of selective susceptibility reporting on ciprofloxacin utilization and susceptibility of gram-negative isolates to ciprofloxacin in a hospital setting. J Clin Microbiol. 2016;54(9):2343-7. 26

Selective Reporting of Ciprofloxacin Before After Source: Langford BJ, Seah J, Chan A, Downing M, Johnstone J, Matukas LM. Antimicrobial stewardship in the microbiology laboratory: impact of selective susceptibility reporting on ciprofloxacin utilization and susceptibility of gram-negative isolates to ciprofloxacin in a hospital setting. J Clin Microbiol. 2016;54(9):2343-7. 27

Methods Primary Outcome: Antibiotic Use Per 1000 Patient Days (measured in Defined Daily Doses) Ciprofloxacin Moxifloxacin TMP-SMX Nitrofurantoin Amoxicillin-Clavulanate Secondary Outcome: % Susceptibility to Ciprofloxacin E. coli P. aeruginosa Source: Langford BJ, Seah J, Chan A, Downing M, Johnstone J, Matukas LM. Antimicrobial stewardship in the microbiology laboratory: impact of selective susceptibility reporting on ciprofloxacin utilization and susceptibility of gram-negative isolates to ciprofloxacin in a hospital setting. J Clin Microbiol. 2016;54(9):2343-7. 28

Statistical Methods Interrupted time series (ITS) with segmented regression Autoregressive integrated moving average (ARIMA) models were generated Slope/Trend, Pre/Post Level compared to predicted post-intervention: 1 month 3 months 6 months 12 months 24 months Source: Langford BJ, Seah J, Chan A, Downing M, Johnstone J, Matukas LM. Antimicrobial stewardship in the microbiology laboratory: impact of selective susceptibility reporting on ciprofloxacin utilization and susceptibility of gram-negative isolates to ciprofloxacin in a hospital setting. J Clin Microbiol. 2016;54(9):2343-7. 29

Results Antibiotic Utilization Source: Langford BJ, Seah J, Chan A, Downing M, Johnstone J, Matukas LM. Antimicrobial stewardship in the microbiology laboratory: impact of selective susceptibility reporting on ciprofloxacin utilization and susceptibility of gram-negative isolates to ciprofloxacin in a hospital setting. J Clin Microbiol. 2016;54(9):2343-7. 30

Source: Langford BJ, Seah J, Chan A, Downing M, Johnstone J, Matukas LM. Antimicrobial stewardship in the microbiology laboratory: impact of selective susceptibility reporting on ciprofloxacin utilization and susceptibility of gram-negative isolates to ciprofloxacin in a hospital setting. J Clin Microbiol. 2016;54(9):2343-7. Results Antibiotic Utilization Drug Trend DDD/1000 Patient days/month (95% Confidence Interval) Change in Slope Ciprofloxacin -0.78* (-1.26 to -0.30) Moxifloxacin -0.57* (-0.82 to -0.11) TMP-SMX -0.24* (-0.39 to -0.09) Nitrofurantoin -0.06 (-0.14 to 0.02) Amoxicillin- Clavulanate *P<0.05 0.654* (0.26 to 1.05) Level Effect Change in DDD/1000 Patient days Compared to Predicted Based on Pre-Intervention Usage (95% Confidence Interval) 3 months 6 months 12 months 24 months -23.7* (-34.8 to -12.6) 3.8 (-12.0 to 4.3) -0.4 (-3.9 to 3.2) 1.8 (-0.1 to 3.7) 8.8 (-0.2 to 17.8) -26.3* (-38.0 to -14.6) -5.2 (-13.8 to 3.4) -1.1 (-4.8 to 2.6) 1.6 (-0.3 to 3.6) 10.8* (1.3 to 20.3) -31.0* (-44.3 to -17.7) -7.8 (-17.6 to 2.0) 0.2 (-4.5 to 4.0) 1.3 (-1.0 to 3.5) 14.7* (3.9 to 25.5) -39.2* (-59.5 to -18.9) -12.8 (-27.7 to 2.13) -7.0* (-13.4 to -0.6) 0.2 (-3.2 to 3.6) 22.0* (5.4 to 38.5) 31

Source: Langford BJ, Seah J, Chan A, Downing M, Johnstone J, Matukas LM. Antimicrobial stewardship in the microbiology laboratory: impact of selective susceptibility reporting on ciprofloxacin utilization and susceptibility of gram-negative isolates to ciprofloxacin in a hospital setting. J Clin Microbiol. 2016;54(9):2343-7. Results Antibiotic Susceptibility 32

Discussion Strengths Rigorous assessment of selective reporting as part of an ASP Reduced fluoroquinolone use Reduced resistance Address class of antimicrobial with significant risk of harm (fluoroquinolones) Limitations Numerous confounders Non-automated process Generalizable to urinary cultures Squeezing the balloon : shift of antibiotic use from one class to another Source: Langford BJ, Seah J, Chan A, Downing M, Johnstone J, Matukas LM. Antimicrobial stewardship in the microbiology laboratory: impact of selective susceptibility reporting on ciprofloxacin utilization and susceptibility of gram-negative isolates to ciprofloxacin in a hospital setting. J Clin Microbiol. 2016;54(9):2343-7. 33

Conclusion Antimicrobial stewardship is an important way to mitigate the public health threat of antimicrobial resistance. Selective/cascading reporting of microbiology results is one approach to help nudge prescribers to select more appropriate antimicrobial therapy. A collaborative approach to presenting microbiology results, in combination with a broader antimicrobial stewardship program, may help reduce targeted antimicrobial utilization and slow the emergence of antimicrobial resistance. 34

Next Steps Review best practice recommendations for selective reporting and other reporting strategies - PHO ASP website, IQMH, CLSI Collaborating with stakeholders Microbiology Pharmacy Antimicrobial Stewardship Infection Prevention and Control Laboratory Information System Other healthcare professionals Patients Monitor the outcomes 35

Image credit: paci77/getty Images 36