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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)

3 www.who.int/drugresistance



AMR is a Public Health Threat

4

www.cdc.gov


PublicHealthOntario.ca 5

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



AMR as a Global Priority

6

www.who.int



Clostridium difficile is an Urgent Threat

7

www.cdc.gov


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



Overuse of Antimicrobials

9 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.

www.cdc.gov



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”

10

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

Image credit: iStock / Getty Images Plus /Getty Images


http://www.jstor.org/stable/10.1086/665010


Benefits of Antimicrobial Stewardship

Improved patient outcomes

Reduced adverse events

Reduced C. difficile infections

Improvement in antimicrobial susceptibility

Optimization of resource utilization

11

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


http://cid.oxfordjournals.org/content/62/10/e51


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

13 www.publichealthontario.ca/ASP


PublicHealthOntario.ca 14

www.publichealthontario.ca/ASP



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



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

Institute for Quality Management in Healthcare

(IQMH) – Consensus Practice Recommendations -

Antimicrobial Susceptibility Testing and Reporting

on Bacteriology Specimens – Dec 14, 2016



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

Group B – Optional Primary Test, Report Selectively

Group C – Supplemental, Report Selectively

Group U – Supplemental, For Urine Only

Ampicillin Cefazolin Gentamicin Tobramycin

Amikacin Amoxicillin-clavulanate Ampicillin-sulbactam Ceftolozane-tazobactam Piperacillin-tazobactam Cefuroxime Cefepime Cefotetan Cefoxitin Ceftriaxone or Cefotaxime Levofloxacin Ciprofloxacin Doripenem Ertapenem Imipenem Meropenem Trimethoprim-sulfamethoxazole

Aztreonam Ceftazidime Ceftaroline Chloramphenicol Tetracycline

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.”

23

Source: Thaler RH, Sunstein CR. Nudge: improving decisions about health, wealth and happiness. New Haven, CT: Yale University Press;2008.



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 Restricting reports to selected antimicrobials and providing further data on request only

Framing 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.)

25 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].



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

26

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.



Selective Reporting of Ciprofloxacin

Before After

27

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.



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

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

29

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

30




Results – Antibiotic Utilization

31

Trend DDD/1000

Patient

days/month

(95%

Confidence

Interval)

Level Effect Change in DDD/1000 Patient days

Compared to Predicted Based on Pre-Intervention Usage

(95% Confidence Interval)

Drug Change in

Slope

3 months

6 months 12 months 24 months

Ciprofloxacin -0.78* (-1.26 to -0.30)

-23.7* (-34.8 to -12.6)

-26.3* (-38.0 to -14.6)

-31.0* (-44.3 to -17.7)

-39.2* (-59.5 to -18.9)

Moxifloxacin -0.57* (-0.82 to -0.11)

3.8 (-12.0 to 4.3)

-5.2 (-13.8 to 3.4)

-7.8 (-17.6 to 2.0)

-12.8 (-27.7 to 2.13)

TMP-SMX -0.24* (-0.39 to -0.09)

-0.4 (-3.9 to 3.2)

-1.1 (-4.8 to 2.6)

0.2 (-4.5 to 4.0)

-7.0* (-13.4 to -0.6)

Nitrofurantoin -0.06 (-0.14 to 0.02)

1.8 (-0.1 to 3.7)

1.6 (-0.3 to 3.6)

1.3 (-1.0 to 3.5)

0.2 (-3.2 to 3.6)

Amoxicillin-

Clavulanate

0.654* (0.26 to 1.05)

8.8 (-0.2 to 17.8)

10.8* (1.3 to 20.3)

14.7* (3.9 to 25.5)

22.0* (5.4 to 38.5)

*P<0.05




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

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


36 PublicHealthOntario.ca

Image credit: paci77/Getty Images


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