Rational Prescribing and its Effect on Antimicrobial Resistance

Daniel VanderEnde, MD, MPH, DTM&H

Medical Officer, US Centers for Disease Control

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DPHICON-2022

December 8^th, 2022

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National Center for Emerging and Zoonotic Infectious Diseases

Antibiotic Use Leads to the Development and Spread of Antibiotic Resistance

Antibiotic Use Increases the Patient’s Odds of Harboring Antibiotic-Resistant Bacteria

• Five studies demonstrated increased odds of having antibiotic-resistant urinary Escherichia coli at 2 months and 12 months following antibiotic treatment.
• Pooled odds ratios (ORs):
• 2 months OR = 2.5 (95% confidence interval (CI): 2.1 to 2.9)
• 12 months OR = 1.33 (95% CI: 1.2 to 1.5)

Constelloe, C., et al. (2010). BMJ 340: c2096

Antibiotic Use Increases the Patient’s Odds of Harboring Antibiotic-Resistant Bacteria (cont.)

• Seven studies observed increased odds of having antibiotic resistance among respiratory tract bacteria at 2 and 12 months following antibiotic treatment
• Pooled ORs:
• 2 months OR = 2.4 (95% CI: 1.4 to 3.9)
• 12 months OR = 2.4 (95% CI: 1.3 to 4.5)

Constelloe, C., et al. (2010). BMJ 340: c2096

This Photo by Unknown Author is licensed under CC BY-SA-NC

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Antibiotic Resistance

• Antibiotic use leads to the development of antibiotic resistance
• About 30% of antibiotics are prescribed unnecessarily or inappropriately
• Up to 30% of all surgical prophylaxis is inappropriate

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Klein, E.Y., et al. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. PNAS. 2018.

https://iamrsn.icmr.org.in/images/pdf/AMSP_Guidelines_final.pdf

Articles from India

Impact of Antibiotic Resistance

• Patients with resistant infections often have higher mortality, worse outcomes (e.g., longer hospital stays), and higher healthcare costs
• When a patient is infected with antibiotic-resistant bacteria, healthcare providers may need to use antibiotics that are less effective and associated with more adverse events

Global Deaths Attributable to Bacterial Antimicrobial Resistance by Pathogen-Drug Combination

• In a 2019 global study, nearly 1.3 million deaths were attributable to bacterial antimicrobial resistance
• 5 drugs attributable to over 100,000 deaths each amongst all pathogens
• Third generation cephalosporins
• Carbapenems
• Fluoroquinolones
• Methicillin
• Trimethoprim-sulfamethoxazole

Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 202; 399: 629-55.

Antibiotic Use Can be Safely Improved Through Antibiotic Stewardship

Implementing Antibiotic Stewardship is Associated with Reduced Mortality in Hospitals

• A 2016 review and meta-analysis examined 145 studies to assess the effect of implementing antibiotic stewardship interventions on clinical outcomes, including mortality
• Interventions included:
• Increasing adherence to guidelines
• De-escalation of antibiotic therapy

Schuts, E.C., et al. (2016). Lancet Infect Dis.

Implementing Antibiotic Stewardship is Associated with Reduced Mortality in Hospitals (contin.)

• Increasing adherence to guidelines for empiric antibiotic prescribing was associated with a 35% relative risk reduction in mortality
• Relative risk of mortality = 0.65 (95% CI: 0.54 to 0.80)
• De-escalation of antibiotic therapy was associated with a 56% relative risk reduction in mortality
• Relative risk of mortality = 0.44 (95% CI: 0.30 to 0.66)

Schuts, E.C., et al. (2016). Lancet Infect Dis.

Study: Implementation of an Antimicrobial Stewardship Program in South Africa

• Implementation in 47 urban and rural hospitals in South Africa using existing resources to assess the reduction of overall antibiotic consumption
• Pharmacist-driven antimicrobial stewardship initiative
• Significant overall reduction in antibiotic daily defined doses per 100 patient-days (18.1%; 95% CI 16.71%-20.4%)

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Adrian J Brink et al The Lancet Infectious Diseases, Vol 16, Issue 9, 2016, pp. 1017-1025

Decreased Antibiotic Use Associated with Lower Rates of Methicillin-Resistant Staphylococcus aureus (MRSA) in Hospitals and in the Community

• The programs contributed to reductions in use of cephalosporins, amoxicillin-clavulanate, clindamycin, fluoroquinolones, and macrolides by 47% in hospitals and 27% in the community
• MRSA prevalence decreased by 54% in hospitals and 37% in the community¹
• Meta-analysis of published studies found patients with MRSA bacteremia had an increased risk of mortality compared with methicillin susceptible Staphylococcus aureus (MSSA)²

1. Lawes, T., et al. (2015). Lancet Infect Dis. 15(12): 1438-1449.

2. Zacharioudakis IM, et al (2014) J Am Soc Nephrol. 25(9):2131-2141.

Decreased Use of Fluoroquinolones and Cephalosporins Associated with Decreased Hospital-Level Escherichia coli Resistance

• A retrospective controlled interrupted time-series examined the effect of implementation of a hospital-based stewardship program on E. coli antibiotic resistance between 2008 to 2014
• Two academic hospitals were examined – one with an antibiotic stewardship program and one without a program
• The experimental group, in comparison with the control, showed a decrease in cephalosporin (-151 fewer defined daily doses) and fluoroquinolones (-44.5 fewer defined daily doses) use
• A significant improvement in the slope of E. coli resistance over time to fluoroquinolones and cephalosporins was also observed in the experimental group

Boel, J., et al. (2016). J Antimicrob Chemother. 71(7): 2047-2051

Appropriate use of Antibiotics reduced mortality

Rural Maharashtra

• Home-based newborn care by trained village health workers.
• Included assessment for possible serious bacterial infection and pre-referral administration of injectable gentamicin.
• Intervention resulted
• 16% decrease in neonatal sepsis case fatality
• 62% reduction in all-cause neonatal mortality.

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Bang AT, et al. . Lancet 1999; 354: 1955–61.

Case Study: A Facility Outbreak Led to the Establishment of a Facility Antimicrobial Stewardship Program – Barbados

• 600-bed healthcare facility in Barbados had an outbreak of carbapenemase-resistant Klebsiella pneumoniae (KPC)
• IPC team used data to demonstrate to hospital management that an antimicrobial stewardship program was critically needed
• Facility saw a 60% decline in the use of carbapenems and vancomycin

Forde C, et al. PLoS One. 2017;12(5):e0176779.

AMSP implementation leads to reduced costs

Antibiotic Stewardship Interventions Can Safely Reduce Antibiotic Use

• A 2017 meta-analysis of 221 studies, including 58 randomized controlled trials, examined the effects of interventions to improve antibiotic prescribing among hospitalized patients
• Antibiotic stewardship interventions reduced antibiotic treatment by 1.95 days (95% CI: 1.67 to 2.22)
• Less antibiotic use did not increase mortality (Risk difference = 0%; 95% CI: -1% to 0%)
• Antibiotic stewardship interventions may reduce length of stay by 1.12 days (95% CI: 0.70 to 1.54 days)

Davey, P., et al. (2017). Cochrane Database Syst Rev. (2).

There Are Opportunities to Improve Antibiotic Use

Antibiotic Stewardship

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The coordinated intervention designed to improve and measure the appropriate use of antimicrobial agents, by promoting the selection of optimal antimicrobial drug regimen including dosing, duration of therapy and route of administration

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Policy statement on antimicrobial stewardship SHEA, IDSA, and PIDS. Infect Control Hosp Epidemiol. 2012;33(4):322-327.

WHO Healthcare Facility Core Elements for Antimicrobial Stewardship Programs in LMICs

WHO Practical toolkit. 2019. https://apps.who.int/iris/handle/10665/329404

WHO Practical Toolkit

• Built to support countries based on the Global Action Plan
• Provides practical guidance on how to implement antimicrobial stewardship programs

WHO Practical toolkit. 2019. https://apps.who.int/iris/handle/10665/329404

Planning an Antimicrobial Stewardship Program in a Healthcare Facility

WHO Practical toolkit. 2019. https://apps.who.int/iris/handle/10665/329404

Core Elements of Human Antibiotic Stewardship Programs in Resource-Limited Settings | Antibiotic Use | CDC

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WHO – Basic AMS Interventions

WHO Practical toolkit. 2019. https://apps.who.int/iris/handle/10665/329404

Five Core Actions to Combat Antibiotic Resistance

For more information, contact CDC�1-800-CDC-INFO (232-4636)�TTY: 1-888-232-6348 www.cdc.gov���The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.