Spotlight on Antibiotic Stewardship

December 2022

Introduction

Antibiotics can curb a range of infections caused by bacteria, from some earaches to life-threatening sepsis. But their overuse or misuse by clinicians and patients hastens antimicrobial resistance, enabling harmful bacteria to better withstand curative drugs.

The Centers for Disease Control and Prevention estimates that about one-third of antibiotic prescriptions in the US are unnecessary^[1], and today, antibiotic resistance has become one of the world’s most pressing health problems, with a growing number of antibiotic treatments less effective against bacteria than they once were. Leading health and medical organizations have called on medical professionals around the world to practice antibiotic stewardship that reins in unnecessary or inappropriate antibiotic prescribing and use.

VA has long been committed to cutting-edge research and practice of antibiotic stewardship and infection prevention. HSR&D supports the Informatics, Decision-Enhancement and Analytic Sciences Center (IDEA), for example, which engages in research that helps combat drug resistance. Additionally, VA’s Quality Enhancement Research Initiative (QUERI) collaborates with VA facilities and providers nationwide to address antibiotic resistance through its CARRIAGE and RAISE programs, which work to reduce healthcare-associated infections.

Following are some HSR&D studies that focus on antibiotic resistance.

• Improving antimicrobial use at hospitals that lack infectious disease specialists
• Diagnostic stewardship as a "nudge" to reduce inappropriate antibiotic use for urinary tract infections
• Development of a stewardship intervention for CLC pharmacists to improve UTI treatments
• Less is more: Improving antimicrobial stewardship for asymptomatic bacteriuria

Improving antimicrobial use at hospitals that lack infectious disease specialists

Antimicrobial stewardship programs (ASPs) improve patient safety and reduce antimicrobial resistance—which has reached crisis levels—by ensuring that patients receive the right antimicrobial at the right dose and for the right duration. VHA Directive 1031 mandated that every VA medical facility establish and maintain an ASP, and similar regulations have been implemented in non-VA settings.

Though robust ASPs play an essential role in addressing antimicrobial resistance, widespread ASP implementation is challenging, particularly because many ASPs lack access to infectious disease (ID) specialists, including 23% of VA ASPs. It is unclear how ASPs can be effective in such resource-limited settings.

About this research

The primary goal of this project was to evaluate and improve antimicrobial stewardship processes at VA hospitals that lack local ID support. Researchers aimed to (1) identify structural factors and processes associated with facility-level ASP performance, (2) determine provider attitudes and organizational factors that impede or foster antimicrobial stewardship at VA hospitals that lack ID support, and (3) conduct a pilot intervention to bolster antimicrobial stewardship at VA hospitals that have low-performing ASPs and lack local ID support.

Researchers sought to achieve their aims by:

• Evaluating antimicrobial prescribing across a large cohort of VA inpatients.
• Qualitatively assessing local barriers and facilitators to antimicrobial stewardship.
• Implementing and assessing a pilot intervention to augment local stewardship efforts.

Findings

• The primary responsibility for ASPs fell on the pharmacist champions.
• The pharmacist champions were more successful at gaining buy-in when they had established rapport with clinicians, but at some sites, the use of contract physicians and frequent staff turnover were potential barriers.
• Some sites felt that having access to an off-site ID specialist was important for overcoming institutional barriers and improving acceptance of their stewardship recommendations.
• In general, stewardship champions struggled to mobilize institutional resources, which made it difficult to advance their goals.

Expected implications

The findings of this research may inform the future implementation of ASPs in settings that lack ID expertise, and they set the stage for future investigations of evaluating and implementing stewardship processes in other healthcare settings, including ambulatory clinics, emergency rooms, and community living centers.

Principal investigator

Daniel J. Livorsi, MD, MS, is with HSR&D’s Center for Access & Delivery Research and Evaluation (CADRE) at the Iowa City VA Medical Center.

Publications

The work of Dr. Livorsi and his colleagues has resulted in the following recent publications:

Livorsi D, Drainoni M-L, Reisinger H, et al. Leveraging implementation science to advance antibiotic stewardship practice and research. Infection Control and Hospital Epidemiology. February 2022;43(2):139–146.

Livorsi D, Steffensmeier K, Perencevich E, et al. Antibiotic stewardship implementation at hospitals without on-site infectious disease specialists: A qualitative study. Infection Control & Hospital Epidemiology. May 2022;43(5):576–581.

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Diagnostic stewardship as a “nudge” to reduce inappropriate antibiotic use for urinary tract infections

Overuse of antibiotics is a leading cause of antibiotic-resistant bacteria, which are estimated by the Centers for Disease Control and Prevention to kill more than 23,000 Americans each year. A major factor in antibiotic overuse is inappropriate or unnecessary culturing, particularly unnecessary urine culturing that identifies colonization and leads to overdiagnosis of urinary tract infections (UTI). Researchers found significant reductions in unnecessary urine cultures and associated antibiotic use through diagnostic stewardship that modifies the ordering, processing, or reporting of a “positive” culture that generally should not be treated. Diagnostic stewardship is synergistic with antimicrobial stewardship as it improves the value and accuracy of urine testing before treatment.

About this study

Modifying how diagnostic tests are ordered, processed, or reported can help improve patient care by using existing technology more effectively—a “nudge” approach based in psychology and behavioral economics. This ongoing study (October 2020–September 2024) uses VA’s electronic medical record (EMR) to improve the appropriateness of test ordering and reporting within VA healthcare systems. To address gaps related to diagnostic stewardship, researchers have defined the best UTI diagnostic stewardship criteria, and developed implementation methods for UTI diagnostic stewardship, including an EMR interface and lab protocols. In the coming months, they will implement these changes in 3 VISNs to assess the benefits and any harms of real-life UTI diagnostic stewardship in acute care, long-term care, and ambulatory care.

Preliminary findings

• Compared to control sites, sites with diagnostic stewardship policies performed significantly fewer urine cultures.
• Immediately upon implementation, urine culture rates decreased in intervention sites relative to control sites, with minimal monthly trend changes.
• Conditional urine reflex testing policies in the acute-care setting were associated with reduced unnecessary urine culturing without adverse effects.

Expected implications

Diagnostic stewardship has the potential to limit inappropriate urine culturing and thereby reduce unnecessary antibiotic use for over-diagnosed UTI at a minimal cost and without adverse consequences. If successful, the approaches from this study could be readily implemented to reduce antimicrobial resistance across the VA healthcare system and other hospitals, reducing catheter-associated UTI and C. difficile rates, and improving the care and safety of Veterans.

Principal investigator

Daniel J. Morgan, MD, MS, is an HSR&D investigator and research mentor with the VA Maryland Healthcare System in Baltimore, MD.

Publications

The work of Dr. Morgan and his colleagues has been highlighted in the following recent publications:

Claeys K, Trautner B, Morgan D, et al. Optimal urine culture diagnostic stewardship practice. Clinical Infectious Diseases. August 31, 2022;75(3):382–389.

Claeys K, Zhan M, Morgan D, et al. Conditional reflex to urine culture: Evaluation of a diagnostic stewardship intervention within the VA and CDC practice-based research network. Infection Control & Hospital Epidemiology. February 2021;42(2):176–181.

Morgan D, Pineles L, Owczarzak J, et al. Accuracy of practitioner estimates of probability of diagnosis before and after testing. JAMA Internal Medicine. April 5, 2021;181(6):747–755.

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Development of a stewardship intervention for CLC pharmacists to improve UTI treatments

Studies suggest that up to 75% of the antibiotics used in long-term care facilities (LTCFs) are incorrectly prescribed, which likely contributes to the rapid growth of antibiotic-resistant bacteria in these communities. Additionally, the harms of antibiotic misuse in frail, older LTCF residents are significant and include Clostridium difficile infection, adverse drug events and drug interactions, and infection with resistant bacteria. Treatment of suspected urinary tract infection (UTI) is the largest contributor to antibiotic use in VA long-term care facilities (known as community living centers or CLCs), where antibiotic stewardship is largely absent.

About this study

The long-term goal of this research is to improve the quality of care of CLC residents nationally through reduction of inappropriate antibiotic use. Three specific aims include:

• Describe UTI-related antibiotic use and inappropriate antibiotic use among VA CLCs nationally and identify independent predictors of inappropriate antibiotic use.
• Develop an educational intervention that targets CLC pharmacists to reduce inappropriate treatment of UTIs and pilot test the intervention.
• Evaluate the effectiveness of the educational intervention on UTI-related antibiotic use and the frequency of inappropriate antibiotic use.

Findings

• Potentially suboptimal antibiotic treatment was identified in 65% of the more than 20,000 residents with an incident UTI treated in 120 VA CLCs.
• Predictors of suboptimal antibiotic treatment included prior fluoroquinolone exposure, chronic renal disease, age ≥85 years, prior skin infection, recent high white blood cell count, and genitourinary disorder.
• Potentially suboptimal UTI treatment was highly variable across VA CLCs.
• Potentially suboptimal antibiotic treatment was associated with a 5% increased risk of a composite measure of poor clinical outcome (defined as UTI recurrence), acute care hospitalization/emergency department visit, adverse drug event, Clostridioides difficile infection (CDI), or death within 30 days of antibiotic discontinuation, which was driven by a 68% increased risk of CDI.

Analysis of interviews with CLC staff members and development of interventions to reduce inappropriate antibiotic use in CLCs continues.

Implications

This research demonstrated that suboptimal antibiotic treatment of residents with UTIs in VA CLCs is common. Additionally, beyond the decision to use antibiotics, clinicians should consider the potential harms of suboptimal treatment choices for UTI regarding drug type, dose frequency, and duration. Interventions that can be disseminated broadly to improve antibiotic use and, ultimately, the quality of care for Veterans nationally through reduced inappropriate antibiotic use are still needed in VA CLCs.

Principal investigator

Haley Appaneal, PharmD, is with HSR&D’s Center of Innovation in Long-term Services and Supports in Providence, RI.

Publications

The work of Dr. Appaneal and her colleagues was highlighted recently in the following publications:

Appaneal H, Caffrey A, Lopes V, et al. Frequency and predictors of suboptimal prescribing among a cohort of older male residents with urinary tract infections. Clinical Infectious Diseases. November 1, 2021;73(9):e2763–e2772.

Appaneal H, Shireman T, Lopes V, et al. Poor clinical outcomes associated with suboptimal antibiotic treatment among older long-term care facility residents with urinary tract infection. BMC Geriatrics. July 23, 2021;21(1):436.

Appaneal H, Caffrey A, Lopes V, et al. Predictors of potentially suboptimal treatment of urinary tract infections in long-term care facilities. The Journal of Hospital Infection. April 1, 2021;110:114–121.

Sine K, Appaneal H, Dosa D, et al. Antimicrobial prescribing in the telehealth setting: Framework for stewardship during a period of rapid acceleration within primary care. Clinical Infectious Diseases. July 30, 2022; online ahead of print.

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Less is more: Improving antimicrobial stewardship for asymptomatic bacteriuria

Antibiotic and antimicrobial stewardship to combat the spread of antibiotic-resistant bacteria is a national priority, both within and outside VA. Stewardship includes reducing the inappropriate use of antimicrobials—antibiotics and agents that kill or inhibit bacteria, fungi, parasites, viruses, and more—for asymptomatic bacteriuria (ASB), a very common condition in which bacteria are present in urine samples from patients who have no signs or symptoms of a urinary tract infection. Despite evidence-based guidelines that recommend against culturing the urine to screen for and treat ASB with antimicrobials, ASB treatment frequently occurs.

An intervention to decrease guideline-discordant ordering of urine cultures and antibiotics for ASB, “Kicking Catheter Associated Urinary Tract Infection (Kicking CAUTI),” reduced unnecessary screening for ASB by 71% and unnecessary treatment of ASB by 75% in a large and complex VA medical center. Initiating antimicrobial therapy only for ASB patients who will benefit from treatment will enhance patient safety and combat microbial resistance.

An evaluation recently conducted by the VA Antimicrobial Stewardship Task Force shows an acute need for further CAUTI intervention, as 57% of 1,219 urine cultures treated as urinary tract infection (with antibiotics) were, in fact, ASB.

About this study

This study sought to facilitate implementation of a scalable version of Kicking CAUTI and assess what aspects of an antimicrobial stewardship intervention are essential to success and sustainability in reducing unnecessary urine culture orders and antibiotic use for ASB.

Investigators compared four geographically diverse intervention sites with four comparison sites from October 2017 through April 2020. The intervention was delivered at a distance and included case-based teaching on how to apply an evidence-based algorithm to distinguish urinary tract infection from ASB. A central coordinating center provided external facilitation (e.g., organizing monthly meetings for the four local site teams), while a local champion at each intervention site served as an internal facilitator. Veterans in this study (n = 11,299) included those admitted to a VA acute care medicine ward or residing in a VA community living center long-term care unit during the study period. Outcomes were the total number of urine cultures ordered by inpatient or long-term care providers and antimicrobial use.

The intervention was directed at providers in acute and long-term care with a goal of reducing inappropriate screening for and treatment of ASB in all patients and residents.

Findings

• The antibiotic stewardship intervention was associated with significantly fewer urine cultures ordered and fewer days of antibiotic therapy, translating over the course of the research to 2,881 fewer urine cultures, 8,193 fewer days of unnecessary antibiotic therapy, and 6,393 more days without antibiotics across the four VA sites.
• There was a significant increase in urine cultures and days of antibiotic therapy in the comparison sites.

Implications

Findings suggest that antibiotic stewardship for ASB can be implemented effectively at multiple sites from a distance via a mix of external and internal facilitation, resulting in a decrease in urine cultures and antibiotic use. Further dissemination to VA facilities in collaboration with the VA Antimicrobial Stewardship Task Force is planned.

Principal investigator

Barbara Wells Trautner, MD, PhD, is part of HSR&D’s Center for Innovations in Quality, Effectiveness, and Safety (IQuEST) at the Michael E. DeBakey VA Medical Center in Houston, TX.

Publications

This study was included in the following recent publications:

Grigoryan L, Naik A, Lichtenberger P, and Trautner B, et al. Analysis of an antibiotic stewardship program for asymptomatic bacteriuria in the VA Healthcare System. JAMA Network Open. July 25, 2022;5(7):e2222530.

Valentine-King M, Van J, Trautner, B, et al. Identification of novel factors associated with inappropriate treatment of asymptomatic bacteriuria in acute and long-term care. American Journal of Infection Control. February 11, 2022; online ahead of print.

Dr. Trautner was featured in an HSR&D video.

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