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Management Brief No. 74

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Management eBriefs
Issue 74December 2013

A Systematic Review: Antimicrobial Stewardship Programs

It is estimated that in 2009, more than 3 million kilograms of antimicrobials were administered to patients in the United States. While the life-saving benefits of antimicrobials are clear, the major concerns related to their use are increasing resistance, higher incidence of Clostridium difficile infection (CDI), and increased healthcare costs (i.e., related to adverse events). There also is evidence of adverse outcomes associated with inadequate antimicrobial therapy. An antimicrobial stewardship program (ASP) is a focused effort by a healthcare system, hospital, or portion of a hospital (e.g., an intensive care unit) to optimize the use of antimicrobial agents in order to improve patient outcomes, reduce adverse effects (e.g., rash, drug fever, hepatitis, renal dysfunction), reduce antimicrobial resistance, and deliver cost-effective therapy.

Investigators with the VA Evidence-based Synthesis Program in Minneapolis conducted a synthesis of the evidence about the effectiveness of ASPs implemented in hospital settings. The topic was nominated on behalf of the VA Antimicrobial Stewardship Task Force, in order to help guide clinical practice and policy in regard to inpatient ASPs within the VA Healthcare System. Investigators reviewed more than 6,000 titles and abstracts published between 2000 and June 2013 and identified 35 studies, including 9 randomized controlled trials (RCTs); in addition, three systematic reviews relevant to the topic were examined.

Summary of review results:
There is low-quality evidence that antimicrobial stewardship programs can improve prescribing and microbial outcomes, with reduced costs and without significant adverse impact on patient outcomes. However, the authors caution against over-interpretation of findings due to variability in study design, poor generalizability, potential selective reporting bias, and a dearth of high-quality evidence. The full report contains a synthesis of the literature on stewardship and implementation science to provide a tentative roadmap for hospitals until better evidence is available.

Please see more detailed findings in regard to the following five key Questions.

Question #1
What is the effectiveness of inpatient ASPs on: 1) Patient-centered outcomes, including 30-day readmission, mortality, CDI, length of stay, and adverse effects; and 2) Secondary outcomes, such as antimicrobial prescribing, microbial outcomes, and costs?

Patient-Centered Outcomes

  • A systematic review of studies published through 2009 reported that:
    • Interventions to increase effective prescribing in patients with any infection had no effect on mortality (3 studies), whereas interventions to increase guideline compliance in patients with community-acquired pneumonia were associated with reduced mortality (4 studies).
    • Interventions to decrease excessive prescribing had no effect on mortality (11 studies) or length of hospital stay (6 studies).
    • In five studies reporting on CDI, the median effect was a 68% reduction in infection.
  • The recent literature (i.e., 35 studies not included in a previous systematic review) generally supports the findings of the systematic review.
    • There was low strength of evidence that ASPs involving audit and feedback, formulary restriction and pre-authorization, guidelines or protocols, or computerized decision support had no significant negative impact on mortality, hospital stay, or 30-day readmission.
    • Incidence of CDI (6 studies) was decreased or unchanged.

Secondary Outcomes

  • A systematic review of studies published through 2009 reported that:
    • Interventions were associated with improved prescribing outcomes based on median outcome effect sizes (i.e., the percent of patients with an improvement or change in the antimicrobial selection, dose, route, or duration versus control patients). Also, interventions were typically associated with effect-size changes in microbial outcomes in the direction of the intended effect.
    • Intervention costs and financial savings were reported in 10 studies. In eight of the studies, savings were greater than costs.
  • In the recent literature:
    • ASPs were associated with decreased use and/or increased appropriate use of antimicrobials. Fewer studies reported on antimicrobial selection, timing, or duration of use, but results generally favored ASPs.
    • Nine studies reported microbial outcomes, with most reporting improvements associated with ASPs.
    • Fourteen studies reported decreased drug costs.

Question #2
What are the key intervention components associated with effective inpatient antimicrobial stewardship (e.g., persuasive, restrictive, structural, or combination intervention; personnel mix; level of support)?

  • Consistent and persistent effort from qualified personnel employing effective communication skills, and often supported by electronic medical records or computerized decision support systems were central themes through the six studies that addressed this question.
  • One study noted that a computerized clinical decision support system was time saving compared with manual chart review and recommendations.

Question #3
Does effectiveness vary by hospital setting (e.g., rural, urban, academic, VA, non-VA), or by suspected patient condition?

  • None of the studies in this review were conducted at VAMCs. Nearly all studies were conducted in university-affiliated teaching hospitals. Only six studies were conducted in community hospitals, and nine in ICUs.
  • Many studies had different focuses, making it difficult to reach any conclusions about differences in effectiveness according to hospital setting or unit (ICU or other unit). Also, because intervention components, study design, patient populations, and targeted infection or antimicrobial use differed across studies, investigators caution against inferring that any outcome variation was due to hospital setting or unit.
  • Lung infections were the most frequently reported specific patient condition (seven studies). However, due to limited information and variability in study design, intervention, and patient characteristics, investigators urge caution in trying to assess whether effectiveness varies by suspected patient condition.

Question #4
What are the harms of inpatient antimicrobial stewardship programs?

  • Only two studies reported possible harms associated with implementation of antimicrobial stewardship programs. In both studies, the reporting of harms was anecdotal.
  • Other "harms" could include statistically significant adverse increases in patient, microbial, or prescribing outcomes due to the ASP intervention. However, reports of possible harms were rare and the evidence was of low quality.

Question #5
Within the included studies, what are the barriers to implementation, sustainability, and scalability of inpatient antimicrobial stewardship programs?

  • Four studies described implementation barriers. Based on a single survey, barriers to adherence were identified as knowledge, attitude, and external barriers.
  • Suggestions to improve implementation included: gaining a better understanding of the local prescribing culture, fostering an environment of appropriate prescribing, and increasing collaboration between physicians specializing in infectious diseases and pharmacists.
  • Most studies were conducted over one year or less and did not comment on sustainability.
  • No studies commented on scalability.

Future Research
Future research is sorely needed to clarify the benefits, potential harms, barriers, sustainability, and costs of antimicrobial stewardship programs. Generous funding for comparative effectiveness trials would be ideal. Units within large healthcare organizations are likely conducting one or more stewardship activities. These organizations should strongly consider organizing these activities in a way that provides useful information on comparative effectiveness. Healthcare payers also should recognize that large amounts of money will be spent on antimicrobial stewardship, and that these expenditures can be more efficiently utilized if comparative research is done to identify the most effective approaches and strategies. Given that it may be hard to avoid cross-over or contamination in studies randomized at the subject level, cluster RCTs may be the most feasible way to provide high-quality evidence. Large healthcare organizations could play a role since they could provide the multiple sites--and shared data--that would make such a study feasible.

A cyberseminar session on this ESP Report was held on December 16, 2013. Go to the HSR&D Cyberseminar Archives web page to view this session.

This report is a product of VA/HSR&D's Quality Enhancement Research Initiative's (QUERI) Evidence-Based Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers — and to disseminate these reports throughout VA.


Filice G, Drekonja D, Greer N, Butler M, Wagner B, MacDonald R, Carlyle M, Rutks I, Wilt T. Antimicrobial Stewardship Programs in Inpatient Settings: A Systematic Review. VA-ESP Project #09-009; 2013.

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This Management eBrief is a product of the HSR&D Evidence Synthesis Program (ESP). ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.

This Management e-Brief is provided to inform you about recent HSR&D findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR&D Resource Center charged with disseminating important HSR&D findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of the HSR&D Evidence-Based Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers - and to disseminate these reports throughout VA.

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