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Current evidence on hospital antimicrobial stewardship objectives: a systematic review and meta-analysis

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Summary

Background

Antimicrobial stewardship is advocated to improve the quality of antimicrobial use. We did a systematic review and meta-analysis to assess whether antimicrobial stewardship objectives had any effects in hospitals and long-term care facilities on four predefined patients' outcomes: clinical outcomes, adverse events, costs, and bacterial resistance rates.

Methods

We identified 14 stewardship objectives and did a separate systematic search for articles relating to each one in Embase, Ovid MEDLINE, and PubMed. Studies were included if they reported data on any of the four predefined outcomes in patients in whom the specific antimicrobial stewardship objective was assessed and compared the findings in patients in whom the objective was or was not met. We used a random-effects model to calculate relative risk reductions with relative risks and 95% CIs.

Findings

We identified 145 unique studies with data on nine stewardship objectives. Overall, the quality of evidence was generally low and heterogeneity between studies was mostly moderate to high. For the objectives empirical therapy according to guidelines, de-escalation of therapy, switch from intravenous to oral treatment, therapeutic drug monitoring, use of a list of restricted antibiotics, and bedside consultation the overall evidence showed significant benefits for one or more of the four outcomes. Guideline-adherent empirical therapy was associated with a relative risk reduction for mortality of 35% (relative risk 0·65, 95% CI 0·54–0·80, p<0·0001) and for de-escalation of 56% (0·44, 0·30–0·66, p<0·0001). Evidence of effects was less clear for adjusting therapy according to renal function, discontinuing therapy based on lack of clinical or microbiological evidence of infection, and having a local antibiotic guide. We found no reports for the remaining five stewardship objectives or for long-term care facilities.

Interpretation

Our findings of beneficial effects on outcomes with nine antimicrobial stewardship objectives suggest they can guide stewardship teams in their efforts to improve the quality of antibiotic use in hospitals.

Funding

Dutch Working Party on Antibiotic Policy and Netherlands National Institute for Public Health and the Environment.

Introduction

Although the benefits of antibiotic use are indisputable, misuse and overuse of antibiotics have contributed to antibiotic resistance, which has become a serious and growing threat to public health.1, 2 Patients with infections caused by resistant bacteria generally have an increased risk of poor clinical outcomes and death and use more health-care resources than patients infected with non-resistant bacteria of the same species.2

Of all antibiotics prescribed in acute-care hospitals, 20–50% are either unnecessary or inappropriate.3, 4, 5, 6 Hospitals worldwide have been incorporating antimicrobial stewardship into hospital policy, with the goal of improving the quality of antimicrobial use. The primary goal of antimicrobial stewardship is to achieve optimum clinical outcomes and ensure cost-effectiveness of therapy while keeping to a minimum unintended consequences of antimicrobial use, including toxic effects, selection of pathogenic organisms, and the emergence of resistance.7 The characteristics of antimicrobial stewardship programmes vary8 but generally consist of a range of interventions that can be selected and adapted to fit the infrastructure of any hospital.9

In stewardship programmes, two sets of interventions should be distinguished. The first relates to recommended care at the patient level (stewardship objectives), such as treating patients according to the guidelines or taking cultures of blood and from the site of infection. The second set relates to recommended strategies for achieving the stewardship objectives, such as restrictive (eg, formulary restriction) and persuasive (eg, education and feedback) strategies, to improve appropriate antimicrobial use. The evidence for the second set of interventions has been systematically reviewed,5 but the yields of individual stewardship objectives do not seem to have been assessed.

We did a systematic review and meta-analysis to summarise the current state of evidence of the effects of antimicrobial stewardship objectives on patients' clinical outcomes (eg, mortality and length of stay [LOS] in hospital), adverse events, costs, and bacterial resistance rates in hospitals and long-term care facilities.

Research in context

Evidence before this study

We searched for all relevant studies published up to April 11, 2014, in Embase, Ovid MEDLINE, and PubMed. Each search addressed one of 14 antimicrobial stewardship objectives, and every search included terms for four predefined outcomes (clinical outcome, adverse events, costs, and resistance). An initial broad search strategy was used as the basis for all searches, to which specified strings were added that defined the 14 objectives being reviewed. Eligible study types were randomised controlled trials, non-randomised controlled trials, interrupted time series, and observational studies published in English, German, Spanish, French, or Dutch. We have found no systematic reviews published on this topic since our search.

Added value of this study

This systematic review revealed that the use of empirical therapy according to guidelines, de-escalation of therapy, switching from intravenous to oral treatment, therapeutic drug monitoring, use of a list of restricted antibiotics, and bedside consultation (especially in case of Staphylococcus aureus bacteraemia) are the most important objectives of the antimicrobial stewardship programme. The overall evidence for these objectives shows significant benefits for clinical outcomes, adverse events, costs, resistance rates, or combinations of these. However, the included studies were generally of low quality.

Implications of all the available evidence

For several antimicrobial stewardship objectives there is abundant, although low-quality, evidence on clinical outcomes, adverse events, costs, and resistance rates in hospitals. High-quality studies are now needed to provide better information on the effects of these objectives. We found no studies done in long-term care facilities, and research is needed in this setting. Our results combined with the previous critical appraisal of restrictive and persuasive strategies to improve appropriate antimicrobial use in patient care could guide hospital stewardship teams in improving the quality of antibiotic use.

Section snippets

Review topics

International experts had previously used a RAND-modified Delphi procedure to create a set of 11 quality indicators for appropriateness of antibiotic use in the treatment of all bacterial infections in adults while in hospital.10 Because these quality indicators were designed to be used in antimicrobial stewardship programmes to determine features of antibiotic use that need improvement, we used them as our set of stewardship objectives to study. Three additional objectives were mentioned in

Search results

In 14 searches we found 22 017 citations: 8330 in MEDLINE, 13 129 in Embase, and 558 in PubMed only. In addition to the primary search, we identified 87 papers by reviewing reference lists. After removing all duplicates, 16 387 papers remained. After screening of titles and abstracts, 669 potentially relevant studies were selected for full-text screening, including nine systematic reviews that were used to identify additional eligible studies. 146 papers (145 studies) met the inclusion criteria

Discussion

Our systematic review revealed that use of empirical therapy according to guidelines, de-escalation of therapy, switch from intravenous to oral therapy, therapeutic drug monitoring, use of a list of restricted antibiotics, and bedside consultation (especially for S aureus bacteraemia) can lead to significant benefits for clinical outcomes, adverse events, and costs, although the quality of evidence is generally low. Treatment according to guidelines and de-escalation of therapy had significant

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