Hospital antimicrobial stewardship programs (ASPs) may lower use of the drugs by almost 20%—nearly 40% in the intensive care unit (ICU)—and they were tied to a slight drop in infection rates, according to a meta-analysis last week in Antimicrobial Agents and Chemotherapy.
One third of hospitalized people and more than two thirds of ICU patients are receiving antimicrobial treatment at any given time, the authors said. The Centers for Disease Control and Prevention (CDC) estimates that up to half of all antibiotic use is inappropriate or unnecessary, contributing to 2 million infections and 23,000 deaths from drug-resistant bacteria each year.
Because hospital ASPs can vary widely in terms of goals, locally specific infection rates, and implementation methods, researchers from the Warren Alpert Medical School of Brown University and the Dana-Farber Cancer Institute conducted a meta-analysis of 26 studies that compared antibiotic use, measured in defined daily doses per 1,000 patient-days, and clinical outcomes before and after ASP implementation. Study periods ranged from 6 months to 3 years.
"Given the decrease in new antimicrobial agents and the imminent emergence of resistance shortly after the introduction of new agents, the CDC, the WHO [World Health Organization] and the US government have advocated that universal implementation of ASPs in hospitals, as a promising strategy to preserve antimicrobial benefit," the authors said.
Lower antimicrobial use across the board
After the implementation of an ASP, hospital antimicrobial consumption across all studies declined by 19.1%, and antibiotic costs fell by 33.9%. Though a modest decrease of 12.1% in antimicrobial use occurred in general medical wards, antimicrobial use in ICUs fell by 39.5% across the four studies that looked at that parameter, a decrease attributable to regularly high consumption of antimicrobial use and likelihood of an ASP having a larger effect in the critical care setting, the authors said.
Six studies that evaluated non-antibiotic therapies found that antifungal prescription rates declined by 39.1% after ASP initiation, even though only one hospital had explicitly restricted antifungals as part of the program, the authors said.
Nine studies analyzed the effect of ASPs that restricted "last-resort" antibiotics, including third- and fourth-generation cephalosporins, vancomycin, tigecycline, linezolid, imipenem, meropenem, and fluoroquinolones. Use of restricted agents fell by 26.6% after an ASP was implemented, and consumption of broad-spectrum antibiotics declined by 18.5%, the authors said.
Consumption of glycopeptides, including vancomycin, decreased by 14.7%, and carbapenem use for multidrug-resistant infections fell by 18.5%. Glycopeptide and carbapenem treatment rates fell significantly only in situations in which they had not previously been restricted or subject to prescription pre-authorization, the authors said.
Studies demonstrated no evidence for the "squeezing the balloon" phenomenon, "a term that is used to describe the concern that restricting some antimicrobial agents might lead to an increase in the non-restricted antimicrobials," the authors said. Instead, results supported the expectation that ASPs will provide dual benefits: a reduction in overall antibiotic use and better, evidence-based choices for drug therapy.
"ASPs seem to be effective not only because they result in a decrease in the quantity of antimicrobial consumption, but also positively affect antimicrobial choices," the authors said.
Lower risk of drug-resistant infections
Bacterial infection rates decreased by 4.5% across seven studies that measured clinical outcomes, and hospital length of stay fell by 8.9% across four studies, the authors said.
Length of ICU stay did not change significantly after an ASP was implemented, though it decreased by 1.5%, and no adverse effects attributed to drug stewardship in critical care environments occurred.
Hospital ASPs were associated with a significantly lower risk for infections caused by methicillin-resistant Staphylococcus aureus by 1.7%, imipenem-resistant Pseudomonas aeruginosa by 7.9%, and extensive-spectrum beta-lactamase Klebsiella species by 10.4%, the authors said. All studies involving infection risk with resistant bacteria evaluated the ASP for at least 1 year.
ASPs did not significantly lower the risk for Escherichia coli infections and were not associated with declining risks for Clostridium difficile (C diff) infections. Among the three studies that evaluated C diff rates, however, significant publication bias favored studies that reported ASPs' negative effects, the authors said.
Stewardship programs did not significantly change overall or infection-related 30-day mortality rates, which fell by 0.1% and 0.5%, respectively.
Regardless of variability in program implementation between hospitals, stewardship efforts resulted in lower antibiotic use, drug expenditures, infection rates, and length of hospitalization, the authors said.
They added, "Future studies should focus on the sustainability of these outcomes and evaluate potential beneficial long-term effects of ASPs in mortality and infection rates."
May 31 Antimicrob Agents Chemother study