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Antimicrobial stewardship reduces C. difficile prevalence, drug resistance
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Cutting back on the use of 4C antibiotics reduced total Clostridium difficile infections and was predictive of declines in multidrug-resistant ribotypes, researchers in Scotland found.
“Quasi-experimental studies from the UK have linked subsequent declines in C. difficile infection incidence and mortality to improved infection prevention and control and antibiotic stewardship,” Timothy Lawes, BSc, MBBS, MSc, MRCPCH, of the department of pediatrics, Royal Aberdeen Children’s Hospital, Aberdeen, Scotland, and colleagues wrote. “However, most of these studies have focused on single hospitals over a short time and inconsistently controlled for expected trends, population interactions, or concurrent interventions. As with other antibiotic-resistant pathogens, selective advantage of multidrug-resistant epidemic strains might depend on a critical level of antibiotic selection pressure, or ‘total use threshold.’ Declines in C. difficile infection in the U.K. have coincided with shifts in ribotype distribution, but whether these declines are spontaneous or result from interventions is unclear.”
Lawes and colleagues performed a non-linear time-series analysis and quasi-experimental study using a Scottish health board that served 11% of the country’s total population. The researchers imposed a mixed persuasive-restrictive 4C antibiotic stewardship program on May 1, 2009, reviewing C. difficile cases that occurred between Jan. 1, 1997 and Dec. 31, 2012.
The researchers identified 4,885 cases of hospital-onset C. difficile infection, and 1,625 community-onset cases. Care centers reduced 4C antibiotic use by 50% during the study period both in hospitals (mean reduction, 193 daily doses per 1,000 occupied bed-days; 95% CI, 45-328) and the community (mean reduction, 1.85 daily doses per 1,000 inhabitant-days, 95% CI, 0.23-3.48). Vector models showed that declining 4C antibiotic use was associated with a “rapid decline” in the incidence of C. difficile ribotypes R001 and R027, Lawes and colleagues wrote.
During antibiotic stewardship, hospital-onset infection prevalence density fell by 68% compared to predictions without intervention (mean reduction, 1.01 cases per 1,000 occupied bed-days, 95% CI, 0.27-1.76), while community-onset infection prevalence density fell by 45% (mean reduction, 0.083 cases per 100,000 inhabitant-days, 0.045-0.121), the researchers reported. Lawes and colleagues estimated that by December 2012, the antibiotic stewardship program prevented 524 community-onset C. difficile infections and 1,370 hospital-onset infections.
“Overall, we found that an antibiotic stewardship strategy limiting use of 4C antibiotics predicted rapid declines in C. difficile infection rates in hospital and community populations,” Lawes and colleagues wrote. “Reducing consumption of these drugs to below population-specific total use thresholds might remove the antibiotic selection pressures favoring epidemic multidrug-resistant ribotypes.”
“Confounders are not completely accounted for and thus conclusions should always be carefully drawn,” Christopher J. Graber, MD, MPH, of the infectious diseases section of the VA Greater Los Angeles Healthcare System and David Geffen School of Medicine at the University of California, Los Angeles, wrote in an accompanying editorial.
“Nevertheless, the authors should be congratulated for showing not only that their systematic efforts substantially and sustainably changed provider prescribing behavior but also that this intermediate process measure was strongly associated with reductions in population-level rates of C. difficile infection. The strong evidence of the clinical benefits of wide-scale antimicrobial stewardship interventions should give encouragement for those of us in the antimicrobial stewardship community who continually strive to similarly design and implement large-scale efforts to change provider behavior.” – by Andy Polhamus
Disclosure: Graber and Lawes report no relevant financial disclosures. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.
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