July 2014 - Duke Antimicrobial Stewardship Outreach Network

DUKE ANTIMICROBIAL STEWARDSHIP OUTREACH NETWORK (DASON)
Antimicrobial Stewardship News
Volume 2, Number 7, July 2014
Reduce Clostridium difficile Risk with Antimicrobial Stewardship
Background
Clostridium difficile infection (CDI) occurs in more than 300,000 hospitalized patients in the United
States each year (1). Hospitalizations for patients with CDI cost an average $24,000, and the annual
aggregate inpatient costs exceed $8 billion. Furthermore, approximately 10% of hospitalized patients
with CDI die prior to hospital discharge.
Antimicrobial stewardship programs (ASPs) promote improved patient outcomes by helping patients to
receive the most appropriate antibiotics for the correct duration (2). A primary goal of ASPs is to
decrease infections with multi-drug resistant organisms by limiting unnecessary antibiotic use,
particularly with broad-spectrum antibiotics. Antibiotic exposure is also the fundamental risk factor for
CDI (3). Therefore, perhaps not surprisingly, several observational studies have suggested a decrease in
the incidence of CDI at hospitals after implementation of ASPs.
This newsletter reviews a recently published meta-analysis that analyzed previously published studies to
determine the effect of antimicrobial stewardship programs on CDI incidence (4).
Antimicrobial Stewardship Programs and C. difficile Incidence: the Meta-Analysis
Study design
The meta-analysis written by Feazel et al. included 16 studies and analyzed CDI rates from more than
400,000 total patients at hospitals that employed antimicrobial stewardship programs. Some ASPs
utilized “restrictive” stewardship interventions, while other programs used “persuasive” interventions.
Restrictive techniques included requiring prior approval from the stewardship team to prescribe
selected antibiotics or completely removing certain antibiotics from the hospital formulary. Persuasive
techniques attempted to change prescriber behavior without active restriction, such as through
education, changes in suggested hospital protocols, and post-prescription review with
recommendations from the stewardship team. Of the 16 ASPs analyzed in the meta-analysis, eight used
restrictive stewardship policies, and five used persuasive techniques; the methods of the other three
studies were unclear. Fourteen of the 16 ASPS targeted cephalosporin use, and six programs targeted
unnecessary fluoroquinolone administration.
Study results
 Implementation of ASPs showed significant overall benefit, decreasing risk of infection with C.
difficile by 52%.
 ASPs that operated on the hospital-wide level were beneficial. ASPs that specifically targeted
geriatric wards, where CDI is most common, were also beneficial.
 Restrictive (prior approval, removal from pharmacy) and persuasive (post-prescription review) ASP
techniques decreased CDI risk.
 Decreasing unnecessary use of cephalosporins or fluoroquinolones were successful strategies for
reducing the risk of CDI.
 ASP interventions significantly decreased CDI risk less than 9 months after implementation in some
hospitals. The longer the ASP was operational, the greater the reduction in risk of CDI.
Study limitations
Nearly all studies had quasi-experimental interrupted time series or before-after designs; no randomized
controlled trials on this topic were available. Therefore, the average quality of the included studies was
characterized as low. The meta-analysis would be stronger if it included higher quality studies, such as a
randomized controlled trial, but these studies have not been performed. Also, six of the studies were
published in 2002 or earlier, so the generalizability to current C. difficile strains and hospitals is unclear.
Finally, most of the ASPs were implemented in the United Kingdom; only two of the 16 studies took
place in the US.
Conclusions
Antimicrobial stewardship programs can successfully decrease the risk of Clostridium difficile infection in
hospitalized patients. Both restrictive and persuasive techniques have been effective in decreasing CDI
risk by limiting unnecessary use of cephalosporins and fluoroquinolones. Though the studies included in
the meta-analysis mainly focused on these two groups of antibiotics, we expect that reducing
unnecessary use of other broad-spectrum antibiotics such as carbapenems (e.g., meropenem,
imipenem, ertapenem) would also decrease C. difficile risk. Furthermore, we believe that CDI risk can be
impacted by decreasing the use of any antibiotic.
DASON physicians and pharmacists can assess the antimicrobial stewardship needs at your hospital,
based on local epidemiology and antibiotic resistance, prescribing patterns, and hospital resources. We
can help design appropriate restrictive or persuasive stewardship initiatives to promote better patient
care, fewer infections with multi-drug resistant organisms, and decreased risk of Clostridium difficile
infection.
References
1.
2.
3.
4.
Lucado J, Gould C, Elixhauser A. Clostridium Difficile Infections (CDI) in Hospital Stays, 2009:
Statistical Brief #124. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville
(MD), 2012.
Antibiotic stewardship - the ultimate return on investment. Centers for Disease Control and
Prevention website. http://www.cdc.gov/getsmart/healthcare/factsheets/antibiotic-use.html.
Accessed June 21, 2014.
Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in
epidemiology and pathogenesis. Nature reviews Microbiology 2009;7:526-36.
Feazel LM, Malhotra A, Perencevich EN, Kaboli P, Diekema DJ, Schweizer ML. Effect of antibiotic
stewardship programmes on Clostridium difficile incidence: a systematic review and metaanalysis. The Journal of antimicrobial chemotherapy 2014;69:1748-1754.

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