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Antibiotic Exposure and Risk for Hospital-Associated Clostridioides difficile Infection.

ABSTRACT: Clostridioides difficile infection (CDI) is a health care-associated infection associated with significant morbidity and cost, with highly varied risk across populations. More effective, risk-based prevention strategies are needed. Here, we investigate risk factors for hospital-associated CDI in a large integrated health system. In a retrospective cohort of all adult admissions to 21 Intermountain Healthcare hospitals from 2006 to 2012, we identified all symptomatic (i) hospital-onset and (ii) health care-facility-associated, community-onset CDI. We then evaluated the risk associated with antibiotic exposure, including that of specific agents, using multivariable logistic regression. A total of 2,356 cases of CDI among 506,068 admissions were identified (incidence, 46.6 per 10,000). Prior antibiotic use was the dominant risk factor, where for every antibiotic day of therapy prior to the index admission, the odds of subsequent CDI increased by 12.8% (95% confidence interval [CI], 12.2 to 13.4%; P < 0.0001). This was a much stronger association than was inpatient antibiotic exposure (odds ratio [OR], 1.007 [95% CI, 1.005 to 1.009]; P < 0.0001). The highest-risk antibiotics included second-generation and later cephalosporins (especially oral), carbapenems, fluoroquinolones, and clindamycin, while doxycycline and daptomycin were associated with a lower CDI risk. We concluded that cumulative antibiotic exposure prior to admission is the greatest contributor to the risk of subsequent CDI. Most classes of antibiotics carry some risk, which varies by drug and route. This information may be useful for antimicrobial stewardship efforts.

SUBMITTER: Webb BJ

PROVIDER: S-EPMC7179314 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Antibiotic Exposure and Risk for Hospital-Associated Clostridioides difficile Infection.

Webb Brandon J BJ Subramanian Aruna A Lopansri Bert B Goodman Bruce B Jones Peter Bjorn PB Ferraro Jeffrey J Stenehjem Edward E Brown Samuel M SM

Antimicrobial agents and chemotherapy 20200324 4

<i>Clostridioides difficile</i> infection (CDI) is a health care-associated infection associated with significant morbidity and cost, with highly varied risk across populations. More effective, risk-based prevention strategies are needed. Here, we investigate risk factors for hospital-associated CDI in a large integrated health system. In a retrospective cohort of all adult admissions to 21 Intermountain Healthcare hospitals from 2006 to 2012, we identified all symptomatic (i) hospital-onset and ...[more]

PMID: 31964789

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Project description:ImportanceRegulatory agencies and professional organizations recommend antibiotic stewardship programs (ASPs) in US hospitals. The optimal approach to establish robust, sustainable ASPs across diverse hospitals is unknown.ObjectiveTo assess whether the Agency for Healthcare Research and Quality Safety Program for Improving Antibiotic Use is associated with reductions in antibiotic use across US hospitals.Design, setting, and participantsA pragmatic quality improvement program was conducted and evaluated over a 1-year period in US hospitals. A total of 437 hospitals were enrolled. The study was conducted from December 1, 2017, to November 30, 2018. Data analysis was performed from March 1 to October 31, 2019.InterventionsThe Safety Program assisted hospitals with establishing ASPs and worked with frontline clinicians to improve their antibiotic decision-making. All clinical staff (eg, clinicians, pharmacists, and nurses) were encouraged to participate. Seventeen webinars occurred over 12 months, accompanied by additional durable educational content. Topics focused on establishing ASPs, the science of safety, improving teamwork and communication, and best practices for the diagnosis and management of infectious processes.Main outcomes and measuresThe primary outcome was overall antibiotic use (days of antibiotic therapy [DOT] per 1000 patient days [PD]) comparing the beginning (January-February 2018) and end (November-December 2018) of the Safety Program. Data analysis occurred using linear mixed models with random hospital unit effects. Antibiotic use from 614 hospitals in the Premier Healthcare Database from the same period was analyzed to evaluate contemporary US antibiotic trends. Quarterly hospital-onset Clostridioides difficile laboratory-identified events per 10 000 PD were a secondary outcome.ResultsOf the 437 hospitals enrolled, 402 (92%) remained in the program until its completion, including 28 (7%) academic medical centers, 122 (30%) midlevel teaching hospitals, 167 (42%) community hospitals, and 85 (21%) critical access hospitals. Adherence to key components of ASPs (ie, interventions before and after prescription of antibiotics, availability of local antibiotic guidelines, ASP leads with dedicated salary support, and quarterly reporting of antibiotic use) improved from 8% to 74% over the 1-year period (P < .01). Antibiotic use decreased by 30.3 DOT per 1000 PD (95% CI, -52.6 to -8.0 DOT; P = .008). Similar changes in antibiotic use were not observed in the Premier Healthcare Database. The incidence rate of hospital-onset C difficile laboratory-identified events decreased by 19.5% (95% CI, -33.5% to -2.4%; P = .03).Conclusions and relevanceThe Agency for Healthcare Research and Quality Safety Program appeared to enable diverse hospitals to establish ASPs and teach frontline clinicians to self-steward their antibiotic use. Safety Program content is publicly available.

Project description:The gut bacterial community prevents many pathogens from colonizing the intestine. Previous studies have associated specific bacteria with clearing Clostridioides difficile colonization across different community perturbations. However, those bacteria alone have been unable to clear C. difficile colonization. To elucidate the changes necessary to clear colonization, we compared differences in bacterial abundance between communities able and unable to clear C. difficile colonization. We treated mice with titrated doses of antibiotics prior to C. difficile challenge, resulting in no colonization, colonization and clearance, or persistent colonization. Previously, we observed that clindamycin-treated mice were susceptible to colonization but spontaneously cleared C. difficile Therefore, we investigated whether other antibiotics would show the same result. We found that reduced doses of cefoperazone and streptomycin permitted colonization and clearance of C. difficile Mice that cleared colonization had antibiotic-specific community changes and predicted interactions with C. difficile Clindamycin treatment led to a bloom in populations related to Enterobacteriaceae Clearance of C. difficile was concurrent with the reduction of those blooming populations and the restoration of community members related to the Porphyromonadaceae and Bacteroides Cefoperazone created a susceptible community characterized by drastic reductions in the community diversity and interactions and a sustained increase in the abundance of many facultative anaerobes. Lastly, clearance in streptomycin-treated mice was associated with the recovery of multiple members of the Porphyromonadaceae, with little overlap in the specific Porphyromonadaceae observed in the clindamycin treatment. Further elucidation of how C. difficile colonization is cleared from different gut bacterial communities will improve C. difficile infection treatments.IMPORTANCE The community of microorganisms, or microbiota, in our intestines prevents pathogens like C. difficile from colonizing and causing infection. However, antibiotics can disturb the gut microbiota, which allows C. difficile to colonize. C. difficile infections (CDI) are primarily treated with antibiotics, which frequently leads to recurrent infections because the microbiota has not yet returned to a resistant state. The recurrent infection cycle often ends when the fecal microbiota from a presumed resistant person is transplanted into the susceptible person. Although this treatment is highly effective, we do not understand the mechanism. We hope to improve the treatment of CDI through elucidating how the bacterial community eliminates CDI. We found that C. difficile colonized susceptible mice but was spontaneously eliminated in an antibiotic treatment-specific manner. These data indicate that each community had different requirements for clearing colonization. Understanding how different communities clear colonization will reveal targets to improve CDI treatments.

Dataset Information

Antibiotic Exposure and Risk for Hospital-Associated Clostridioides difficile Infection.

Publications

Antibiotic Exposure and Risk for Hospital-Associated Clostridioides difficile Infection.

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