Facility-level rates of hospital-onset Clostridioides difficile (formerly Clostridium difficile) infection (CDI) have been found to decrease correspondingly with lower usage of antibiotics, specifically third- and fourth-generation cephalosporins, and fluoroquinolones, according to a study published in Clinical Infectious Diseases.

This ecologic analysis included data from 549 acute-care hospitals from between 2006 and 2012. Hospital-onset C difficile was defined by a secondary CDI diagnosis on the ICD-9-CM diagnosis code, plus inpatient oral vancomycin or metronidazole treatment started at least 3 days after hospital admission. Individuals whose discharge records indicated age >18 years, and had available data on demographic and facility characteristics, use of medications, and specific procedure and diagnostic codes were included in the study. Multivariable generalized estimating equation models were used for analysis, with adjustments made for hospital and patient characteristics.

Of the facilities and individuals included, Hospital-onset C difficile showed an unadjusted rate of 7.3 per 10,000 patient-days (95% CI, 7.1-7.5), with total antibiotic use of 811 days of therapy/1000 patient-days (95% CI, 803-820). Variation in hospital-onset CDI rate correlated with bed size, the percentage of surgical discharges, rural or urban setting, teaching status, and census division. There was a 4.4% rise in hospital-onset CDI per 50 days of therapy/1000 patient-days rise in antibiotic usage.

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Hospital-onset CDI also increased by 2.1% with each 10 days of therapy/1000 patient-days rise in third-generation carbapenems or cephalosporins use, and 2.9% with each 10  days of therapy/1000 patient-days rise in fourth-generation carbapenems or cephalosporins use. Of 6 acute-care hospitals with at least a 30% drop in total use of antibiotics, there was a 33% (95% CI, 4%-53%) drop in hospital-onset CDI rates. Hospital-onset CDI also decreased by 8% if there was a ≥20% drop in fluoroquinolone use. There was a 13% decrease in hospital-onset CDI when there was a ≥20% drop in third- or fourth-generation cephalosporin use, though researchers did note that any decrease in third- or fourth-generation cephalosporin use corresponded with some decrease in CDI incidence.

Limitations to this study included the usage of administrative data, a lack of data on diagnostic practices and hospital infection control, and a lack of assessing for interactions between different antibiotic classes.

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The study researchers concluded that “facility-level antibiotic use in U.S. acute care hospitals is strongly associated with hospital-onset CDI rates. Furthermore, reductions in antibiotic use, either overall or focused reductions in use of fluoroquinolones and third- and fourth generation cephalosporins can reduce facility-level rates of [hospital-onset CDI].”


Kazakova SV, Baggs J, McDonald LC, et al. Association between antibiotic use and hospital-onset Clostridioides difficile infection in U.S. acute care hospitals, 2006-2012: an ecologic analysis [published online March 1, 2019]. Clin Infect Dis. doi: 10.1093/cid/ciz169