Shedding Light on the C. difficile Landscape: Changing patterns of CDI ribotypes and the association between antibiotic use and hospital-onset CDI

Reviewed by: James “Brad” Cutrell, MD, UT Southwestern Medical Center; S. Schaeffer Spires, MD, Duke University School of Medicine

Two recent epidemiologic studies “shed” important light on the changing epidemiology of Clostridioides difficile infections and its relationship to antibiotic use. First, Herbert and colleagues studied stool samples from 5 major acute hospitals and primary care centers in West London, from August 2011 through June 2013.  This was a part of a larger study to routinely ribotype all C. difficile isolates and evaluate the impact of various prevention strategies.  This current study linked ribotype results with clinical, demographic and laboratory data to determine if any adverse outcomes were associated with particular ribotypes.  The primary outcome was 30-day all-cause mortality with secondary outcomes of length of stay and “biomarkers” such as CRP, albumin, leukocyte count, and serum creatinine.  Out of 758 PCR toxin B positive patients, the most common ribotypes were RT002 and RT015 (combined for 22.5%), while the oft-cited RT027 was isolated only in 0.7% patients.  C. difficile infections caused by RT220 demonstrated a reduced 30-day survival, with an all-cause mortality at 30 days of 41.2% (7 of 17 patients) for RT220 compared with 21.9% for RT002/RT015 (and 17% for all other ribotypes). RT220 was associated with higher median CRP (P=0.008) and a trend towards lower albumin. There was no difference in creatinine levels and leukocyte counts.  This study highlights the changing proportion of isolates RT027 in England, and it may be the first study reporting the increased 30-day mortality and acute phase response associated with RT220.

Second, Kazakova and colleagues at the Centers for Disease Control and Prevention analyzed the association of antibiotic use and hospital-onset C. difficile infections (HO-CDI) in 549 acute care hospitals reporting their data into the Truven Health MarketScan Hospital Drug Database from 2006 to 2012. HO-CDI was defined by discharge ICD-9 codes and treatment with metronidazole or oral vancomycin > 3 days after admission. Over the study period, unadjusted annual HO-CDI rates and total antibiotic use (AU) were 7.3 per 10,000 patient-days (PD) and 811 days of therapy (DOT) per 1000 PD, respectively. For every increase in AU by 50 DOT/1000 PD, HO-CDI rates increased by 4.4%. Smaller increases (10 DOT/1000 PD) in prescribing of high-risk antibiotic classes such as third- and fourth generation cephalosporins or carbapenems led to increases in HO-CDI rates by 2.1% and 2.9%, respectively. In monthly time-series analysis over the study, most hospitals’ AU remained flat or slightly increased over time; however, the minority of hospitals (n=6) that achieved > 30% reductions in total AU demonstrated a 33% reduction in HO-CDI rates. Limitations of the study include its reliance on administrative coding for CDI diagnoses and lack of information about hospital changes in CDI diagnostic testing or infection control/antibiotic stewardship practices over the study.

These two studies provide infection control practitioners and antibiotic stewards a helpful window on the changing epidemiology of CDI infections, potential new associations of ribotype 220 with worse clinical outcomes, and an estimate of the impact of total and high-risk antibiotic use reductions on HO-CDI rates.  


  1. Herbert R, Hatcher J, Jauneikaite E, et al. Two-year analysis of Clostridium difficile ribotypes associated with increased severity. J Hosp Infect. 2019;103(4):388-394. 
  2. Kazakova S, Baggs J, McDonald LC, et al. Association between antibiotic use and hospital-onset Clostridioides difficile infection in US acute care hospitals, 2006-2012: An ecologic analysis. Clin Infect Dis. 2020; 70(1):11-8.
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