To evaluate the risk of CDI among asymptomatic carriers vs noncarriers of C difficile and whether it is associated with antibiotic exposure, investigators conducted a retrospective cohort study between June 2017 and June 2023, assessing hospitalizations from Sheba Medical Center in Ramat Gan, Israel, a center that routinely screens for C difficile in high-risk patients admitted to internal medicine.1
Eligible patients were adults who were hospitalized in internal medicine wards and deemed high risk for C difficile carriage due to reasons like hospitalization within the past 6 months or transfer from another hospital or a long-term-care facility.1
All patients were followed up from 2 days after hospitalization until death, discharge, day 21 of the hospitalization, admission to the ICU, or CDI, whichever was earliest. The primary outcome was the development of CDI, as confirmed by laboratory testing for C difficile. Antibiotic exposure was assessed as a time-varying variable.1
What You Need To Know
Asymptomatic C difficile carriers have a higher risk of developing CDI, despite antibiotic exposure not significantly increasing this risk among carriers.
Antibiotic exposure, particularly to amoxicillin, clavulanate, piperacillin, and tazobactam, is linked to increased CDI risk in the general cohort.
The study highlights the need for strategies beyond antibiotic stewardship to address the high baseline CDI risk in asymptomatic carriers.
In total, the study included 33,756 hospitalizations among 23,001 patients, the majority of whom were male (52.8%) with a median age of 78 (interquartile range [IQR], 68-87) years. A total of 1624 (4.8%) admissions had a positive screening result for C difficile and were defined by investigators as carriers.1
Overall, 67 of 1624 (4.1%) carriers and 47 of 32,132 (.1%) noncarriers with negative screening results developed CDI.1
Among carriers, 251 CDI tests were sent (15.5%) compared with 2067 tests among noncarriers (6.4%). Despite more frequent testing in carriers, investigators noted the positivity rate was markedly higher at 26.7% (67 of 251) in carriers vs 2.3% (46 of 2067) in noncarriers.1
Among the entire cohort, exposure to any antibiotic was associated with an increased risk of CDI (HR, 1.98; 95% CI, 1.24-3.16), with each additional day of exposure to antibiotics having an HR of 1.08 (95% CI, 1.03-1.13). Exposure to piperacillin and tazobactam was associated with increased risk (HR, 2.18; 95% CI, 1.41-3.36), with each additional day having an HR of 1.13 (95% CI, 1.07-1.20).1
Further analysis revealed a positive C difficile screening result at admission was associated with a high risk of infection (HR, 27.5; 95% CI, 18.7-40.3). Among asymptomatic carriers, investigators pointed out that antibiotic exposure was not significantly associated with a further increase in CDI hazard (HR, 1.07; 95% CI, .73-1.58).1
“While antibiotic stewardship is crucial for reducing CDI in general, additional approaches are needed for carriers to mitigate their substantially high baseline risk,” investigators concluded.1 “Further research should explore modifiable factors beyond antibiotic use to improve outcomes in patients with CDI and to reduce the overall burden of CDI in health care settings.”
References
1. Gilboa M, Regev-Yochay G, Meltzer E, et al. Antibiotic use and the risk of hospital-onset Clostridioides difficile infection. JAMA Netw Open. 2025;8(8):e2525252. doi:10.1001/jamanetworkopen.2025.25252
2. US Centers for Disease Control and Prevention. About C. diff. December 18, 2024. Accessed August 11, 2025. https://www.cdc.gov/c-diff/about/index.ht