Antibiotic Stewardship Alone Not Sufficient for C Diff Infection Prevention, Study Finds

New research is shedding light on the need for C difficile infection (CDI) strategies beyond antibiotic stewardship, highlighting antibiotic exposure’s minimal impact on infection risk in asymptomatic carriers.1

The retrospective cohort study examined > 33,000 hospitalizations among 23,001 patients and found asymptomatic carriers had a greater hazard of CDI, with antibiotic exposure, particularly to amoxicillin and clavulanate and piperacillin and tazobactam, linked to increased infection risk. Of note, antibiotic exposure was not significantly associated with additional hazard among carriers, suggesting antibiotic stewardship may not effectively reduce CDI risk in this population.1

According to the US Centers for Disease Control and Prevention, Clostridioides difficile, a bacterium that causes diarrhea and colitis, is estimated to cause almost half a million infections in the US each year. Receipt of certain antimicrobials is associated with increased susceptibility to CDI.2

“Asymptomatic carriers of C difficile, ie, individuals with positive test results for the bacterium without exhibiting symptoms, present unique challenges in health care settings. These carriers not only act as potential reservoirs for transmission but also are at an elevated risk of progressing to clinical CDI,” Mayan Gilboa, MD, Infectious Control Unit, Sheba Medical Center in Israel, and colleagues wrote.1 “However, the specific interactions among antibiotic use, type, and duration of treatment in this high-risk group remain poorly understood.”

To evaluate the risk of CDI among asymptomatic carriers versus 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 which 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

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 (0.1%) 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 (hazard ratio [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 antibiotic exposure was not significantly associated with a further increase in CDI hazard (HR, 1.07; 95% CI, 0.73-1.58).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.html