Probiotic Use Ineffective for Primary Prevention of Clostridioides difficile Infection in Select Hospitalized Patients

Clostridioides difficile bacteria
Illustration of the bacteria Clostridioides difficile. These rod shaped bacteria have flagella, which are used for motility. Clostridioides difficile (formerly known as Clostridium difficile) are anaerobic bacteria prevalent in soil. In humans, the bacteria can become established in the colon and disrupt the normal gut microbiota, particularly in people taking antibiotics. Toxins released by Clostridioides difficile can produce diarrhoea and inflammation.
A team of investigators evaluated outcomes following probiotic use for primary prevention of Clostridioides difficile infection in hospitalized patients.

The use of a 3-strain Lactobacillus probiotic preparation for primary prevention of Clostridioides difficile infection (CDI) was not found to be beneficial in patients aged 51 years and older receiving antibiotics in a setting with relatively low baseline CDI rates, according to findings of a multicenter, quasiexperimental before-and-after study published in the journal of Clinical Infectious Diseases.

The investigators created an electronic medical record best practice alert that prompted prescribers to order probiotic capsules, containing 100 billion colony forming units of probiotic, for eligible patients. Eligible patients included those at increased risk for CDI due to age older than 50 years, those for whom systemic antibiotic treatment was initiated with an anticipated need of more than 48 hours, and those able to take medications by mouth. To ensure patient safety, the alert was suppressed for patients at high risk for invasive Lactobacillus infection. Hospital guidelines directed that the probiotic capsules be initiated within 12 hours of the initial antibiotic dose and continued daily during and 5 days after discontinuation of antibiotic therapy.

The 13-month baseline period was from April 1, 2018, to April 30, 2019, and the 13-month intervention period was from June 1, 2019, to June 30, 2020. Standard infection ratios (SIR) for CDI were compared preintervention and postintervention overall and for each participating hospital as reported to the Centers for Disease Control and Prevention National Healthcare Safety Network.

The CDI SIR decreased at all hospitals from preintervention to postintervention. However, the study authors found “when evaluating quarterly CDI incidence per 10,000 patient-days, combined for all hospitals, there was a pre-intervention decrease in CDI with a significant immediate level decrease, but followed by a gradual increase in CDI incidence post-implementation.”

There were 17,536 patients in the preintervention group and 15,023 patients in the postintervention group; 0.75% pre-intervention patients had CDI compared with 1.02% postintervention patients (P =.01). Statistical analysis showed the odds of CDI to be 1.4-fold greater in the postintervention group compared with the preintervention group (95% CI, 1.13-1.84; P =.003). The unadjusted relative risk for CDI in patients who received probiotics compared with those who did not was 1.48 (95% CI, 1.01-2.16; P =.043).

Limitations of this study include changes in the C difficile testing strategy during the study period that may have omitted potentially qualified patients, as well as an inability to evaluate adherence to probiotic use in discharged patients.

“In this study of systematic computerized clinical decision support-facilitated probiotic use for the primary prevention of CDI, probiotics were not found to be protective. In fact, incidence of CDI was higher in the post-intervention group compared to pre-intervention, and in a propensity-matched analysis, although not statistically significant, CDI risk was greater among patients who received probiotics versus patients who did not,” the study authors concluded.


Heil EL, Harris AD, Brown CH, et al. A multi-center evaluation of probiotic use for the primary prevention of Clostridioides difficile infection. Clin Infect Dis. Published online May 11, 2021. doi:10.1093/cid/ciab417