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Use of high-risk antibiotics in hospitals, such as cephalosporins, fluoroquinolones, carbapenems, and lincosamides, was linked with a greater risk of Clostridioides difficile in hospitals, researchers found.

After adjusting for confounders, for each 100-day increase in high-risk antibiotic use per 1,000 days present, risk of hospital-associated C. difficile infection rose 12% (RR 1.12, 95% CI 1.04-1.21), reported L. Clifford McDonald, MD, of the CDC, and colleagues, writing in , the journal of the Society for Healthcare Epidemiology of America.

"This highlights the importance of ongoing monitoring of antibiotic use in hospitals for patient safety as it relates to the effect of antibiotics on C. difficile infections," McDonald said in a statement.

The authors noted that antibiotic overuse is now being looked at as a major driver of C. difficile infections, especially prior research finding that around half of inpatients were prescribed an antibiotic and potentially 30% of those antibiotics were unnecessary, they said.

"In addition to the direct effects of antibiotics on [C. difficile infection] risk, antibiotics mediate carriage of C. difficile spores by asymptomatic carriers ... and are sources of transmission that may further increase the [C. difficile infection] burden in acute-care settings," the authors wrote.

Researchers examined data from 171 hospitals in 2016-2017 through the BD Institute Research Database. They defined 4 antibiotic classes as high risk based on prior research and guidelines that looked at specific antibiotics to treat C. difficile infection, they said: second-, third-, and fourth-generation cephalosporins, as well as fluoroquinolones, carbapenems, and lincosamides. The authors noted piperacillin/tazobactam was also evaluated, as some studies considered it "medium risk" for C. difficile infection.

Of the 171 study sites, the majority were non-teaching hospitals (61%), and about half were located in the southern U.S. Cephalosporins comprised about half of the most frequently used antibiotics, followed by fluoroquinolones (31.6%). There was a significant correlation between use of high-risk antibiotics and C. difficile infection, with higher correlation between the two observed in teaching versus non-teaching hospitals.

The authors found that the overall pooled hospital-associated C. difficile infection rate was 35 per 10,000 admissions, with a median of 33 per 10,000 across 171 hospitals. Not surprisingly, factors associated with higher rates of hospital-associated C. difficile infection included increased high-risk antibiotic use, larger proportions of patients older than age 65, longer average length of stay, and higher proton pump inhibitor use.

Limitations to the data include that the study is not representative of all U.S. hospitals and as an ecologic study, it does not depict causal relationships.

McDonald said in a statement that in the future, it will be important to look at the effect of antibiotic use on C. difficile infection and antibiotic resistance together versus separately.

"A facility can use the National Healthcare Safety Network Antibiotic Use and Resistance Module and interpret results using the standardized antibiotic administration ratio (SAAR) to have a better understanding of how antibiotics are being used and identify areas for improvement," he said.