Antibiotics Increase Risk of C. Difficile Among Hospital Patients, Study Shows

It is well-established that antibiotics — especially the broad-spectrum ones — can increase the risk of Clostridioides difficile (C. difficile) by disrupting the gut microbiome, creating favorable conditions for the C. difficile bacteria to prosper. C. difficile is not a minor problem. It is a leading cause of infections acquired in healthcare settings. Infections cause diarrhea, which can be mild or severe, but serious cases can result in complications and even death. Care for patients with C. difficile stretches hospital resources and hits payers with additional bills for longer hospital stays and more intense services.

Although the broad outlines are understood, many of the details about which patients are vulnerable to C. difficile and which antibiotics are responsible remain unclear. A study conducted at the Sheba Medical Center, a tertiary medical center in Israel, shed new light on the subject. The findings, published in JAMA Open Network early last month, showed that being treated with antibiotics in the hospital was associated with a near doubling of the risk of C. difficile infection overall, but the risk was not uniform among the types of antibiotics. Exposure to piperacillin and tazobactam more than doubled the risk. There was also an association with exposure to amoxicillin and clavulanate. But lead author Mayan Gilboa, M.D., and her colleagues found no association between C. difficile and antibiotics that some previous research had shown increase the risk, including third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones and clindamycin. Gilboa and her colleagues said the difference may be explained by prescribing patterns, “antibiotic stewardship efforts” and limited exposure to those antibiotics.

Interestingly, though, their study did not find an association between C. difficile and exposure to antibiotic treatment among the 1,624 patients who screening tests showed were infected with C. difficile when they were first admitted to the hospital but were asymptomatic (patients were screened with rectal swabs that were tested for the presence of C. difficile with PCR tests). Other studies have shown otherwise. Gilboa and her coworkers said the discrepancy could be related to study design.

“In our study carriers were already at such an elevated baseline risk that changes in antibiotic exposure after hospitalization may have had a minimal influence on CDI [C. difficile infection],” they wrote in the discussion section of the paper. This explanation, they continued, fits with prior results showing that 40% of C. difficile “carriers” — people infected with the bacteria who are not experiencing symptoms — go on to develop symptomatic infections during hospitalization. Late-stage C. difficile carriage may be a predisease stage rather than “benign colonization,” Gilboa and her colleagues observed. Even though antibiotic exposure was a nonfactor for the carriers, they were far more likely to develop symptomatic C. difficile than the noncarriers in this study: 4.1% (67 of 1,624 carriers) developed C. difficile compared with just 0.1% (47 of 32,132) of the noncarriers.

Antibiotic stewardship

Results from this study showed that the risk of C. difficile infection increased each additional day of exposure to antibiotics. The researchers found that the risk stabilized and then increased after 14 days.

“Considering the growing literature supporting shorter antibiotic courses for various infections, along with the association between antibiotic use and CDI that appears more pronounced after day 14, duration of therapy should be a focus of antibiotic stewardship programs aimed at reducing CDI rates,” said Gilboa and her colleagues.