Combined use of antibiotics and PPIs tied to increased risk of Clostridioides difficile infection

The use of PPIs and antibiotics each has been independently associated with an increased CDI risk in several studies, few studies have examined the potential effects on CDI risk, when used in combination. Considering this, Nele Brusselaers, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden, and colleagues aimed to assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence.

For this purpose, they conducted a population-based study comprising 43 152 patients with CDI diagnosis in Sweden (2006–2019), and 355 172 matched population controls without CDI. The impact of PPIs and antibiotics on CDI risk and recurrence was explored for recent (0–30 days) and preceding (31–180 days) use before their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) after adjustment for comorbidities, demographics, and other drugs.

The study led to the following findings:

• Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51] on CDI risk was stronger than the individual effects [ORAB = 15.37; ORPPI = 2.65]. Results were less pronounced for exposure during the preceding months.
• Dose–response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32; ORPPI = 1.65 per prescription increase].
• Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30] and preceding [ORAB = 1.23; ORPPI = 1.12] use also affected the risk of recurrence yet without significant interaction between both.
• Recent macrolides/lincosamides/streptogramins; other antibacterials, including nitroimidazole derivates; non-penicillin beta-lactams and quinolones showed the strongest association with CDI risk and recurrence, specifically for recent use.
• PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes.

"Our findings stress the need to reconsider the risk-benefit of both PPIs and antibiotics, which are both still over-prescribed," the researchers wrote. In addition, they also stressed the importance of investigating the impact of these dispensed prescriptions on the odds of a recurrent episode, since antibiotics are also used for CDI treatment and the long-term safety and efficacy of the treatment.

"Exposure to systemic antibiotics and PPI use were associated with CDI risk and recurrence, particularly when combined," they concluded.

Reference:

Moreels, N., Boven, A., Gressani, O., Andersson, F. L., Vlieghe, E., Callens, S., Engstrand, L., Simin, J., & Brusselaers, N. The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence. Journal of Antimicrobial Chemotherapy. https://doi.org/10.1093/jac/dkae012