Comparison of Different Antibiotics and the Risk for Community-Associated Clostridioides difficile Infection: A Case-Control Study

Abstract

Background: Antibiotics are the greatest risk factor for Clostridioides difficile infection (CDI). Risk for CDI varies across antibiotic types and classes. Optimal prescribing and stewardship recommendations require comparisons of risk across antibiotics. However, many prior studies rely on aggregated antibiotic categories or are underpowered to detect significant differences across antibiotic types. Using a large database of real-world data, we evaluate community-associated CDI risk across individual antibiotic types.

Methods: We conducted a matched case-control study using a large database of insurance claims capturing longitudinal health care encounters and medications. Case patients with community-associated CDI were matched to 5 control patients by age, sex, and enrollment period. Antibiotics prescribed within 30 days before the CDI diagnosis along with other risk factors, including comorbidities, health care exposures, and gastric acid suppression were considered. Conditional logistic regression and a Bayesian analysis were used to compare risk across individual antibiotics. A sensitivity analysis of antibiotic exposure windows between 30 and 180 days was conducted.

Results: We identified 159 404 cases and 797 020 controls. Antibiotics with the greatest risk for CDI included clindamycin and later-generation cephalosporins, and those with the lowest risk included minocycline and doxycycline. We were able to differentiate and order individual antibiotics in terms of their relative level of associated risk for CDI. Risk estimates varied considerably with different exposure windows considered.

Conclusions: We found wide variation in CDI risk within and between classes of antibiotics. These findings ordering the level of associated risk across antibiotics can help inform tradeoffs in antibiotic prescribing decisions and stewardship efforts.

Keywords: CDI; Clostridioides difficile infection; antibiotics; case–control study; outpatient; risk factors; stewardship.

Graphical Abstract

Figure 1.

Visual comparison of effect estimates across antibiotic types, grouped by antibiotic class. Point estimates are depicted by the circle and 95% credible intervals by the line segments. Exact values can be found in Table 2.

Figure 2.

Posterior probabilities of the pairwise comparisons of odds ratios across antibiotic types. The values represent the posterior probability that the odds ratio of the antibiotic in the row is less than the odds ratio of the antibiotic in the column. For example, the posterior probability that the odds ratio for cefixime is less than that of cefdinir is roughly 29.0%, while the posterior probability that the odds ratio for cefdinir is less than that of cefixime is roughly 71.0%. Results are ordered by effect size based on the 30-day exposure window. Only exact probability values between 5% and 95% are reported; Supplementary Figure 1 provides complete values for all cells <5% and >95%.

Figure 3.

Results of sensitivity analysis for effect estimates across antibiotic types using different exposure windows to capture prior antibiotic exposure. Exact values are reported in Supplementary Table 3. Results are ordered by effect size based on the 30-day exposure window. In general, effect estimates move toward the null value of 1 as the exposure window increases.