(249) Decreased risk of clinical gallstone disease after antibiotics that kill or inhibit 7α-dehydroxylating-bacteria

Background: Clostridia species in the human gut can perform 7α-dehydroxylation, converting primary bile acids to secondary bile acids, which increase the risk of gallstones and possibly clinical gallstone disease (cGD). However, we lack population-level data on the impact of antibiotics that target 7α-dehydroxylating bacteria.

Objectives: To determine the risk of cGD after antibiotic exposure, hypothesizing that risk of cGD is decreased in people exposed to antibiotics that inhibit or kill 7α-dehydroxylating bacteria (e.g., amoxicillin).

Methods: We performed a retrospective, population-based cohort study with an active-comparator new-user design using US commercial MarketScan data (2015-19). The study population consisted of newly antibiotic-exposed adults aged ≥18 years receiving antibiotics in the outpatient setting. Patients with diagnosis of cGD up to 183 days prior to exposure or with a history of cholecystectomy were excluded. Based on their similar indications and contrasting impact on anti-7α-dehydroxylating bacteria, our primary comparisons were: 1) amoxicillin/clavulanate vs. trimethoprim/sulfamethoxazole, 2) amoxicillin vs. trimethoprim/sulfamethoxazole, and 3) amoxicillin vs. cephalosporins (1st to 5th generation). Our outcome of interest was diagnosis of cGD based on ICD-9-CM or ICD-10-CM codes. We calculated crude relative risks (RR, with 95% CIs) of cGD within 1 month after antibiotic exposure.

Results: The mean age of patients was 46.2 (+ 12.2) years, and 67% were female. Compared to comparator drugs, amoxicillin with or without clavulanate was associated with reduced risk of cGD: amoxicillin/clavulanate vs. trimethoprim/sulfamethoxazole (N=20,173), RR 0.74 (95% CI 0.69, 0.79); amoxicillin vs. trimethoprim/sulfamethoxazole (N=21,925), RR 0.59 (95% CI 0.55, 0.63); and amoxicillin vs. cephalosporins (N=25,747), RR 0.78 (95% CI 0.73, 0.83). This reduced risk was consistent across age and sex strata.

Conclusions: These findings provide novel insights into the relationship between the microbiome and cGD and support the hypothesis that anti-7α-dehydroxylating-bacteria antibiotics reduce the risk of cGD. If confirmed after completion of fully adjusted analyses, outcome validation, and replication in electronic health records data, they suggest that modification of the microbiome has promise as a preventive approach for reducing the risk of cGD, that should be evaluated further as means to avoid the need for gallbladder surgery.