3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (“statins”) reduce risk of atherosclerotic disease. However, statins need secondary bile acids, produced by the gut microbiota, for absorption. Our hypothesis was that a change in the gut microbiota induced by antibiotics might cause a decrease in statin absorption, and decreased statin effectiveness. Our objective was to study the association between antibiotic treatment and increased cholesterol level in statin users.

Case-crossover study, in which an individual serves as his own control, by comparing outcome risk among the same individual at different times, adjusting for time-dependent comorbidity index. The study is based on adherent statin users' cohort and two cohorts of patients not treated with statins, in Clalit Health Services. Exposure were antibiotic prescriptions dispensed in the 3 months prior to LDL-C measurements.

There were 25,496 statin users and 72,638 time-points. A significant association was found between LDL-C increase and exposure to macrolides and clindamycin, OR = 1.237 (1.138–1.345), p = 6.5*10−7, number needed to harm (NNH) = 19. There was no association between LDL-C increase and negative control objects such as anti-viral treatments; nor between LDL-C and exposure to antibiotics in non-statin users. As a secondary outcome, we have found an association between LDL-C increase and a following atherosclerotic ischemic event.

An increase in LDL-C in highly adherent statin users is associated with precedent macrolides or clindamycin treatment.