Do Statins Protect against Clostridum difficile Associated Diarrhea?

Abstract

Purpose: Statins are one of the most commonly prescribed classes of drugs in the United States. Clostridium difficile -associated diarrhea (CDAD) is the most common cause of nosocomial diarrhea in the United States with increasing incidence and mortality rates. In this study, we aim to determine if there is a clinically significant association between community or health care acquired CDAD and statin use. Methods: A retrospective case-control study was conducted in an urban teaching hospital to determine the association between CDAD and statin use. Over a 2-year period, all patients with CDAD (n=188) were included as cases and further categorized into community-acquired (CA) CDAD (n=23) and healthcare acquired (HA) CDAD (n=165). Age and sex-matched controls were randomly selected in a 2:1 ratio. In the subgroup analysis, the ratio of controls to CA-CDAD and HA-CDAD cases were 10:1 and 2:1, respectively. The use of statins prior to admission as well as during hospitalization was compared between cases and controls and odds ratios (OR) were calculated. The calculated odds ratios (OR) were adjusted for multiple possible confounding variables, including chronic kidney disease (CKD), exposure to proton pump inhibitors (PPI), Histamine-2 antagonists (H2A) and antibiotics, using multiple logistic regression analysis. Results: For all cases, OR suggested that statins are associated with a protective effect against CDAD [OR, unadjusted: 0.62 (0.43 - 0.90), p=0.013]. After adjustment for confounding variables, the OR was sensitive to non-fluoroquinolone antibiotics but to none of the other covariates. For HA-CDAD, the unadjusted OR was 0.55 [(0.36 to 0.86); p=0.009], and was also only sensitive to non-fluoroquinolone antibiotics. For CA-CDAD, no significant associations were observed. Conclusion: Statins may protect against the known risk factors for CDAD like CKD, PPI and H2A, as observed in one prior study. Antibiotics, especially non-fluoroquinolones, seem to mitigate the protective effect of statins. Whether these antibiotics interact with the metabolism of statins remains to be determined. Furthermore, statin use does not seem to have any significant relation with CA-CDAD. Further studies are needed to investigate this association.