Effect of Gastric Acid Suppression on Recurrence of Clostridium difficile-Associated Disease

Abstract

Purpose: Use of acid suppressants (proton pump inhibitors and H2 receptor antagonists) has been associated with increased incidence of Clostridium difficile-associated disease (CDAD). We hypothesized that gastric acid suppression may also be associated with increased recurrence of CDAD. The objective of the study was to evaluate the effect of acid suppression on the risk of recurrence in patients with CDAD. Methods: Study design: Retrospective observational study of patients admitted to a hospital with CDAD. Inclusion criteria: Age more than 18 years; CDAD diagnosed using either the ELISA-based toxin assay or pseudomembranes noted on endoscopy with histological confirmation or both. Two groups of patients were identified – cases and controls. Cases were patients on acid suppressants for any reason and controls were patients not taking any acid suppressant. CDAD was categorized as mild-moderate or severe based on the absence or presence of 2 or more of the following criteria: WBC >15,000, albumin <2 g/dL, ICU admission for CDAD, pseudomembranes noted on endoscopy and bowel wall thickening on CT scan. Exclusion criteria: Asymptomatic carriers, testing done on outpatient basis or at outlying hospitals, and incomplete medical records. Primary outcome: Recurrence rate (two or more episodes) of CDAD. Statistical analysis: Chi-square analysis. Results: A total of 558 were reviewed and 262 met study criteria. The mean age of the patient population was 68 years (SD + 16) with more females (153/262, 58.4%) than males (109/262, 41.6%). Most of the patients were Caucasians (249/262, 95%). Cases (199/262, 76%) and Controls (63/262, 24%) were matched based on the severity of illness. There was no difference in the recurrence rate of CDAD between mild-moderate cases (16/161, 10%) versus controls (7/55, 12.7%) (P= 0.61). Although the recurrence of CDAD in severe cases (12/38, 31.5%) was higher than those in the corresponding controls (1/8, 12.5%), this difference was not statistically significant (P= 0.4). However, using univariate analysis, age (67.2 + 15.7 with single infection and 73.8 + 16 with multiple recurrences) and severity were found to be independently associated with CDAD recurrence (P= 0.039 and 0.003, respectively). Conclusion: Acid suppressants did not seem to increase the risk of CDAD recurrence in our study. Age and severity of disease were found to be important risk factors for recurrence of CDAD. Larger prospective controlled trials should be undertaken to evaluate the risk of acid suppression on CDAD recurrence.