Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis.

BACKGROUND & AIMS: In the past decade, there has been a growing epidemic of Clostridium difficile infection (CDI). During this time, use of proton pump inhibitors (PPIs) has increased exponentially. We evaluated the association between PPI therapy and the risk of CDI by performing a meta-analysis. METHODS: We searched MEDLINE and 4 other databases for subject headings and text words related to CDI and PPI in articles published from 1990 to 2010. All observational studies that investigated the risk of CDI associated with PPI therapy and used CDI as an end point were considered eligible. Two investigators screened articles independently for inclusion criteria, data extraction, and quality assessment; disagreements were resolved based on consensus with a third investigator. Data were combined by means of a random-effects model and odds ratios were calculated. Subgroup and sensitivity analyses were performed based on study design and antibiotic use. RESULTS: Thirty studies (25 case-control and 5 cohort) reported in 29 articles met the inclusion criteria (n = 202,965). PPI therapy increased the risk for CDI (odds ratio, 2.15, 95% confidence interval, 1.81-2.55), but there was significant heterogeneity in results among studies (P < .00001). This association remained after subgroup and sensitivity analyses, although significant heterogeneity persisted among studies. CONCLUSIONS: PPI therapy is associated with a 2-fold increase in risk for CDI. Because of the observational nature of the analyzed studies, we were not able to study the causes of this association. Further studies are needed to determine the mechanisms by which PPI therapy might increase risk for CDI.

Diagnostic accuracy of real-time polymerase chain reaction in detection of Clostridium difficile in the stool samples of patients with suspected Clostridium difficile Infection: a meta-analysis.

BACKGROUND: Current detection methods for Clostridium difficile infection (CDI) can be time-consuming and have variable sensitivities. Real-time polymerase chain reaction (PCR) may allow earlier and more accurate diagnosis of CDI than other currently available diagnostic tests. A meta-analysis was performed to determine the diagnostic accuracy of real-time PCR. METHODS: We searched MEDLINE (Pubmed/Ovid) and 4 other online electronic databases (1995-2010) to identify diagnostic accuracy studies that compared PCR with cell culture cytotoxicity neutralization assay (CCCNA) or anaerobic toxigenic culture (TC) of C. difficile. Screening for inclusion, data extraction, and quality assessment were carried out independently by 2 investigators and disagreements resolved. Data were combined by means of a random-effects model, and summary receiver operating characteristic curves and diagnostic odds ratios were calculated. RESULTS: Nineteen studies (7392 samples) met our inclusion criteria. The overall mean sensitivity of PCR was 90% (95% confidence interval [CI]: 88%-91%), specificity 96% (CI: 96%-97%), positive likelihood ratio 26.89 (CI: 20.81-34.74), negative likelihood ratio 0.11 (CI: .08-.15), diagnostic odds ratio 278.23 (CI: 213.56-362.50), and area under the curve 0.98 (CI: .98-.99). Test accuracy depended on the prevalence of C. difficile but not on the reference test used. At C. difficile prevalence of <10%, 10%-20% and >20% the positive predictive value and the negative predictive value were 71%, 79%, 93% and 99%, 98% and 96%, respectively. CONCLUSIONS: Real-time PCR has a high sensitivity and specificity to confirm CDI. Overall diagnostic accuracy is variable and depends on CDI prevalence.