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Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis.
Am J Gastroenterol 2012; 107(7):1011-9AJ

Abstract

OBJECTIVES

Several studies have raised concern regarding the possible association between proton-pump inhibitors (PPIs) and Clostridium difficile infection (CDI). We aimed to perform a systematic review of incident and recurrent CDI in PPI users, and to evaluate the relative impact of concurrent antibiotic use, or switching acid suppression to histamine-2-receptor antagonists (H2RAs).

METHODS

We searched MEDLINE and EMBASE from inception to December 2011 for controlled observational studies that reported on the risk of CDI with and without PPI use. We performed random effects meta-analysis and assessed statistical heterogeneity using the I(2) statistic.

RESULTS

We included 42 observational studies (30 case-control, 12 cohort) totalling 313,000 participants overall. Pooled analysis of 39 studies showed a statistically significant association between PPI use and risk of developing CDI, odds ratio (OR) 1.74 (95% confidence interval (CI) 1.47-2.85, P<0.001, I(2)=85%) compared with non-users. A pooled analysis of three studies showed a significant associated risk of recurrent CDI associated with PPIs, OR 2.51 (95% CI 1.16-5.44, P=0.005, I(2)=78%). Subgroup analysis failed to fully clarify the source of the substantial statistical heterogeneity. Adjusted indirect comparison demonstrated that use of H2RAs as an alternative carried a lower-risk OR 0.71 (95% CI 0.53-0.97) compared with PPIs. Conversely, concomitant use of PPI and antibiotics conferred a greater-risk OR 1.96 (95% CI 1.03-3.70) above that of PPIs alone. For PPI and antibiotics, the Rothman's synergy index was 1.36 and attributable proportion of risk from interaction 0.19, indicating an increased risk from interaction beyond the effects of each drug alone.

CONCLUSIONS

Despite the substantial statistical and clinical heterogeneity, our findings indicate a probable association between PPI use and incident and recurrent CDI. This risk is further increased by concomitant use of antibiotics and PPI, whereas H2RAs may be less harmful.

Authors+Show Affiliations

Norwich Medical School, University of East Anglia, Norwich, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

22525304

Citation

Kwok, Chun Shing, et al. "Risk of Clostridium Difficile Infection With Acid Suppressing Drugs and Antibiotics: Meta-analysis." The American Journal of Gastroenterology, vol. 107, no. 7, 2012, pp. 1011-9.
Kwok CS, Arthur AK, Anibueze CI, et al. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107(7):1011-9.
Kwok, C. S., Arthur, A. K., Anibueze, C. I., Singh, S., Cavallazzi, R., & Loke, Y. K. (2012). Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. The American Journal of Gastroenterology, 107(7), pp. 1011-9. doi:10.1038/ajg.2012.108.
Kwok CS, et al. Risk of Clostridium Difficile Infection With Acid Suppressing Drugs and Antibiotics: Meta-analysis. Am J Gastroenterol. 2012;107(7):1011-9. PubMed PMID: 22525304.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. AU - Kwok,Chun Shing, AU - Arthur,Aaron Kobina, AU - Anibueze,Chukwudubem Ifeanyichukwu, AU - Singh,Sonal, AU - Cavallazzi,Rodrigo, AU - Loke,Yoon Kong, Y1 - 2012/04/24/ PY - 2012/4/25/entrez PY - 2012/4/25/pubmed PY - 2012/10/25/medline SP - 1011 EP - 9 JF - The American journal of gastroenterology JO - Am. J. Gastroenterol. VL - 107 IS - 7 N2 - OBJECTIVES: Several studies have raised concern regarding the possible association between proton-pump inhibitors (PPIs) and Clostridium difficile infection (CDI). We aimed to perform a systematic review of incident and recurrent CDI in PPI users, and to evaluate the relative impact of concurrent antibiotic use, or switching acid suppression to histamine-2-receptor antagonists (H2RAs). METHODS: We searched MEDLINE and EMBASE from inception to December 2011 for controlled observational studies that reported on the risk of CDI with and without PPI use. We performed random effects meta-analysis and assessed statistical heterogeneity using the I(2) statistic. RESULTS: We included 42 observational studies (30 case-control, 12 cohort) totalling 313,000 participants overall. Pooled analysis of 39 studies showed a statistically significant association between PPI use and risk of developing CDI, odds ratio (OR) 1.74 (95% confidence interval (CI) 1.47-2.85, P<0.001, I(2)=85%) compared with non-users. A pooled analysis of three studies showed a significant associated risk of recurrent CDI associated with PPIs, OR 2.51 (95% CI 1.16-5.44, P=0.005, I(2)=78%). Subgroup analysis failed to fully clarify the source of the substantial statistical heterogeneity. Adjusted indirect comparison demonstrated that use of H2RAs as an alternative carried a lower-risk OR 0.71 (95% CI 0.53-0.97) compared with PPIs. Conversely, concomitant use of PPI and antibiotics conferred a greater-risk OR 1.96 (95% CI 1.03-3.70) above that of PPIs alone. For PPI and antibiotics, the Rothman's synergy index was 1.36 and attributable proportion of risk from interaction 0.19, indicating an increased risk from interaction beyond the effects of each drug alone. CONCLUSIONS: Despite the substantial statistical and clinical heterogeneity, our findings indicate a probable association between PPI use and incident and recurrent CDI. This risk is further increased by concomitant use of antibiotics and PPI, whereas H2RAs may be less harmful. SN - 1572-0241 UR - https://www.unboundmedicine.com/medline/citation/22525304/Risk_of_Clostridium_difficile_infection_with_acid_suppressing_drugs_and_antibiotics:_meta_analysis_ L2 - http://Insights.ovid.com/pubmed?pmid=22525304 DB - PRIME DP - Unbound Medicine ER -