Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis.
OBJECTIVE
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.
Department of Neurological Surgery, Neurological Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. deshpaa@ccf.org
Abhishek
A
Deshpande
Chaitanya
C
Pant
Vinay
V
Pasupuleti
David D K
DD
Rolston
Anil
A
Jain
Narayan
N
Deshpande
Priyaleela
P
Thota
Thomas J
TJ
Sferra
Adrian V
AV
Hernandez
D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000453:epidemiology* / Q000382:microbiology*; D006801:Humans; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D018570:Risk Assessment
D054328:Proton Pump Inhibitors