Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease.
BACKGROUND
Recent reports suggest an increasing occurrence and severity of Clostridium difficile-associated disease. We assessed whether the use of gastric acid-suppressive agents is associated with an increased risk in the community.


OBJECTIVE
To determine whether the use of gastric acid-suppressive agents increases the risk of C difficile-associated disease in a community population.


METHODS
We conducted 2 population-based case-control studies using the United Kingdom General Practice Research Database (GPRD). In the first study, we identified all 1672 cases of C difficile recorded between 1994 and 2004 among all patients registered for at least 2 years in each practice. Each case was matched to 10 controls on calendar time and the general practice. In the second study, a subset of these cases defined as community-acquired, that is, not hospitalized in the prior year, were matched on practice and age with controls also not hospitalized in the prior year.


METHODS
The incidence of C difficile and risk associated with gastric acid-suppressive agent use.


RESULTS
The incidence of C difficile in patients diagnosed by their general practitioners in the General Practice Research Database increased from less than 1 case per 100,000 in 1994 to 22 per 100,000 in 2004. The adjusted rate ratio of C difficile-associated disease with current use of proton pump inhibitors was 2.9 (95% confidence interval [CI], 2.4-3.4) and with H2-receptor antagonists the rate ratio was 2.0 (95% CI, 1.6-2.7). An elevated rate was also found with the use of nonsteroidal anti-inflammatory drugs (rate ratio, 1.3; 95% CI, 1.2-1.5).


CONCLUSIONS
The use of acid-suppressive therapy, particularly proton pump inhibitors, is associated with an increased risk of community-acquired C difficile. The unexpected increase in risk with nonsteroidal anti-inflammatory drug use should be investigated further.
Dial
Sandra
S
Division of Critical Care and Respiratory and Clinical Research, Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec. sandra.dial@mcgill.ca
Delaney
J A C
JA
Barkun
Alan N
AN
Suissa
Samy
S
D000368:Aged; D000863:Antacids / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000453:epidemiology* / Q000209:etiology; D017714:Community-Acquired Infections / Q000453:epidemiology*; D015897:Comorbidity; D003967:Diarrhea / Q000382:microbiology; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology; D005260:Female; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology
D000863:Antacids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors