Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection.
BACKGROUND
The incidence and severity of Clostridium difficile infections are increasing. Acid-suppressive therapy has been suggested as a risk factor for C difficile, but this remains controversial.


METHODS
We conducted a pharmacoepidemiologic cohort study, performing a secondary analysis of data collected prospectively on 101 796 discharges from a tertiary care medical center during a 5-year period. The primary exposure of interest was acid suppression therapy, classified by the most intense acid suppression therapy received (no acid suppression, histamine(2)-receptor antagonist [H(2)RA] therapy, daily proton pump inhibitor [PPI], and PPI more frequently than daily).


RESULTS
As the level of acid suppression increased, the risk of nosocomial C difficile infection increased, from 0.3% (95% confidence interval [CI], 0.21%-0.31%) in patients not receiving acid suppressive therapy to 0.6% (95% CI, 0.49%-0.79%) in those receiving H(2)RA therapy, to 0.9% (95% CI, 0.80%-0.98%) in those receiving daily PPI treatment, and to 1.4% (1.15%-1.71%) in those receiving more frequent PPI therapy. After adjustment for comorbid conditions, age, antibiotics, and propensity score-based likelihood of receipt of acid-suppression therapy, the association persisted, increasing from an odds ratio of 1 (no acid suppression [reference]) to 1.53 (95% CI, 1.12-2.10) (H(2)RA), to 1.74 (95% CI, 1.39-2.18) (daily PPI), and to 2.36 (95% CI, 1.79-3.11) (more frequent PPI). Similar estimates were found with a matched cohort analysis and with nested case-control techniques.


CONCLUSIONS
Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection. This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection.
Howell
Michael D
MD
Silverman Institute for Healthcare Quality and Safety, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA. mhowell@bidmc.harvard.edu
Novack
Victor
V
Grgurich
Philip
P
Soulliard
Diane
D
Novack
Lena
L
Pencina
Michael
M
Talmor
Daniel
D
D000368:Aged; D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D001900:Boston / Q000453:epidemiology; D016022:Case-Control Studies; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000139:chemically induced* / Q000453:epidemiology; D003428:Cross Infection / Q000139:chemically induced* / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006635:Histamine H2 Antagonists / Q000009:adverse effects*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D016555:Matched-Pair Analysis; D015999:Multivariate Analysis; D057216:Propensity Score; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors