• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (39)  • Contact me when this article is cited  Related Content  • Related letter  • Related articles  • Similar articles in this journal  Topic Collections  • Bacterial Infections  • Infectious Diseases, Other  • Less Is More  • Comparative Effectiveness  • Drug Therapy  • Adverse Effects  • Drug Therapy, Other  • Gastroenterology  • Gastrointestinal Diseases  • Infectious Diseases  • Alert me on articles by topic  Social Bookmarking   What's this?

Michael D. Howell, MD, MPH; Victor Novack, MD, PhD; Philip Grgurich, PharmD; Diane Soulliard, PharmD; Lena Novack, PhD; Michael Pencina, PhD; Daniel Talmor, MD, MPH

Arch Intern Med. 2010;170(9):784-790.

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, histamine₂-receptor antagonist [H₂RA] 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 H₂RA 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) (H₂RA), 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.

Author Affiliations: Silverman Institute for Healthcare Quality and Safety (Dr Howell) and the Departments of Medicine (Dr Howell), Pharmacy (Dr Soulliard), and Anesthesia, Critical Care, and Pain Medicine (Dr Talmor), Beth Israel Deaconess Medical Center, Boston, Massachusetts; Departments of Medicine (Dr Howell) and Anesthesia, Critical Care, and Pain Medicine (Dr Talmor), Harvard Medical School, Boston; the Harvard Clinical Research Institute, Boston (Drs V. Novack, L. Novack, and Pencina); and the Department of Pharmacy, Froedtert Hospital, Milwaukee, Wisconsin (Dr Grgurich).

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

RELATED LETTER

Use of PPIs Are Not Associated With Mortality in Institutionalized Older People—Reply
J. Simon Bell, Timo E. Strandberg, and Kaisu H. Pitkälä
Arch Intern Med. 2011;171(9):866-867.
EXTRACT | FULL TEXT  

RELATED ARTICLES

Failing the Acid Test: Benefits of Proton Pump Inhibitors May Not Justify the Risks for Many Users
Mitchell H. Katz
Arch Intern Med. 2010;170(9):747-748.
EXTRACT | FULL TEXT  

Less Is More: How Less Health Care Can Result in Better Health
Deborah Grady and Rita F. Redberg
Arch Intern Med. 2010;170(9):749-750.
EXTRACT | FULL TEXT  

High-Dose vs Non–High-Dose Proton Pump Inhibitors After Endoscopic Treatment in Patients With Bleeding Peptic Ulcer: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Chih-Hung Wang, Matthew Huei-Ming Ma, Hao-Chang Chou, Zui-Shen Yen, Chih-Wei Yang, Cheng-Chung Fang, and Shyr-Chyr Chen
Arch Intern Med. 2010;170(9):751-758.
ABSTRACT | FULL TEXT  

Proton Pump Inhibitor Use, Hip Fracture, and Change in Bone Mineral Density in Postmenopausal Women: Results From the Women's Health Initiative
Shelly L. Gray, Andrea Z. LaCroix, Joseph Larson, John Robbins, Jane A. Cauley, JoAnn E. Manson, and Zhao Chen
Arch Intern Med. 2010;170(9):765-771.
ABSTRACT | FULL TEXT  

Proton Pump Inhibitors and Risk for Recurrent Clostridium difficile Infection
Amy Linsky, Kalpana Gupta, Elizabeth V. Lawler, Jennifer R. Fonda, and John A. Hermos
Arch Intern Med. 2010;170(9):772-778.
ABSTRACT | FULL TEXT  

Proton Pump Inhibitors for Prophylaxis of Nosocomial Upper Gastrointestinal Tract Bleeding: Effect of Standardized Guidelines on Prescribing Practice
Patrick S. Yachimski, Elizabeth A. Farrell, Daniel P. Hunt, and Andrea E. Reid
Arch Intern Med. 2010;170(9):779-783.
ABSTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Risk Factors Associated With Complications and Mortality in Patients With Clostridium difficile Infection
Morrison et al.
Clinical Infectious Diseases 2011;53:1173-1178.
ABSTRACT | FULL TEXT  

Clostridium difficile in the ICU: The Struggle Continues
Bobo et al.
Chest 2011;140:1643-1653.
ABSTRACT | FULL TEXT  

Safely Doing Less: A Missing Component of the Patient Safety Dialogue
Schroeder et al.
Pediatrics 2011;128:e1596-e1597.
FULL TEXT  

What you need to know when you prescribe a proton pump inhibitor
Norman and Hawkey
Frontline Gastro 2011;2:199-205.
ABSTRACT | FULL TEXT  

Elusive cause of hypomagnesaemia
Swaminathan and Wilson
BMJ 2011;343:d5087-d5087.
FULL TEXT  

Laboratory Testing for Clostridium difficile Infection: Light at the End of the Tunnel
Peterson et al.
Am J Clin Pathol 2011;136:372-380.
ABSTRACT | FULL TEXT  

The host immune response to Clostridium difficile
Kelly and Kyne
J Med Microbiol 2011;60:1070-1079.
ABSTRACT | FULL TEXT  

Severe occult upper gastrointestinal haemorrhage--a case report
Agha and Agha
QJM 2011;0:hcr085v1-hcr085.
FULL TEXT  

Acid-Suppressive Medication Use and the Risk for Nosocomial Gastrointestinal Tract Bleeding
Herzig et al.
Arch Intern Med 2011;171:991-997.
ABSTRACT | FULL TEXT  

Opportunities to Decrease Inappropriate Uses of Proton Pump Inhibitors: Comment on "Proton Pump Inhibitor Use and the Antifracture Efficacy of Alendronate"
Katz
Arch Intern Med 2011;171:1004-1005.
FULL TEXT  

Use of PPIs Are Not Associated With Mortality in Institutionalized Older People--Reply
Bell et al.
Arch Intern Med 2011;171:866-867.
FULL TEXT  

Pharmacology Review: Pharmacotherapy for Gastroesophageal Reflux Disease
Hibbs
Neoreviews 2011;12:e159-e166.
ABSTRACT | FULL TEXT  

Reducing NSAID-induced gastrointestinal complications
DTB 2011;49:18-21.
ABSTRACT | FULL TEXT  

Proton pump inhibitor side effects and drug interactions: Much ado about nothing?
MADANICK
Cleveland Clinic Journal of Medicine 2011;78:39-49.
ABSTRACT | FULL TEXT  

Proton-Pump Inhibitor Dosing and Negative Consequences
JWatch General 2010;2010:2-2.
FULL TEXT  

Failing the Acid Test: Benefits of Proton Pump Inhibitors May Not Justify the Risks for Many Users
Katz
Arch Intern Med 2010;170:747-748.
FULL TEXT  

Less Is More: How Less Health Care Can Result in Better Health
Grady and Redberg
Arch Intern Med 2010;170:749-750.
FULL TEXT