Woelfel, Joseph A.

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University of the PacificScholarly CommonsSchool of Pharmacy and Health Sciences FacultyArticlesThomas J. Long School of Pharmacy and HealthSciences12-1-2004Community-acquired pneumonia risk with acid-suppressive drugsJoseph A. WoelfelUniversity of the Pacific, jwoelfel@pacific.eduFollow this and additional works at: https://scholarlycommons.pacific.edu/phs-facarticlesPart of the Pharmacy and Pharmaceutical Sciences CommonsThis Article is brought to you for free and open access by the Thomas J. Long School of Pharmacy and Health Sciences at Scholarly Commons. It hasbeen accepted for inclusion in School of Pharmacy and Health Sciences Faculty Articles by an authorized administrator of Scholarly Commons. Formore information, please contact mgibney@pacific.edu.Recommended CitationWoelfel, J. A. (2004). Community-acquired pneumonia risk with acid-suppressive drugs. Pharmacist’s Letter & Prescriber’s Letter,20(12), 1–3.https://scholarlycommons.pacific.edu/phs-facarticles/74 More. . . Copyright © 2004 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone:  209-472-2240 ~ Fax:  209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com  ®  ®  Detail-Document #201207 −This Detail-Document accompanies the related article published in− PHARMACIST’S LETTER / PRESCRIBER’S LETTER December 2004 ~ Volume 20 ~ Number 201207   Community-Acquired Pneumonia Risk with Acid-Suppressive Drugs Lead author: Joseph A. Woelfel, Ph.D., FASCP, R.Ph., Assistant Editor  Background Acid suppressive drugs, one of the most frequently prescribed drug classes, continue to grow in sales.1  Yet their use is not without risk.2 The normal pH of the stomach is a host defense and barrier to ingested pathogens.3  Bacterial overgrowth and colonization with upper gastrointestinal tract bacteria have been identified in studies with acid-inhibitory therapy.3,4  Acid-suppressing drugs are associated with bacterial overgrowth in the stomach and influenza viruses in the gastric mucosa.3,5  Studies have also shown that bacterial overgrowth depends on the intensity of inhibition of gastric acid secretion and corresponding increase in pH.  Both H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) effectively raise gastric pH.  Proton pump inhibitors have greater inhibition of gastric acid secretion compared with H2 receptor antagonists.4,6 Colonized oral secretions can be aspirated into the lungs and establish pneumonia.7    Citation Laheij RJ, Sturkenboom MC, Hassing R, et al.  Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs.  JAMA 2004;292:1955-60.  Methods Complete medical records for approximately half a million patients were accessed from the Integrated Primary Care Information project, a Dutch general practice research database.  The seven-year study included all patients with at least a one-year recorded history.  All participants were followed once they had a one-year history until the study ended, or until they had pneumonia, died, or moved out of the practice area.  All those with a pre-study pneumonia diagnosis were excluded.  All patients exposed to acid-suppressive therapy were compared to those who did not receive this therapy in the study period relative to their incidence of community-acquired pneumonia.  Incidence rates were calculated for exposed and unexposed participants.  To prevent confounding by antagonist indication, a nested case-control analysis of patients with pneumonia and using acid-suppressive drugs prior to or at the time of contracting pneumonia was conducted.    Results A total of 364,683 suppressive therapy exposed and unexposed patients were identified.  Person-time of exposure was calculated on the basis of person-years.  Overall, 5.3% of these individuals were exposed to suppressive drugs.  This represented 7562 person-years.  During the study period, 185 cases of radiographic or sputum culture confirmed-pneumonia occurred.  The incidence rate of pneumonia in acid-suppressive users was 2.45 and for non-suppressive participants the rate was 0.6 per 100 person-years. The adjusted relative risk for pneumonia for those currently using PPIs compared with those who stopped using PPIs was 1.89 (95% confidence interval, 1.36 to 2.62).  H2RA current users had a 1.63 adjusted relative risk for pneumonia (95% confidence interval, 1.07 to 2.48) compared with those who stopped their use.   A significant dose response was observed in PPI users taking more than one dose per day.  They had a 2.3-fold increased risk of pneumonia compared with past acid-suppressive drug users.  This dose response was not observed with H2RAs.    Author Conclusions Both H2RA and PPI acid-suppressive drugs are associated with an increase in community-acquired pneumonia risk.  This association probably results from their effective suppression of gastric pH which facilitates opportunistic infection by intestinal bacterial and viral organisms.   (Detail-Document #201207:  Page 2 of 3) More. . . Copyright © 2004 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone:  209-472-2240 ~ Fax:  209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com  Commentary The availability of acid-suppressive therapy is a major factor in the effective treatment of gastrointestinal ulcerative disease.  The rational use of these agents is associated with both efficacy and safety.  They represent a major milestone for improvement of the quality of life in patients suffering from these common disorders. As demonstrated in this study, despite their safety and efficacy, acid-suppressive agents can present risk for certain patients.   In another study of 700 patients by Laheij RJ, et al, those using acid-suppressive drugs were 2.34 times more likely (95% confidence interval, 1.4 to 4.1) than non-suppressive users to have clinical signs of infection.  They also visited a physician 3.72 times more often (95% confidence interval, 2.1 to 6.8) for an infection and received an antibiotic 4.19 times more often (95% confidence interval, 2.2 to 8.1) compared with non-suppressive users.8 In a recent investigation, both cohort and case-controlled studies were undertaken to assess acid-suppressive therapy as a risk factor for C. difficile infection.  C. difficile diarrhea developed in 6.8% of the 1,187 cohort patients.  Of the patients who received antibiotics and a PPI, 9.3% developed C. difficile diarrhea, whereas those who received antibiotics but no PPI experienced a 4.4% incidence (RR 2.1, 95% CI 1.4 to 3.4).  The relative risk of C. difficile was higher in patients receiving PPIs compared with H2RA recipients (OR 2.1, 95% CI 1.2 to 3.5 vs. OR 1.1, 95% CI 0.4 to 3.4).9   In the case-control study, 94 patients developed C. difficile diarrhea.  The case and control subjects were similar in age, number and type of antibiotic, and comorbidity factors.  Of the cases, 64% were receiving PPIs as compared with 36% of the controls (unadjusted OR 3.1, 95% CI 1.7 to 5.6).9  These authors concluded that patients receiving PPIs were at greater risk for C. difficile diarrhea.9 Given these concerns associated with acid-suppressive therapy, at-risk patients should be identified.  Community-acquired pneumonia is a danger for those who are generally at risk for infection.10  At risk groups include those with asthma, chronic obstructive pulmonary disease, children, the elderly, and those who are immunocompromised.11  In these at risk groups, patients needing acid-suppressive therapy may benefit from sucralfate (Carafate) which does not appear to affect gastric acid concentration.12 Evidence presented in this study suggests that patients should be treated with acid-suppressing drugs only when necessary and at the lowest effective dose [Evidence level B, epidemiologic study, clinical cohort study].2    Users of this document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document.  Our editors have researched the information with input from experts, government agencies, and national organizations.  Information and Internet links in this article were current as of the date of publication.  Levels of Evidence In accordance with the trend towards Evidence-Based Medicine, we are citing the LEVEL OF EVIDENCE for the statements we publish.  Level Definition A High-quality randomized controlled trial (RCT)  High-quality meta-analysis (quantitative systematic review) B Nonrandomized clinical trial  Nonquantitative systematic review  Lower quality RCT  Clinical cohort study  Case-control study  Historical control  Epidemiologic study C Consensus  Expert opinion D Anecdotal evidence In vitro or animal study Adapted from Siwek J, et al.  How to write an evidence-based clinical review article.  Am Fam Physician 2002;65:251-8.  References 1. Gregor JC.  Acid suppression and pneumonia: a clinical indication for rational prescribing.  JAMA 2004;292:2012-13. 2. Laheij RJ, Sturkenboom MC, Hassing R, et al.  Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs.  JAMA 2004;292:1955-60. 3. Williams C.  Occurrence and significance of gastric colonization during acid-inhibition therapy.  Best Pract Res Clin Gastroenterol 2001;15:511-21. 4. Thorens J, Froehlich F, Schwizer W, et al.  Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a (Detail-Document #201207:  Page 3 of 3)  prospective randomized double blind study.  Gut 1996;39:54-9. 5. Hayase Y, Tobita K, Sato H.  Detection of type B influenza virus genes from biopsied gastric mucosa.  J Gastroenterol 2002;37:101-5. 6. Brummer RT, Stockbrugger RW.  Effect of nizatidine 300 mg at night and omeprazole 20 mg in the morning on 24-hour intragastric pH and bacterial  overgrowth in patients with acute duodenal ulcer.  Dig Dis Sci 1996;41:2048-54. 7. Inglis TJ, Sherratt MJ, Sproat LJ, et al.  Gastroduodenal dysfunction and bacterial colonisation of the ventilated lung.  Lancet 1993;341:911-3. 8. Laheij RJ, VanIjzendoorn MC, Janssen MJ, Jansen JB.  Gastric acid-suppressive therapy and community-acquired respiratory infections.  Aliment Pharmacol Ther 2003;18:847-51. 9. Dial S, Alrasadi K, Manoukian C, et al.  Risk of Clostridium difficile diarrhea in hospital in-patients prescribed proton pump inhibitors: cohort and case-control studies.  CMAJ 2004;171:33-8. 10. Bartlett JG, Mundy LM.  Community-acquired pneumonia.  N Engl J Med 1995;333:1618-24. 11. Fine MJ, Smith MA, Carson CA, et al.  Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis.  JAMA 1996;275:134-41. 12. Collard HR Saint, S, Matthay, MA.  Prevention of ventilator-associated pneumonia: an evidence-based systematic review.  Ann Intern Med 2003;138:494-501.  Cite this Detail-Document as follows:  Community-acquired pneumonia risk with acid-suppressive drugs.  Pharmacist’s Letter/Prescriber’s Letter2004;20(12):201207.  ®  The most practical knowledge in the least time… ®  3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright © 2004 by Therapeutic Research Center  Subscribers to Pharmacist’s Letter and Prescriber’s Letter can get Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com or www.prescribersletter.com 

Community-acquired pneumonia risk with acid-suppressive drugs

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Community-acquired pneumonia risk with acid-suppressive drugs

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