Risk of Community-Acquired Pneumonia and Use of Gastric Acid-Suppressive Drugs
Abstract & Commentary
Synopsis: Current use of gastric acid-suppressive therapy was associated with an increased risk of community-acquired pneumonia.
Source: Laheij RF, et al. Risk of Community-Acquired Pneumonia and Use of Gastric Acid Suppressive Drugs. JAMA. 2004;292:1955-1960.
In a survey of 365,000 records of patients followed by general practitioners in Holland for at least 1 year during a 7-year period, 5551 incident cases of pneumonia developed. Users of acid suppression, particularly proton pump inhibitors (PPIs), had a 4.5 fold increased unadjusted risk of pneumonia, compared to untreated controls.
Laheij and colleagues believe that this increased risk can be attributed to the loss of the protective acid milieu of the stomach that normally serves as a barrier to pathogens. Current PPI users were at more risk than patients who had previously discontinued PPI use, and there was no increased risk of pneumonia for those with a distant past history of use of acid-inhibiting drugs. Histamine-2 receptor antagonists (H2RAs) appeared to be associated with a similar unadjusted excess risk of pneumonia to that seen with PPIs. However, the number of patients using various H2RAs and various H2RA doses was too small to allow discrimination of risks beyond those for the entire population of H2RA recipients. Higher PPI doses seemed to produce a further elevation of pneumonia risk vs conventional daily doses. Laheij et al seem quite confident in the reliability of these results from such a large population in a country where follow-up of patients is virtually guaranteed by the national health system.
Comment by Malcolm Robinson, MD, FACP, FACG
This is not the first time that this attribution of pneumonia risk to use of acid suppressing drugs has been made. In an accompanying JAMA editorial, the actual described risk is placed at 1 case per 100 patient years (about the same as the risk of GI hemorrhage from use of NSAIDs). Nevertheless, the results of this study should not be accepted without reservation. For example, it is likely that much of the use of antisecretory medication is directed toward gastroesophageal reflux disease. GERD itself may represent an important contributor to the pathogenesis of pneumonia (eg, by aspiration). If so, the association of drugs used for treatment might be entirely spurious. Only a prospective study would sort this out, and such a study is quite unlikely to be done. In a marketing flurry based on competition between sucralfate and ranitidine, there was an attempt to demonstrate that ranitidine was associated with nosocomial pneumonia in the hospital. This concept was thoroughly discredited at that time. H2RAs do not produce achlorhydria or even profound hypochlorhydria, and even the much more potent PPIs do not eliminate stomach acid. Although there is a remote possibility that acid suppression may in some cases tilt the balance toward bacterial overgrowth in the stomach, this effect is likely to be counterbalanced by the dramatic decrements in gastric volume that also are associated with antisecretory agents (particularly PPIs). I am sure that we have not heard the last word in this area, but I would urge physicians to realize that the amazing efficacy of currently available H2RAs and PPIs should continue to be made available to all patients with diagnoses that demand acid-suppressive therapy.
Dr. Robinson, MD, FACP, FACG, is Medical Director at the Oklahoma Foundation for Digestive Research and Clinical Professor of Medicine at the University of Oklahoma College of Medicine.