Reference: Lancet. 2021 Mar 27;397(10280):1195-1203
Bacterial pneumonia is a scourge for very young, very old, and other vulnerable people. However, most healthy older children and younger adults eventually recover from community-acquired pneumonia. So what should we do with adults who are vulnerable or sick enough to be hospitalized but improve after a few days of antibiotics? Do we send them home without a prescription, or continue antibiotics to ensure a complete recovery? Many of us were taught to give a few more days of oral antibiotics on discharge to prevent relapse.
Researchers in France wondered if this was necessary, and designed a randomized, double-blind, placebo-controlled trial to address this concern. They enrolled 310 patients hospitalized with uncomplicated pneumonia who had responded to ≥ 72 hours of a beta-lactam antibiotic and were either ready or almost ready for discharge. Upon admission to the hospital, about one third of patients were classified by the pneumonia severity index (PSI score) as risk class 2, a quarter were class 3, and the remainder were considered high-risk category 4 or 5. After three days of inpatient therapy and demonstrated improvement, patients were randomly given five more days of either oral amoxicillin-clavulanic acid 500/62.5 mg or placebo three times daily and usually discharged that day. Results showed that most patients (70-75%) recovered uneventfully without significant differences in the primary outcome of cure at 15 days or secondary outcomes such as mortality or adverse events. The authors examined the data using both intention-to-treat (ITT) and per-protocol (PP) analyses, and the results were concordant. Subgroup analyses in patients in the higher risk categories predictably showed worse outcomes, again concordant.
Iatrogenic harm, cost, and drug class-specific concerns such as antibiotic resistance are factors in the increasing prevalence of non-inferiority trials. One problem with non-inferiority trials in general is the “dilution effect” which may occur if participant adherence is low. The similarity in PP and ITT analyses suggests this wasn’t the case here. Our one critique is the relatively large (about one third) percentage of patients in PSI risk class 2. Guidelines acknowledge that clinical severity scores should not be the only factor in hospital admission for pneumonia. But sub-group analysis from this study demonstrates that across the board, a low PSI score at admission predicts cure at 15 days. This study should be repeated in group of patients who are exclusively or predominantly in PSI risk classes 4 and 5, patients who would be expected to demonstrate benefit from prolonged antibiotics if they are helpful.
For more information, see the topic Antibiotics for Adult Inpatients With Community-acquired Pneumonia in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency, and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.