MedicalResearch.com Interview with:
Dr. Nicolas Garin MD
Division of General Internal Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
Division of Internal Medicine, Hôpital Riviera-Chablais, Monthey, Switzerland
Medical Research: What are the main findings of the study?
Dr. Garin: Empiric treatment with a betalactam drug (monotherapy) was not equivalent to the combination of a betalactam and a macrolide in patients hospitalized for moderate severity pneumonia (proportion of patients not having reached clinical stability at day 7 was 41.2 % in the monotherapy vs. 33.6 % in the combination therapy arm, between arm difference 7.6 %). This occurred despite systematic search for Legionella infection in the monotherapy arm. There was no difference in early or late mortality, but patients in the monotherapy arm were more frequently readmitted. Patients with higher severity of disease (in PSI category IV, or with a CURB-65 score higher than 1) seemed to benefit from combination therapy (HR 0.81 for the primary outcome of clinical instability at day 7), although it was statistically not significant. There was no difference in the primary outcome for patients in PSI category I to III.
Medical Research: What was most surprising about the results?
Dr. Garin: Previous meta-analysis of randomized-controlled trials did not find any difference between empiric treatment with or without systematic coverage of so-called “atypical pathogens ” (i.e Legionella sp., Mycoplasma pneumoniae and Chlamydia pneumoniae). We were surprised to find less patients reaching clinical stability at day 7 in the monotherapy arm. This difference was particularly striking for patients with higher severity of disease, and persisted after excluding patients with proven infection by an atypical pathogen. Our results can be explained either by the lack of coverage of atypical pathogens not detected by current testing, or by a non-antibiotic, anti-inflammatory effect of the macrolide.
Medical Research: What should clinicians and patients take away from your report?
Dr. Garin: Pending more investigations, patients hospitalized for community-acquired pneumonia and in PSI category IV or more, or with a CURB-65 score of 2 or more, should be treated with a betalactam and a macrolide.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Garin: Our results should be replicated in other geographical contexts. Larger studies should test if the combination therapy has an impact on “hard” endpoints (early and late mortality). We should explore the cause of the apparent superiority of the combination therapy : coverage of undetected atypical pathogens, or modulation of the host inflammatory response?