DUAL ANTIBIOTIC THERAPY FOR MODERATE SEVERE PNEUMONIA

NEW YORK (Reuters Health) - Dual antibiotic therapy is needed for patients hospitalized with moderately severe community-acquired pneumonia (CAP), suggests a randomized controlled trial.

The study team tried and failed to demonstrate noninferiority of a beta-lactam alone over a beta-lactam-macrolide combination in this patient population.

There is ongoing debate about optimal antibiotic therapy for patients hospitalized with CAP. North American guidelines currently advise dual antibiotic therapy that covers typical and atypical bacterial pathogens for all patients hospitalized for CAP (i.e., beta-lactam plus macrolide or fluoroquinolone monotherapy), while British guidelines reserve such therapy for moderately to severely ill patients.

Dr. Nicolas Garin, from Hopital Riviera-Chablais, Switzerland, and colleagues conducted an open-label, multicenter noninferiority trial of 580 patients admitted to six hospitals in Switzerland for moderately severe CAP. Patients were randomly allocated to receive monotherapy with a beta-lactam or dual therapy with a beta-lactam and a macrolide. Legionella pneumophila infection was diagnosed using urinary antigen testing, and macrolide therapy was added for patients in the monotherapy arm testing positive.

On hospital day 7, more patients in the monotherapy arm compared with the dual therapy arm had not reached clinical stability (the primary outcome: 41.3% vs 33.4%; p=0.07). "The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%," the authors say.

In subgroup analyses, patients infected with atypical pathogens (hazard ratio, 0.33) or with Pneumonia Severity Index (PSI) category IV (HR 0.81) were less likely to reach clinical stability with one antibiotic. Outcomes were similar in patients not infected with atypical pathogens (HR 0.99) or with PSI category I to III pneumonia (HR 1.06).

A smaller proportion of patients treated with dual therapy were readmitted at 30 days (3.1% vs 7.9%; p=0.01), but none of the other secondary outcomes (mortality, ICU admission, complications, length of stay or pneumonia recurrence within 90 days) varied between the treatment arms.

In email to Reuters Health, Dr. Garin said, "I think the take home message is: for empiric treatment of CAP, beta-lactam monotherapy should be reserved for patients with PSI class I to III severity (or CURB-65 score 0-1). A macrolide should be combined with a beta-lactam for patients in PSI class IV or V or with a CURB-65 score > 1."

The study was published online October 6 in JAMA Internal Medicine.

In an editorial, Dr. Jonathan Lee and Dr. Michael Fine of the University of Pittsburgh School of Medicine in Pennsylvania say the evidence from this trial "pushes the pendulum further in favor of antibiotic therapy covering atypical and typical bacterial pathogens for patients hospitalized for CAP. Lessons learned from its design and results should inform future trials required to definitively settle this debate."

Until then, they conclude, "dual therapy should remain the recommended treatment for patients hospitalized for CAP."

SOURCES: http://bit.ly/1xWcPxI, http://bit.ly/10Fgp1F

JAMA Intern Med 2014.