In the Journals

Beta-lactam monotherapy failed to show noninferiority for CAP

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October 6, 2014

Researchers were unable to demonstrate noninferiority of beta-lactam monotherapy compared with beta-lactam/macrolide combination therapy for moderately severe community-acquired pneumonia, according to data published in JAMA Internal Medicine.

“There was a nonsignificant trend toward superiority of combination therapy, which could represent a chance finding or true superiority that was not significant because of insufficient power,” Nicolas Garin, MD, of the division of internal medicine, Hôpital Riviera-Chablais, Monthey, Switzerland, and colleagues wrote. “Although most secondary outcomes did not differ between the two treatment arms, patients in the monotherapy arm had more readmissions within 30 days. This finding might also point toward a superiority of combination therapy.”

The researchers conducted the open label, randomized, noninferiority trial from Jan. 13, 2009 to Jan. 31, 2013. The study included 580 immunocompetent adults being treated for moderately severe community-acquired pneumonia at six hospitals in Switzerland. The patients were randomly assigned to monotherapy with a beta-lactam or combination therapy with a beta-lactam and a macrolide. Patients in the monotherapy arm who had a Legionella pneumophila antigen were given a macrolide (n=12).

After 7 days of treatment, 41.2% of patients in the monotherapy arm had not yet reached clinical stability, compared with 33.6% of patients in the combination arm (P=.07). The upper limit of the 90% confidence interval was 13%, above the predefined noninferiority boundary of 8%. There were no survival differences between the two groups. There were no differences in secondary outcomes, with the exception of rates of readmission 30 days after discharge: 7.9% in the monotherapy arm vs. 3.1% for the combination therapy (P=.01).

In a subgroup analysis, combination therapy was significantly superior for patients with atypical pathogens, and patients with more severe pneumonia demonstrated a trend toward better outcome with combination therapy. Patients not infected with atypical pathogens, or patients with less severe pneumonia, had similar outcomes in both arms.

Macrolide use is associated with possible adverse cardiovascular events and cardiovascular death,” the researchers wrote. “This association is relevant because pneumonia affects predominantly older people, who are at increased risk of heart disease, and pneumonia itself is a trigger for adverse events. On the other hand, macrolides cover atypical pathogens and might affect favorably the host inflammatory response through nonantibiotic effects. Consequently, potential advantages of combination therapy should be balanced with a potential increased risk of adverse cardiac events and increased selection of resistant pathogens.”

Disclosure: The researchers report no relevant disclosures.

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