Single Antibiotic as Good as Combination for Pneumonia

Marcia Frellick

April 02, 2015

For patients admitted to non–intensive care unit (ICU) wards who have suspected community-acquired pneumonia (CAP), a strategy of empirical treatment with a beta-lactam antibiotic alone was found to be just as good as the currently recommended combination therapy.

Specifically, the single-treatment strategy, which allowed for deviations for medical reasons, had results similar to those of the usual beta-lactam–macrolide combination therapy or fluoroquinolone monotherapy, in terms of 90-day all-cause mortality. Also, the beta-lactam antibiotic alone did not lengthen hospital stays or result in more complications. Results were published in the April 2 issue of the New England Journal of Medicine.

Experts continue to debate optimal antibiotic therapy for patients hospitalized with CAP, a leading cause of hospitalization and death worldwide. North American guidelines currently advise the dual-antibiotic therapy (beta-lactam plus macrolide or fluoroquinolone monotherapy) that covers typical and atypical bacterial pathogens for all patients. However, the guidelines, which some experts say are based on scant evidence, have increased the use of macrolides and fluoroquinolones, despite their association with antibiotic resistance.

In contrast, British guidelines reserve combination therapy for the moderately to severely ill.

Therefore, Douwe Postma, MD, from the University Medical Center, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands, and colleagues assessed whether a strategy of preferred empirical treatment with beta-lactam monotherapy is noninferior to either the preferred beta-lactam–macrolide combination therapy or preferred fluoroquinolone monotherapy, measured by 90-day all-cause mortality among adults with clinically suspected CAP who are admitted to non-ICU wards.

The researchers designed the study so that clinicians were allowed to change treatment for an individual patient from the assigned therapy when medical conditions called for it, so as not to compromise care.

The absolute difference in the adjusted risk for death between the beta-lactam strategy and the beta-lactam–macrolide combo strategy was 1.9 percentage points (90% confidence interval [CI], −0.6 to 4.4 percentage points) in favor of the monotherapy strategy. The difference between the beta-lactam strategy and the fluoroquinolone was −0.6 percentage points (90% CI, −2.8 to 1.9 percentage points) in favor of the fluoroquinolone.

Both differences fell within the prespecified boundary of 3 percentage points, indicating that the monotherapy regimens were not inferior to the combination regimens.

The median length of stay was 6 days for all strategies, and the median duration of intravenous treatment was 3 days during the fluoroquinolone strategy periods and 4 days with the other strategies. Proportions of patients whose treatment started with oral antibiotics were 27% during the fluoroquinolone strategy periods and 13% and 10% during the beta-lactam and beta-lactam–macrolide strategy periods, respectively.

Given those findings, the authors recommend that the addition of macrolide should be reconsidered for empirical treatment of CAP in non-ICU patients.

Funding was provided by the Netherlands Organization for Health Research and Development. The authors have disclosed no relevant financial relationships.

N Engl J Med. 2015;372:1312-1323. Abstract

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