Among adults suspected of having community-acquired pneumonia who are hospitalized in non-ICU wards, empirical treatment with beta-lactam monotherapy is noninferior both to beta-lactam plus macrolide combination therapy and to fluoroquinolone monotherapy, according to a report published online April 2 in the New England Journal of Medicine.
Current guidelines recommend the latter two approaches, which has caused a widespread increase in the use of macrolides and fluoroquinolones – and in turn has increased antibiotic resistance.
Moreover, “the evidence in support of these recommendations is limited,” said Dr. Douwe F. Postma of the Julius Center for Health Sciences and Primary Care and the University of Utrecht (the Netherlands), and his associates.
To compare outcomes among the three treatment strategies, Dr. Postma and his colleagues conducted the Community-Acquired Pneumonia – Study on the Initial Treatment with Antibiotics of Lower Respiratory Tract Infections (CAP-START) trial in seven Dutch hospitals during a 2.5-year period (N. Engl. J. Med. 2015;372:1312-23).
The cluster-randomized, crossover study called for participating hospitals to rotate using each of the empirical strategies during consecutive 4-month periods for all eligible patients. A total of 656 patients were assigned to receive beta-lactam monotherapy, 739 to receive beta-lactam plus macrolide combination therapy, and 888 to receive fluoroquinolone monotherapy. The median patient age was 70 years.
The primary outcome – all-cause mortality at 90 days after admission – favored beta-lactam monotherapy over the combination therapy by an absolute difference in adjusted risk of death of 1.9 percentage points, and favored beta-lactam monotherapy over fluoroquinolone monotherapy by less than 1 percentage point. That demonstrated the noninferiority of beta-lactam monotherapy, the researchers noted.
Both secondary outcomes – length of hospital stay and treatment-related complications – also were similar among the three study groups, the investigators added.
That noninferiority was confirmed in several further analyses of the data, including a sensitivity analysis restricted only to patients who had radiologically confirmed CAP and another sensitivity analysis that examined 30-day all-cause mortality.
“These findings, together with the slightly longer length of hospital stay with [macrolide monotherapy], reported associations with the development of resistance, and possible increased risk of cardiac events, indicate that the addition of macrolides for empirical treatment of CAP should be reconsidered,” Dr. Postma and his associates said.
The Netherlands Organization for Health Research and Development supported the study. Dr. Postma and his associates reported having no financial disclosures.