TOPLINE:

Among patients hospitalized with community-acquired pneumonia (CAP), the addition of azithromycin to a beta-lactam antibiotic was not associated with improved clinical outcomes compared with beta-lactam monotherapy. Similar findings were observed in patients with high disease severity, as assessed by Sequential Organ Failure Assessment (SOFA) score ≥ 2.

METHODOLOGY:

• Researchers conducted a retrospective matched cohort study to evaluate whether adding azithromycin to beta-lactam monotherapy vs beta-lactam monotherapy alone improved clinical outcomes in hospitalized patients with CAP.
• They included 246 patients with a primary diagnosis of CAP, of whom 121 (median age, 84 years; 50% men) received beta-lactam monotherapy and 125 (median age, 77 years; 78% men) received beta-lactam monotherapy with azithromycin between January and December 2023 in Spain.
• Beta-lactam monotherapy included intravenous ceftriaxone 2 g every 24 hours, intravenous amoxicillin-clavulanate 1 g every 8 hours, or intravenous piperacillin-tazobactam 4 g every 8 hours; combination therapy included beta-lactam plus azithromycin, with at least three doses of azithromycin 500 mg daily administered intravenously or orally.
• The primary objective was to compare the clinical efficacy of beta-lactam plus azithromycin vs beta-lactam monotherapy. Clinical efficacy was assessed at 72-96 hours after admission using a composite of no oxygen requirement, no fever, and at least a 50% reduction in C-reactive protein and/or procalcitonin levels.
• The secondary outcomes included changes in the duration of antibiotic treatment and length of hospital stay, 30-day mortality, the need for noninvasive ventilation, and readmission within 90 days after completion of therapy.

TAKEAWAY:

• Clinical efficacy did not differ significantly between the beta-lactam monotherapy and combination therapy groups (65% vs 62%), with no differences being observed in oxygen requirement, persistence of fever, or reduction in biomarker levels.
• The 90-day readmission rate (P = .021) was higher with monotherapy, but the duration of beta-lactam treatment was longer with combination therapy (P = .019). No significant differences were observed in the other secondary outcomes.
• The SOFA score was similar between groups at baseline, and a SOFA score ≥ 2 was independently associated with a 50% decline in clinical efficacy (adjusted odds ratio, 0.5; P = .026).
• Among patients with a SOFA score ≥ 2, no clinically meaningful differences were observed in clinical efficacy between the monotherapy and combination therapy groups (59% vs 53%), with no differences observed in the secondary outcomes.

IN PRACTICE:

“Our findings suggest that routine combination therapy with a macrolide and a beta-lactam may not be necessary for hospitalized patients with CAP. Furthermore, optimizing antibiotic duration remains an essential target for antimicrobial stewardship interventions,” the authors wrote.

SOURCE:

The study was led by Ilona Zhygalova Zhygalova, Complexo Hospitalario Universitario de Vigo, Vigo, Spain. It was published online on May 15, 2026, in Journal of Antimicrobial Chemotherapy.

LIMITATIONS:

The study’s retrospective, single‑center design and modest sample size limited the results’ generalizability and precluded establishing causal inferences. The institutional empirical protocol recommended adding azithromycin for severe infections, which may have introduced selection bias. The requirement of at least 3 days of azithromycin may have introduced survivor bias.

DISCLOSURES:

No specific funding sources were reported for the study. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.