Usefulness of β-lactam and Macrolide Combination Therapy for Treating Community-acquired Pneumonia Patients Hospitalized in the Intensive Care Unit: Propensity Score Analysis of a Prospective Cohort Study

Background: Previous studies reported that β-lactam and macrolide combination therapy significantly improved outcomes for patients with severe community-acquired pneumonia hospitalized in the intensive care unit (ICU) compared with a non-macrolide regimen. However, whether β-lactam and macrolide therapy truly reduces mortality is controversial, because no randomized, controlled trials have been conducted. The aim of the present study was to evaluate the usefulness of β-lactam and macrolide combination therapy for severe community-acquired pneumonia patients hospitalized in the ICU compared with a non-macrolide β-lactam-containing regimen.Methods: A prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized severe community-acquired pneumonia patients admitted to the ICU within 24 hours between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score.Results: A total of 78 patients were included. There were 48 patients in the non-macrolide-containing β-lactam therapy group, including β-lactam monotherapy and β-lactam and non-macrolide-containing combination therapy, and 30 patients in the macrolide combination therapy group. β-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P=0.015) and 14-day mortality (6.7% vs. 31.3%; P=0.020), but not ICU mortality (10% vs 27.1%, P=0.08) compared with non-macrolide-containing β-lactam therapy. After adjusting by inverse probability of treatment weighting, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09-0.96; P=0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04-0.92; P=0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08-1.36; P=0.13).Conclusions: Combination therapy with β-lactam and macrolides significantly improved the prognosis of severe community-acquired pneumonia patients hospitalized in the ICU compared with a non-macrolide-containing β-lactam regimen on propensity score analysis.Trial registration: UMIN Clinical Trials Registry, UMIN000004353. Registered on 7 October 2010