Additional effect of azithromycin over \u03b2-lactam alone for severe community-acquired pneumonia-associated acute respiratory distress syndrome: a retrospective cohort study

Jun Suzuki,Shuji Hatakeyama,Teppei Sasahara,Hiroki Matsui,Hideo Yasunaga,Yusuke Sasabuchi,Toshiyuki Yamada,Yuji Morisawa,Kiyohide Fushimi

doi:10.1186/s41479-021-00093-8

Abstract

BackgroundCommunity-acquired pneumonia (CAP) is the most common cause of acute respiratory distress syndrome (ARDS). Although previous studies have suggested that macrolide therapy is beneficial for ARDS, its benefit for severe CAP-associated ARDS remains uncertain. Previous studies were limited in that they had a small sample size and included patients with non-pulmonary ARDS and those with pulmonary ARDS. This study aimed to investigate the additional effect of azithromycin when used with β-lactam compared with the effect of β-lactam alone in mechanically ventilated patients with CAP-associated ARDS.MethodsWe identified mechanically ventilated patients with CAP-associated ARDS between July 2010 and March 2015 using data in the Diagnosis Procedure Combination database, a Japanese nationwide inpatient database. We performed propensity score matching analysis to assess 28-day mortality and in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS who received β-lactam with and without azithromycin within hospital 2 days after admission. The inverse probability of treatment weighting analysis was also conducted.ResultsEligible patients (n = 1257) were divided into the azithromycin group (n = 226) and the control group (n = 1031). The one-to-four propensity score matching analysis included 139 azithromycin users and 556 non-users. No significant difference was observed between the groups with respect to 28-day mortality (34.5% vs. 37.6%, p = 0.556) or in-hospital mortality (46.0% vs. 49.1%, p = 0.569). The inverse probability of treatment weighting analysis showed similar results.ConclusionsCompared with treatment with β-lactam alone, treatment with azithromycin plus β-lactam had no significant additional effect on 28-day mortality or in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS. To the best of our knowledge, this study is the first to determine the effect of azithromycin in mechanically ventilated patients with CAP-associated ARDS.

Highlights

Severe community-acquired pneumonia (CAP) is the most common cause of acute respiratory distress syndrome (ARDS) [1, 2] and death [3, 4] in critically ill patients
Patient selection In this retrospective cohort study, we identified severe Community-acquired pneumonia (CAP)-associated ARDS, which was defined as mechanically ventilated patients who were diagnosed with sepsis and pneumonia and received β-lactam within hospital 2 days after admission between July 2010 and March 2015
A total of 1257 patients with severe CAP-associated ARDS during the 57-month study period were identified in the Diagnosis Procedure Combination (DPC) database

Summary

Introduction

Severe community-acquired pneumonia (CAP) is the most common cause of ARDS [1, 2] and death [3, 4] in critically ill patients. Clinical and experimental studies have shown immunomodulatory effects of macrolides, such as reduction in cytokine production, neutrophil accumulation in the airways, mucus hypersecretion, and biofilm formation, as well as the acceleration of neutrophil apoptosis [8]. These effects may reduce the risk of mortality in patients with severe pneumonia [9], and several guidelines have recommended azithromycin combined with β-lactam for patients with severe CAP [6, 7].

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