Work

Sequential Administration of Beta-Lactams and Macrolides on the Outcomes of Hospitalized Patients With Community-Acquired Pneumonia: Results From the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study

Year: 2016

Type: article

Abstract: Background. Guidelines for CAP recommend administration of beta-lactam plus macrolides since this combination decreases mortality. Explanations for decreased mortality include: 1) macrolides are effective against atypical pathogens and 2) macrolides act as anti-inflammatory agents. In patients with meningitis, the anti-inflammatory agent (steroids) are administered before the use of beta-lactam antibiotics to improve clinical outcomes. Data on the clinical outcomes of patients with CAP are lacking regarding the effect of macrolides when given before or after beta-lactams. The objective of this study was to compare clinical outcomes when macrolides are used before or after administration of beta-lactams. Methods. This was a secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study database. Patients receiving a combination of beta-lactams plus macrolides for empiric therapy were included. Patients given beta-lactams and macrolides within 1 hour or more than 24 hours apart were excluded. TCS and LOS were analyzed with the Kaplan-Meier method, and log-rank tests applied to evaluate differences between both groups. To define the adjusted association between macrolide versus beta-lactam timing on the risk of in-hospital mortality, a log-binomial regression model was used. Results. A total of 555 patients were included, 63 with a macrolide first and 492 with a beta-lactam first. Median (IQR) time to clinical stability was 4 days (2.5) for patients receiving a macrolide first and 5 days (5) for patients receiving a beta-lactam first (P < 0.001). Median (IQR) time to clinical stability was 5 days (5) for patients receiving a macrolide first and 8 days (7) for patients receiving a beta-lactam first (P < 0.001). The adjusted percent in-hospital mortality was 1% for patients receiving a macrolide first and 8% for patients receiving a beta-lactam first (P = 0.158). Conclusion. These data suggest that, although not statistically significant, there is a clinically relevant decrease in in-hospital mortality if a macrolide is given before a beta-lactam. Since macrolides may decrease mortality only when given prior to beta-lactam antibiotics, their activity is likely due to anti-inflammatory effects and prevention of bacterial lysis as opposed to coverage of atypical pathogens. Disclosures. All authors: No reported disclosures

Source: Open Forum Infectious Diseases

DOI: 10.1093/ofid/ofw172.939