Association Between the Order of Macrolide and Cephalosporin Treatment and Outcomes of Pneumonia

Background. Many patients hospitalized with pneumonia are treated with combination macrolide/cephalosporin therapy. Macrolides have immunomodulatory effects and do not directly cause bacterial lysis. These effects suggest the possibility that initial treatment with a macrolide before a cephalosporin could improve patient outcomes by preventing the inflammatory response to rapid bacterial lysis that can be caused by cephalosporin treatment. This study explores whether initial treatment for pneumonia with a macrolide before a cephalosporin is associated with better patient outcomes than treatment with a cephalosporin before a macrolide. Methods. This is a retrospective cohort study using a clinically rich database derived from electronic health records of 71 hospitals. We compared outcomes for pneumonia patients who received intravenous treatment with a macrolide at least 1 hour before a cephalosporin, versus patients who received a cephalosporin at least 1 hour before a macrolide. Propensity matching was performed for 527 patients in each group. Results. Among the propensity-matched cohorts, for the macrolide first group, in-hospital mortality was 4.2% vs 5.5% for the cephalosporin first group (P = .31), combined in-hospital mortality/hospice discharge was 6.3% vs 9.3% (P = .06), median hospital length of stay was 101.5 hours vs 109.5 hours (P = .09), and 30-day readmission was 12.9% vs 10.6% (P = .27). Conclusions. Treatment of pneumonia with a macrolide before a cephalosporin was not associated with significantly improved outcomes when compared with treatment with a cephalosporin first; however, the lower rate of mortality/discharge to hospice and the large confidence intervals allow for the possibility of a clinically significant benefit.