Doxycycline vs. macrolides in combination with a β-lactam antibiotic for the treatment of community-acquired pneumonia in inpatients

Background: Hospitalized patients with non-severe community-acquired pneumonia (CAP) are treated with a beta-lactam plus either a macrolide or doxycycline. Limited data exist on the effectiveness of the latter combination. Therefore, we aimed to compare the combination of doxycycline vs. macrolide when either is combined with a beta-lactam from effectiveness and safety perspectives. Methods: This was a retrospective cohort study in CAP inpatients between December 2013 and November 2020. Patients were divided into BL-D (beta-lactam plus doxycycline) and BL-M (beta-lactam plus a macrolide [azithromycin or clarithromycin]) groups. The primary endpoint was time to clinical stability. Secondary endpoints included length of stay (LOS) and in-hospital mortality. Results: Of 197 patients included, 57 were in the BL-D arm and 140 were in the BL-M arm. Patients were similar at baseline, except for the presence of leukocytosis, risk factors for drug resistance, and duration of therapy (P < 0.05 for all comparisons). No difference in clinical cure rate was observed (94.7% vs. 91.4%; P = 0.43). Time to clinical stability and LOS were similar in both groups at 4 (P = 0.82) and 7 days (P = 0.62), respectively. While only three patients died, only one (from the BL-M group) was due to sepsis. Liver enzymes elevation was more prominent in the BL-M group (21.4% vs. 5.3%; P = 0.01). A subgroup analysis showed shorter time to clinical stability with clarithromycin but higher cure rates with azithromycin. Conclusions: Data on doxycycline use with a beta-lactam are scarce. Our study showed that such regimen was comparable in effectiveness to regimens involving macrolides with a better safety profile.

Automated summary

This study compared the effectiveness and safety of a combination of doxycycline with a beta-lactam and a combination of a macrolide with a beta-lactam in the treatment of non-severe community-acquired pneumonia. The results showed that there was no significant difference in clinical cure rate, time to clinical stability, and length of stay between the two groups. However, the combination of doxycycline with a beta-lactam had a better safety profile.