The comparison of outcomes in community-acquired pneumonia treated azithromycin or doxycycline in combination with beta-lactams: A cohort study

Background and aim While both azithromycin (AZM) and doxycycline (DOX) are recommended as adjuncts to beta-lactam (BL) therapy for hospitalized community-acquired pneumonia (CAP) patients, there is insufficient evidence to guide the selection. We aimed to compare the outcomes of CAP patients treated with AZM or DOX in combination with BL agents. <bold>Methods:</bold> We evaluated CAP patients admitted to Mayo Clinic hospitals from May 2018 to September 2022 who received either AZM or DOX in combination with a BL. Those who received both AZM or DOX or were on either agent prior to admission as chronic therapy were excluded. The primary outcome was in-hospital mortality. Secondary outcomes were 90-day survival, hospital-free days (HFD), and acute kidney injury (AKI). Multivariable analyses adjusted for age, sex, sepsis, and comorbidities. <bold>Results:</bold> Of the 13933 patients screened, 8533 were included (5839 for AZM and 2694 for DOX). Adjusting for covariates, in-hospital mortality was lower in the AZM group compared to DOX (adjusted odds ratio [aOR] 0.76; 95% confidence interval [CI], 0.61-0.96). AZM patients had more HFD than DOX patients (adjusted estimate=1.04; 95%CI, 0.67, 1.42). In univariate comparisons, AZM was associated with improved 90-day survival compared to DOX (hazard ratio [HR] 0.8; 95% CI, 0.71, 0.9). After adjustment for covariates 90-day survival was not different (adjusted HR 0.9; 95% CI, 0.79, 1.04). AZM was independently associated with a lower risk of AKI than DOX (aOR 0.77; 95% CI, 0.61, 0.96). <bold>Conclusion:</bold> Our results suggest a potential association between improved outcomes in CAP patients treated with AZM compared to DOX when combined with BL.