ORAL 5-DAY LEFAMULIN FOR OUTPATIENT MANAGEMENT OF COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA: POST-HOC ANALYSIS OF THE LEFAMULIN EVALUATION AGAINST PNEUMONIA (LEAP) 2 TRIAL

Background: Safe and effective oral antibiotics are needed for outpatient management of moderate to severe community-acquired bacterial pneumonia (CABP). Objective: We describe a post-hoc analysis of adults with CABP managed as outpatients from the Lefamulin Evaluation Against Pneumonia (LEAP) 2 double-blind, noninferiority, phase 3 clinical trial. Methods: LEAP 2 compared the efficacy and safety of oral lefamulin 600 mg every 12 h (5 days) vs. oral moxifloxacin 400 mg every 24 h (7 days) in adults (inpatients and outpatients) with Pneumonia Outcomes Research Team (PORT) risk classes II.IV. Results: Overall, 41% (151 of 368) of patients receiving lefamulin and 43% (159 of 368) of patients receiving moxifloxacin started treatment as outpatients- 44% and 40%, respectively, were PORT risk class III/IV, and 21% in both groups had CURB-65 scores of 2.3. Early clinical response (at 96 +/- 24 h) and investigator assessment of clinical response success rates at test of cure (5.10 days after last study drug dose) were high and similar in both groups among all (lefamulin, 91% vs. moxifloxacin, 89.90%), PORTrisk class III/ IV (89.91% vs. 88.91%), and CURB-65 score 2.3 (87.90% vs. 82.88%) outpatients. Few outpatients (lefamulin, 2.6%; moxifloxacin, 2.5%) discontinued the study drug because of treatment-emergent adverse events (TEAEs). No outpatient in the lefamulin group was hospitalized for a TEAE, compared with 5 patients (3%), including two deaths, in the moxifloxacin group. Conclusions: These data suggest that 5 days of oral lefamulin can be given in lieu of fluoroquinolones for outpatient treatment of adults with CABP and PORT risk class III/IV or CURB-65 scores of 2.3. (C) 2021 The Author(s). Published by Elsevier Inc.