663. Efficacy and Safety of Lefamulin (LEF) vs. Moxifloxacin (MOX) for Legionella pneumophila (LP) in Patients with Community-Acquired Bacterial Pneumonia (CABP): Pooled Results From the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Clinical Trials

Abstract

Background LP is associated with severe CABP, rapid onset, and high morbidity/mortality. Poor outcomes in CABP have been linked to receiving inappropriate empiric therapy or delayed treatment (tx). LEF, a novel IV/oral pleuromutilin, demonstrated efficacy/safety in noninferiority studies (LEAP 1/2) vs. MOX in adults with CABP. We report efficacy/safety of LEF in patients with LP based on a pooled analyses of LEAP 1/2 data.MethodsIn LEAP 1, PORT III–V patients received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF for 5 days or oral MOX for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 hours after first dose in the intent-to-treat (ITT; all randomized patients) population and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (received ≥1 dose) and clinically evaluable (met predefined evaluability criteria) populations. LP was identified from baseline (BL) samples by culture, serology (IgG, Zeus L. pneumophila group 1–6 indirect fluorescent antibody assay), urine antigen testing (BinaxNOW), and real-time PCR (positive for ssrA). Efficacy analyses herein were done in the microbiological ITT (microITT, treated patients with BL CABP-causing pathogen), microITT-2 (no PCR), and microbiologically evaluable populations; safety analyses included all randomized/treated patients.ResultsOf 65 pooled microITT patients, median age was 60 y, 66% were male, 51% had a normal renal function, and 54%/25% were PORT III/IV. LP was identified in 9.3% (34/364) of LEF patients (7 [20.6%]/19 [55.9%]/8 [23.5%] PORT II/III/IV) and in 9.0% (31/345) of MOX patients (7 [22.6%]/16 [51.6%]/8 [25.8%] PORT II/III/IV), primarily by urine antigen or serology (table). Patients with LP in both tx groups achieved high and similar responses across all endpoints (Figures 1 and 2). In both tx groups, TEAE rates were low and comparable (~32%) and most were mild to moderate; 5 patients (3 LEF; 2 MOX) had treatment-emergent SAEs, all unrelated to tx. No patients died due to TEAEs; no LEF patients and 2 MOX patients discontinued tx due to TEAEs.ConclusionLEF appears to be as safe and effective as MOX in treating patients with LP, including when given as short-course (5 days) oral therapy. Disclosures All authors: No reported disclosures.