Pooled microbiological findings and efficacy outcomes by pathogen in adults with community-acquired bacterial pneumonia from the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 phase 3 trials of lefamulin versus moxifloxacin.

Lefamulin, a pleuromutilin antibiotic approved for community-acquired bacterial pneumonia (CABP), was evaluated for microbiological efficacy in a prespecified pooled analysis of LEAP 1 and 2 phase 3 clinical trial data in patients with CABP. In LEAP 1, adults (PORT risk class III‒V) received intravenous (IV) lefamulin 150 mg every 12 h (q12h) for 5‒7 days or moxifloxacin 400 mg every 24 h (q24h) for 7 days, with optional IV-to-oral switch. In LEAP 2, adults (PORT II‒IV) received oral lefamulin 600 mg q12h for 5 days or moxifloxacin 400 mg q24h for 7 days. Primary outcomes were early clinical response (ECR) at 96 ± 24 h after treatment start and investigator assessment of clinical response (IACR) 5‒10 days after the last dose. Secondary outcomes included ECR and IACR in patients with a baseline CABP pathogen (detected via culture, urinary antigen testing, serology and/or real-time PCR). Baseline CABP pathogens were detected in 709/1289 patients (55.0%; microbiological intention-to-treat population). The most frequently identified pathogens were Streptococcus pneumoniae (61.9% of patients) and Haemophilus influenzae (29.9%); 25.1% had atypical pathogens and 33.1% had polymicrobial infections. Pathogens were identified most frequently by PCR from sputum, followed by culture from respiratory specimens. In patients with baseline CABP pathogens, ECR rates were 89.3% (lefamulin) and 93.0% (moxifloxacin); IACR success rates were 83.2% and 86.7%, respectively. Results were consistent across CABP pathogens, including drug-resistant isolates and polymicrobial infections. Lefamulin is a valuable IV and oral monotherapy option for empirical and directed CABP treatment in adults.

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Déclaration de conflit d'intérêts

Declaration of Competing Interests SP and SPG are employees of/stockholders in Nabriva Therapeutics plc; LG, EA and JS were employees of/stockholders in Nabriva Therapeutics plc at the time of the analysis; AFD has served as a consultant for ContraFect, IterumTx, MicuRx, Nabriva Therapeutics, Paratek, Shionogi, Tetraphase, Union Therapeutics and UTILITY; SH and PP are employees of Accelerō® Bioanalytics GmbH and Covance Central Laboratory Services, respectively, which were contracted by Nabriva Therapeutics to assist in the performance of confirmatory and specialised testing for the LEAP 1 and LEAP 2 trials; GJM has received grants from ContraFect and Nabriva Therapeutics; CS has served as a consultant for Allergan and Nabriva Therapeutics, has received grants from the National Institutes of Health and the Health Resources & Services Administration, and has received non-financial support from the State of California; TMF has served as a consultant for bioMérieux, Curetis, Melinta, Merck, Motif BioSciences, Nabriva Therapeutics, Paratek, Pfizer and Shionogi Inc. and has received grants from Nabriva Therapeutics; JEV has received grants or research contracts from the Bill and Melinda Gates Foundation, Melinta Therapeutics, Nabriva Therapeutics, the National Institutes of Health and Pfizer; KBW has received research grants and/or contracts from Akonni Biosystems, Covance, Inc., Everest Pharmaceuticals, mFluiDx, Roche Molecular Systems, SpeeDx, Ltd., US Centers for Disease Control and Prevention (CDC), National Institutes of Health and Wockhardt Ltd.