Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Jun:29:434-443.
doi: 10.1016/j.jgar.2021.10.021. Epub 2021 Nov 14.

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

Susanne Paukner  1 , Lisa Goldberg  2 , Elizabeth Alexander  2 , Anita F Das  3 , Stefanie Heinrich  4 , Pritty Patel  5 , Gregory J Moran  6 , Christian Sandrock  7 , Thomas M File Jr  8 , Jorge E Vidal  9 , Ken B Waites  10 , Steven P Gelone  2 , Jennifer Schranz  2
Affiliations
Free article
Clinical Trial

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

Susanne Paukner et al. J Glob Antimicrob Resist. 2022 Jun.
Free article

Abstract

Objectives: 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.

Methods: 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).

Results: 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.

Conclusion: Lefamulin is a valuable IV and oral monotherapy option for empirical and directed CABP treatment in adults.

Keywords: CABP; Community-acquired bacterial pneumonia; Efficacy; Lefamulin; Microbiology; Moxifloxacin.

PubMed Disclaimer

Conflict of interest statement

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.

Comment in

Publication types