Treatment of Community-Acquired Pneumonia: A Focus on Lefamulin

OBJECTIVE: The goal of this article is to review the clinical pharmacology, pharmacokinetics, efficacy, and safety of lemafulin. DATA SOURCES: We performed a systematic literature review using the search terms of lefamulin and BC-3781 in the PubMed and EMBASE databases. We also cross-referenced the pertinent articles and searched ClinicalTrials.gov to identify ongoing and nonpublished studies. STUDY SELECTION AND DATA EXTRACTION: Published data from 2005 to 2019 evaluating the clinical pharmacology, efficacy, and safety studies of lefamulin were analyzed. DATA SYNTHESIS: In phase 3 clinical trials, two multicenter, randomized double-blinded studies—Lefamulin Evaluation Against Pneumonia 1 and 2 (LEAP 1 and 2)—compared the efficacy and safety of lemafulin with moxifloxacin in patients diagnosed with community-acquired bacterial pneumonia (CABP). Lemafulin given in doses of 600 mg orally or 150 mg intravenously were reported to have comparable efficacy to those of moxifloxacin with or without linezolid in patients with CABP. After the trial, the lefamulin group had an early clinical response (ECR) of 87.3% and the moxifloxacin group had an ECR of 90.2%. The difference of − 2.9% in the ECR was non-significant (CI − 8.5, 2.8). RELEVANCE TO PATIENTS AND CLINICAL PRACTICE: Lemafulin exhibits a unique binding property; therefore, it possess a potentially lower predisposition for the development of bacterial resistance and cross-resistance to other antimicrobial classes. Lefamulin is active against gram-positive including methicillin-resistant strains and atypical organisms which are often implicated in CABP. Lefamulin may be a safe alternative for adult patients with CABP who may not be candidates for respiratory fluoroquinolones. Lefamulin demonstrates both bactericidal and bacteriostatic activity against gram-positive, fastidious gram-negatives, atypical pathogens, and some gram-negative anaerobes. It is bactericidal in vitro against Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae (including macrolide-resistant strains) at concentrations of 0.06, 0.5, and 0.008 µg/ml respectively, and bacteriostatic against Staphylococcus aureus and Streptococcus pyogenes. The agent also demonstrates both time- and concentration-dependent killing against the pathogens S. pneumoniae and S. aureus. In vitro susceptibility testing demonstrated an MIC(50/90) of 0.06/0.12 µg/ml against S. pneumoniae and S. aureus. The SENTRY Antimicrobial Surveillance Program found that at a concentration ≤ 1 µg/ml, lefamulin inhibited 100% S. pneumoniae isolates, 99.8% of S. aureus isolates, and 99.6% of methicillin-resistant S. aureus isolates. It was not affected by resistance to various antibiotic classes such as beta-lactams, fluoroquinolones, or macrolides.