Treatment of Community-Acquired Pneumonia: A Focus on Lefamulin.

Lefamulin is the first pleuromutilin antibiotic approved for the treatment of bacterial infections in humans. Pleuromutilin antibiotics exert their unique mechanism of action which makes them less susceptible to the development of bacterial resistance and low probability of cross-resistance to the other antimicrobial classes.The authors present a critical review of the pharmacology, pharmacokinetics (PK), pharmacodynamics (PD), and data from two pivotal clinical trials of lefamulin in patients with community-acquired bacterial pneumonia (CABP).Lefamulin exhibits both bactericidal and bacteriostatic activity against gram-positive, fastidious gram-negatives, atypical pathogens, and some gram-negative anaerobes. It has shown activity against organisms known to cause sexually transmitted infections, including Mycoplasma genitalium and drug-resistant Neisseria gonorrhoeae. Lefamulin demonstrated no activity against Enterobacteriaceae or Pseudomonas aeruginosa.Pharmacokinetic studies involving lefamulin in acutely ill patients at least 18 years of age with three or more CABP symptoms failed to reveal any clinically significant differences in the PK parameters on the basis of age, sex, race, weight, or renal impairment. Lefamulin 600 mg tablets had a mean oral bioavailability of 25%. Consumption of high-fat meals may slightly reduce the blood level of the drug.In two phase 3 clinical trials, The Lefamulin Evaluation Against Pneumonia 1 and 2 (LEAP 1 and 2) compared the efficacy and safety of lemafulin with moxifloxacin in patients diagnosed with CABP. Lemafulin administered 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.