Abstract
Lefamulin is the first pleuromutilin to be used systemically in humans and was approved in the United States for treatment of community-acquired bacterial pneumonia in 2019. Pleuromutilin is a natural antibiotic first discovered in the 1950s from an edible mushroom—Pleurotus mutilus. The pleuromutilins are semisynthetic derivatives of the parent compound that have been used in veterinary medicine for over 3 decades with little evidence of resistant development. Lefamulin has a unique mechanism of action that inhibits protein synthesis by preventing the binding of tRNA for peptide transfer. It is active against typical and atypical bacteria that are causes of community-acquired pneumonia and is available in parenteral and oral formulations. The pharmacokinetics, microbial activity, clinical efficacy, and safety profile in phase 3 trials, and place in therapy are reviewed in this chapter.
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References
Paukner S, Riedl R. Pleuromutilins: potent drugs for resistant bugs—mode of action and resistance. Cold Spring Harb Perspect Med. 2017;7:a027110.
Heilmann C, Jensen L, Lundstrom K, Windsor D, Webster. Treatment of resistant mycoplasmas infection in immunocompromised patients with a new pleuromutilin antibiotic. J Infect. 2001;43:234–8.
Veve MP, Wagner JL. Lefamulin: review of a promising novel pleuromutilin antibiotic. Pharmacotherapy. 2018;38:935–46.
Waiters KB, Crabb DM, Duffy LB, et al. In vitro activities of lefamulin and other antimicrobial agents against macrolide-susceptible and macrolide-resistant mycoplasma pneumoniae from the United States, Europe and China. Antimicrob Agents Chemother. 2017;61:e02008–16.
Paukner S, Gruss A, Jensen JS. In vitro activity of lefamulin against sexually transmitted bacterial pathogens. Antimicrob Agents Chemother. 2018;62:e02330–17.
Jacobson S, Paukner S, Golparian, et al. In vitro activity of the novel pleuromutilin lefamulin [BC-3781] and effect of efflux pump inactivation on multidrug-resistant and extensively drug-resistant Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2017;61:e01497–17.
Paukner S, Sader HS, Ivezic-Schoenfeld Z, et al. Antimicrobial activity of the pleuromutilin antibiotic BC-3781 against bacterial pathogens isolated in the SENTRY antimicrobial surveillance program in 20210. Antimicrob Agents Chemother. 2013;57:4489–95.
Wicha WW, Prince WT, Lell C, Heilmayer W, Gelone SP. Pharmacokinetics and tolerability of lefamulin following intravenous and oral dosing. J Antimicrob Chemother. 2019;74(Suppl 3):iii9–26.
Zeitlinger M, Schwarmeis R, Burian A, et al. Simultaneous assessment of the pharmacokinetics of a pleuromutilin, lefamulin, in plasma, soft tissues, and pulmonary epithelial lining fluid. J Antimicrob Agents Chemother. 2016;71:1022–6.
Watkins RR, File TM Jr. Lefamulin: a novel semisynthetic pleuromutilin antibiotic for community-acquired bacterial pneumonia. Clin Infect Dis. 2020;71:2757–62.
File TM, Goldberg L, Das A, et al. Efficacy and safety of intravenous-to-oral lefamulin, a pleuromutilin antibiotic, for the treatment of community-acquired bacterial pneumonia: the phase III Lefamulin evaluation against pneumonia [LEAP I] trial. Clin Infect Dis. 2019;69:1856–67.
Alexander E, Goldberg L, Das AF, et al. Oral lefamulin vs moxifloxacin for early clinical response among adults with community-acquired bacterial pneumonia: the LEAP 2 randomized clinical trial. JAMA. 2019;322:1661–71.
Prince WT, Ivezic-Schoenfeld Z, Lell C, Tack KJ, Novak R, Obermayr F, Talbot GH. Phase II clinical study of BC-3781, a pleuromutilin antibiotic. In treatment of patients with acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2013;57:2087–94.
Jacobsson S, Paukner S, golparian D, et al. In vitro activity of the novel pleuromutilin lefamulin [BC-3781] and efflux pump inactivation on multidrug-resistant and extensively drug-resistant Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2017;61:e01497–17.
Jensen JS, Paulner S. Lefamulin is highly active in vitro against multi-drug resistant Mycoplasma genitalium strains. Poster/abstract. In: 27th European congress of clinical microbiology and infectious diseases, 22–25 April. Vienna; 2017.
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Fong, I.W. (2023). Pleuromutilin: A New Class of Antibiotic: Lefamulin. In: New Antimicrobials: For the Present and the Future. Emerging Infectious Diseases of the 21st Century. Springer, Cham. https://doi.org/10.1007/978-3-031-26078-0_8
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DOI: https://doi.org/10.1007/978-3-031-26078-0_8
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