, Volume 79, Issue 17, pp 1867–1876 | Cite as

Leave it to Lefamulin: A Pleuromutilin Treatment Option in Community-Acquired Bacterial Pneumonia

  • Young Ran LeeEmail author
  • Katy Louise Jacobs
Review Article


Lefamulin (BC-3781) is the first systemic pleuromutilin antibiotic found to be safe and effective in the treatment of community-acquired bacterial pneumonia (CABP) in humans. This novel antibiotic was developed to combat the increasing incidence of bacterial resistance to current therapies. As the first semisynthetic pleuromutilin for systemic use in humans, lefamulin has demonstrated efficacy against the most common bacteria responsible for CABP, including strains exhibiting resistance to macrolides, fluoroquinolones, tetracyclines, vancomycin, and beta-lactams. In vitro studies have demonstrated efficacy against Staphylococcus aureus, beta-hemolytic and viridans group streptococci, coagulase-negative staphylococci, Enterococcus faecium, Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophilia, and Moraxella catarrhalis at MIC values lower than those of currently available therapies. Two phase III trials (LEAP-1 and LEAP-2) have demonstrated similar findings, meeting non-inferiority criteria for CABP with a minimal side-effect profile. Pharmacokinetic and pharmacodynamic evaluations have shown sufficient drug levels in plasma, subcutaneous adipose tissue, skeletal muscle, and epithelial lining fluid, warranting further investigation for other clinical uses. Lefamulin was approved by the United States Food and Drug Administration (FDA) on 19 August 2019 for the treatment of CABP.


Compliance with Ethical Standards


No funding was received for the preparation of this article.

Conflict of Interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Global Health Estimates 2016: deaths by cause, age, sex, by country and by region, 2000–2016. Geneva, World Health Organization. 2018. Accessed 12 Sep 2019.Google Scholar
  2. 2.
    Rui P, Kang K, Ashman JJ. National hospital ambulatory medical care survey: 2016 emergency department summary tables. 2016.
  3. 3.
    Center for disease control and prevention: national vital statistics reports, Vol. 67, No. 5, July 26, 2018. Table I–12.
  4. 4.
    Cilloniz C, Martin I, Garcia C, San Jose A, Torres A. Microbial etiology of pneumonia: epidemiology, diagnosis, and resistance patterns. Int J Mol Sci. 2016; 17(12): 2120. (Published online 2016 Dec 16).
  5. 5.
    ​Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. Pharm Ther. 2015;40(4):277–83.Google Scholar
  6. 6.
    American Thoracic Society: Top 20 Pneumonia Facts 2018. Accessed 6 Jun 2019.
  7. 7.
    National Center for Biotechnology Information. PubChem Database. Tiamulin, CID=443604, Accessed 8 Jun 2019.
  8. 8.
    Parish L, Parish J. Retapamulin: a new topical antibiotic for the treatment of uncomplicated skin infections. Drugs Today (Barc). 2008;44(2):91–102. Scholar
  9. 9.
    Sader H, Paukner S, Ivezic-Schoenfeld Z, Biedenbach D, Schmitz F, Jones R. Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms responsible for community acquired respiratory tract infections (CARTIs). J Antimicrob Chemother. 2012;67(5):1170–5. 2012 Jan 27).CrossRefPubMedGoogle Scholar
  10. 10.
    Eyal Z, Matzov D, Krupkin M, et al. A novel pleuromutilin antibacterial compound, its binding mode and selectivity mechanism. Sci Rep. 2016;6:39004. (Published 2016 Dec 13).
  11. 11.
    Rodvold KA. Introduction: lefamulin and pharmacokinetic/pharmacodynamic rationale to support the dose selection of lefamulin. J Antimicrob Chemother. 2019;74(Supplement_3):iii2–iii4.
  12. 12.
    Paukner S, Sader H, Ivezic-Schoenfeld Z, Biedenbach D, Jones R. Antimicrobial activity of the pleuromutilin antibiotic BC-3781 against bacterial pathogens isolated in the SENTRY antimicrobial surveillance program in 2010. Antimicrob Agents Chemother. 2013;57(9):4489–95. 2013 Jul 8).CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Mendes R, Paukner S, Doyle T, et al. Low prevalence of gram-positive isolates showing elevated MIC results during the SENTRY surveillance program for 2015-2016 and characterization of resistance mechanisms. Antimicrob Agens Chemother. 2019;63(4):e02158-18. 2019 Jan 22).CrossRefGoogle Scholar
  14. 14.
    Rubino C, Xue B, Bhavnani S, et al. Population pharmacokinetic analysis for BC-3781 using phase 2 data from patients with acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2015;59(1):282–8. 2014 Oct 27).CrossRefPubMedGoogle Scholar
  15. 15.
    Zeitlinger M, Schwameis 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 Chemother. 2016;71:1022–6. Scholar
  16. 16.
    Bhavnani S, Zhang L, Hammel J, et al. Pharmacokinetic/pharmacodynamics target attainment analysis to support intravenous and oral lefamulin dose selection for the treatment of patients with community acquired bacterial pneumonia. J Antimicrob Chemother. 2019;74(Supplement_3):iii35–iii41.
  17. 17.
    Xenleta (lefamulin) [prescribing information]. King of Prussia, PA: Nabriva Therapeutics US, Inc. 2019.Google Scholar
  18. 18.
    Mendes R, Farrell D, Flamm R, et al. In vitro activity of lefamulin tested against Streptococcus pneumoniae with defined serotypes, including multidrug-resistant isolates causing lower respiratory tract infections in the United States. Antimicrob Agents Chemother. 2016;60(7):4407–4411. (Published 2016 Jun 20).
  19. 19.
    ​Wicha W, Craig W, Andes D. In vivo pharmacodynamics of lefamulin, the first systemic pleuromutilin for human use, in a neutropenic murine thigh infection model. J Antimicrob Chemother. 2019;74(Supplement_3):iii5–iii10.
  20. 20.
    ​Wicha W, Strickmann D, Paukner S. Pharmacokinetics/pharmacodynamics of lefamulin in a neutropenic murine pneumonia model with Staphylococcus aureus and Streptococcus pneumoniae. J Antimicrob Chemother. 2019;74(Supplement_3):iii11–iii18.
  21. 21.
    ​File T, Goldberg L, Das A, et al. Efficacy and safety of IV-to-oral lefamulin, a pleuromutilin antibiotic, for treatment of community-acquired bacterial pneumonia: the phase 3 LEAP 1 trial. Clin Infect Dis. 2019. [Epub ahead of print].
  22. 22.
    ​Alexander E, et al. Abstract LB6. Presented at: IDWeek. 2018. San Francisco.Google Scholar
  23. 23.
    ​Prince W, Ivezic-Schoenfeld Z, Lell C, et al. 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(5):2087–94. 2013 Feb 19).CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Moxifloxacin. In: Lexi-Drugs [database online]. Hudson, Ohio: Wolters-Kluwer Health.2019. Accessed 15 Sep 2019.Google Scholar
  25. 25.
    Linezolid. In: Lexi-Drugs [database online]. Hudson, Ohio: Wolters-Kluwer Health. 2019. Accessed 15 Sep 2019.Google Scholar
  26. 26.
    Metlay J, Waterer G, Long A, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45–e67.
  27. 27.
    Metersky ML, Ma A, Houck PM, Bratzler DW. Antibiotics for bacteremic pneumonia: Improved outcomes with macrolides but not fluoroquinolones. Chest. 2007;131:466.CrossRefGoogle Scholar
  28. 28.
    Paukner S, Gruss A, Jensen J. In vitro activity of lefamulin against sexually transmitted bacterial pathogens. Antimicrob Agents Chemother. 2018;6:25. (Print 2018 May).
  29. 29.
    Jacobsson S, Paukner S, Golparian D, Jensen JS, Unemo M. 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(11):e01497-17. (Published 2017 Oct 24).

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmacy Practice, Jerry H. Hodge School of PharmacyTexas Tech University Health Sciences CenterAbileneUSA

Personalised recommendations