Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic

  title={Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic},
  author={Michael P. Veve and Jamie L. Wagner},
  journal={Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy},
  • M. VeveJamie L. Wagner
  • Published 20 August 2018
  • Biology, Medicine
  • Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
The emergence and spread of antimicrobial resistance have led to a global public health emergency requiring development of new antimicrobial classes. Lefamulin (formally BC‐3781) is a novel pleuromutilin antibiotic currently undergoing Food and Drug Administration review for community‐acquired bacterial pneumonia (CABP) as intravenous (IV) and oral (PO) formulations. Although pleuromutilin antibiotics were first developed in the 1950s, lefamulin is the first to be used for systemic treatment of… 

Lefamulin: A Novel Semisynthetic Pleuromutilin Antibiotic for Community-Acquired Bacterial Pneumonia.

  • R. WatkinsT. File
  • Biology, Medicine
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2020
This review summarizes the available data about lefamulin, including recent evidence from two phase III clinical trials (LEAP 1 and LEAP 2), and discusses its potential role in the treatment of CABP.

Clinical Utility of Lefamulin: If Not Now, When?

Lefamulin is a well-tolerated agent with a unique mechanism, availability in both IV and PO formulations, and it has been rigorously studied for safety and efficacy for CABP.

Lefamulin: a promising new pleuromutilin antibiotic in the pipeline

The drug displays potent activity against several pathogens common in both acute bacterial skin and skin structure infections and CABP, and a lack of cross-resistance with other antibiotic classes for S. pneumoniae and Staphylococcus aureus.

Lefamulin: a New Hope in the Field of Community-Acquired Bacterial Pneumonia

This review aims to highlight the pre-existing treatment options and specific purposes to shed some light upon the development of a new drug lefamulin and its specifications and explore this novel drug’s superior efficacy to already existing treatment strategies.

Lefamulin: A Novel Oral and Intravenous Pleuromutilin for the Treatment of Community-Acquired Bacterial Pneumonia

Lefamulin represents a safe and effective option for treating CABP in cases of antimicrobial resistance to first-line therapies, clinical failure, or intolerance/adverse effects to currently used agents.

An overview of lefamulin for the treatment of community acquired bacterial pneumonia

Its particular mechanism of action, affecting ribosomal protein synthesis, provides a low probability of cross-resistance to other commonly used antibiotics in CAP, which makes it a good alternative for outpatient treatment of CAP.

Lefamulin vs moxifloxacin for community-acquired bacterial pneumonia

Clinical efficacy and tolerability for lefamulin in the treatment of CABP were similar to those for moxifloxacin and lefamulin was associated with a similar risk of adverse events as moxIFlOxacin.

Spotlight on New Antibiotics for the Treatment of Pneumonia

  • A. Russo
  • Medicine, Biology
    Clinical medicine insights. Circulatory, respiratory and pulmonary medicine
  • 2020
There are reported characteristics of newly approved antibiotics that represent potential future options for the treatment of respiratory tract infections, including those caused by multidrug-resistant bacteria.

In vitro Activity of Lefamulin Against the Common Respiratory Pathogens Isolated From Mainland China During 2017–2019

In vitro activity supports the use of lefamulin in the treatment of CABP in China and has good and broad-spectrum coverage of respiratory pathogens.

The clinical efficacy of lefamulin in the treatment of elderly patients with community-acquired bacterial pneumonia

A metaanalysis was done to investigate the clinical efficacy of lefamulin in the treatment of elderly patients with CABP and found no significant differences in terms of early clinical response rate or investigator assessment of clinical response at test of cure (TOC).



Efficacy of Lefamulin Against Staphylococcus aureus-Induced Bacteremia in a Neutropenic and Immunocompetent Murine Model

This study investigated the efficacy of LEF and comparators against SA in a neutropenic and immunocompetent murine bacteremia model and showed comparable therapeutic outcome to DAP or VAN in this acute experimental infection model, while showing superior killing as compared with LZD or TGC.

The pleuromutilin antibiotics: a new class for human use.

The key properties of pleuromutilin derivatives, designed primarily through modifications at the C(14) side chain, are presented, and the potential of these compounds in systemic therapy in humans is discussed.

Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs).

BC-3781 was very active against organisms commonly associated with CARTIs and its activity was not negatively influenced by resistance to other antimicrobials.

Pleuromutilins: Potent Drugs for Resistant Bugs-Mode of Action and Resistance.

Overall, pleuromutilins and, in particular, lefamulin are characterized by potent activity against Gram-positive and fastidious Gram-negative pathogens as well as against mycoplasmas and intracellular organisms, such as Chlamydia spp.

Antimicrobial Activity of the Investigational Pleuromutilin Compound BC-3781 Tested against Gram-Positive Organisms Commonly Associated with Acute Bacterial Skin and Skin Structure Infections

Compared with other antibiotics in use for the treatment of ABSSSI, BC-3781 displayed the lowest MICs and only a minimal potential for cross-resistance with other antimicrobial classes.

Antimicrobial Activity of the Pleuromutilin Antibiotic BC-3781 against Bacterial Pathogens Isolated in the SENTRY Antimicrobial Surveillance Program in 2010

In all, BC-3781 displayed a very potent antibacterial profile including the most prevalent bacterial pathogens causing ABSSSI and CABP, thus warranting further clinical development of this antibiotic in these and possibly other indications.

Are pleuromutilin antibiotics finally fit for human use?

  • R. Novak
  • Medicine
    Annals of the New York Academy of Sciences
  • 2011
Key aspects of this antibacterial class are discussed and some insight is provided into the question of why it took half a century to develop a systemic pleuromutilin for human use is provided.

Phase II Clinical Study of BC-3781, a Pleuromutilin Antibiotic, in Treatment of Patients with Acute Bacterial Skin and Skin Structure Infections

Results provide the first proof of concept for the systemic use of a pleuromutilin antibiotic for the treatment of ABSSSIs and when BC-3781 was used to treat ABSSSI caused by a Gram-positive pathogen, including MRSA, clinical success rates were comparable to those of the comparator, vancomycin.

Mycoplasma pneumoniae: Current Knowledge on Macrolide Resistance and Treatment

Macrolides and related antibiotics are the first-line treatment of M. pneumoniae respiratory tract infections mainly because of their low MIC against the bacteria, their low toxicity and the absence of contraindication in young children, but macrolide resistance has been spreading for 15 years worldwide.

New Horizons in Mycoplasma genitalium Treatment

Data for new investigational antimicrobials such as the ketolide solithromycin suggest that this drug may eventually prove useful in management of some resistant M. genitalium infections, although it is not likely to achieve cure rates >80% in macrolide-resistant strains, in a similar range as recently reported for pristinamycin.