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

Zhanel, George G.; C, Deng; Zelenitsky, Sheryl; Lawrence, Courtney K.; Adam, Heather J.; Golden, Alyssa; Berry, Liam; Schweizer, Frank; Zhanel, Michael A.; Irfan, Neal; Bay, Denice C.; Lagacé-Wiens, Philippe; Walkty, Andrew; Mandell, Lionel A.; Lynch, Joseph P.; Karlowsky, James A.

doi:10.1007/s40265-020-01443-4

Cited by 30 publications

(21 citation statements)

References 43 publications

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“…Lefamulin also exerts activity against S. aureus, MRSA, and vancomycin-resistant E. faecium. 88 The adverse effects of lefamulin include prolonged QT interval (increases the risk of kidney failure or liver dysfunction in patients), infusion reactions, diarrhea, nausea, hypokalemia, insomnia, and headaches. 89 Ceftolozane/tazobactam is a combination of ceftolozane, a novel cephalosporin antibiotic, and tazobactam, a betalactamase inhibitor.…”

Section: Dovepressmentioning

confidence: 99%

Development and Research Progress of Anti-Drug Resistant Bacteria Drugs

Cui¹,

Lü²,

Yue³

2021

IDR

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Bacterial resistance has become increasingly serious because of the widespread use and abuse of antibiotics. In particular, the emergence of multidrug-resistant bacteria has posed a serious threat to human public health and attracted the attention of the World Health Organization (WHO) and the governments of various countries. Therefore, the establishment of measures against bacterial resistance and the discovery of new antibacterial drugs are increasingly urgent to better contain the emergence of bacterial resistance and provide a reference for the development of new antibacterial drugs. In this review, we discuss some antibiotic drugs that have been approved for clinical use and a partial summary of the meaningful research results of anti-drug resistant bacterial drugs in different fields, including the antibiotic drugs approved by the FDA from 2015 to 2020, the potential drugs against drug-resistant bacteria, the new molecules synthesized by chemical modification, combination therapy, drug repurposing, immunotherapy and other therapies.

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Section: Dovepressmentioning

confidence: 99%

Development and Research Progress of Anti-Drug Resistant Bacteria Drugs

Cui¹,

Lü²,

Yue³

2021

IDR

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“…Lefamulin (formerly BC‐3781) is a semi‐synthetic agent within the pleuromutilin derivative class of antibiotics [11], discovered in 2006 [12]. With the first (and namesake) agent in the class discovered in the 1950s [13], pleuromutilin derivatives were employed only for veterinary use until the approval of retapamulin (Altabax) in 2007, a topical agent for the treatment of impetigo due to methicillin‐susceptible S. aureus or Streptococcus pyogenes [14,15].…”

Section: Mechanism Of Action and Spectrum Of Activitymentioning

confidence: 99%

“…Pleuromutilin and derivatives consist of a tricyclic core, a ketone group and different C14 side chains. The class inhibits bacterial protein synthesis through binding to the peptidyl transferase centre on the 50S ribosomal subunit [16], with the tricyclic core and C14 side chains interacting at the A (aminoacyl) and P (peptidyl) sites [12], respectively, through hydrophobic and hydrogen bond interactions (Fig. 1).…”

Section: Mechanism Of Action and Spectrum Of Activitymentioning

confidence: 99%

“…These breakpoints correspond with those reported by the Clinical Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing, with the exception that European Committee on Antimicrobial Susceptibility Testing suggests that insufficient evidence is available to establish an H. influenzae breakpoint. Thorough and more in‐depth summaries of in vitro activity of lefamulin and relevant comparators has been previously published [12,13], as well as updated SENTRY data from 2017 for relevant ABSSSIs [25] and CABP [26] organisms.…”

Section: Mechanism Of Action and Spectrum Of Activitymentioning

confidence: 99%

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Clinical use of lefamulin: A first‐in‐class semisynthetic pleuromutilin antibiotic

Covvey

Guarascio

2021

J Intern Med

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Lefamulin is a novel antibiotic agent within the pleuromutilin derivative class approved for the treatment of community‐acquired bacterial pneumonia (CABP) by the United States Food and Drug Administration and the European Commission in 2019 and 2020, respectively. The objective of this article is to provide a summary of clinically relevant data underlying lefamulin and to provide recommendations for its place in therapy. In vitro data establish lefamulin's activity against a number of Gram‐positive, Gram‐negative and atypical organisms relevant in the treatment of CABP, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Mycoplasma pneumoniae and Chlamydophila pneumoniae. Two phase‐3 studies, the Lefamulin Evaluation Against Pneumonia trials, established non‐inferiority of lefamulin against moxifloxacin in the treatment of CABP, including the sequential transition from intravenous to oral therapy and across a broad set of patient demographics and severities. Pooled and post hoc analyses have confirmed these effects for a variety of subgroups and secondary endpoints. Real‐world study data post‐approval have largely not yet emerged for lefamulin, and there is a need for further investigation into safety/efficacy for off‐label indications such as acute bacterial skin and skin structure infections and sexually transmitted infections. Further data regarding tolerability, particularly with long‐term use, as well as the emergence of resistance over time, are still undefined.

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“…Retapamulin was the only pleuromutilin approved for topical use for humans since 2007 (Novak, 2011 ). However, in 2019, the U.S. Food and Drug Administration approved lefamulin, a newly developed pleuromutilin, to treat adults with community‐acquired bacterial pneumonia due to its activity against Staphylococcus aureus , Streptococcus pneumoniae and atypical bacteria (Andrei et al., 2019 ; WHO, 2021 ; Zhanel et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 8: Pleuromutilins: tiamulin and valnemulin

Koutsoumanis¹,

Allende²,

Álvarez‐Ordóñez³

et al. 2021

EFS2

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The specific concentrations of tiamulin and valnemulin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/ increased yield were reported for tiamulin, while for valnemulin no suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these two antimicrobials.

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

Cited by 30 publications

References 43 publications

Development and Research Progress of Anti-Drug Resistant Bacteria Drugs

Development and Research Progress of Anti-Drug Resistant Bacteria Drugs

Clinical use of lefamulin: A first‐in‐class semisynthetic pleuromutilin antibiotic

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 8: Pleuromutilins: tiamulin and valnemulin

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