Lefamulin: A Novel Semisynthetic Pleuromutilin Antibiotic for Community-Acquired Bacterial Pneumonia.
antimicrobial resistance; community-acquired bacterial pneumonia; lefamulin
Community-acquired bacterial pneumonia (CABP) remains a significant cause of morbidity and mortality worldwide. Antimicrobial resistance, including in pathogens that cause CABP, continues to spread at an alarming rate. Because of these factors, the development of new antibiotic classes is urgently needed. Lefamulin, previously known as BC-3781, is a semisynthetic pleuromutilin antibiotic that was approved by the Federal Drug Administration for the treatment of CABP in adults. Available in both oral and intravenous (IV) formulations, lefamulin has potent in vitro activity against both typical and atypical CABP pathogens. The first pleuromutilin to be used systemically in humans, lefamulin has a unique mechanism of action that inhibits protein synthesis by preventing the binding of tRNA for peptide transfer. 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.
Watkins Richard R; File Thomas M
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2020
2020-03-28
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1093/cid/ciaa336" target="_blank" rel="noreferrer noopener">10.1093/cid/ciaa336</a>
An Integrated Safety Summary of Omadacycline, a Novel Aminomethylcycline Antibiotic
COMMUNICABLE diseases; community-acquired bacterial pneumonia; COMMUNITY-acquired pneumonia; DENTAL discoloration; omadacycline; PATIENT safety; safety; skin and skin structure infections; SKIN diseases; TEETH abnormalities; TETRACYCLINE; THERAPEUTIC use
Omadacycline is a semisynthetic tetracycline antibiotic. Phase III clinical trial results have shown that omadacycline has an acceptable safety profile in the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Similar to most tetracyclines, transient nausea and vomiting and low-magnitude increases in liver aminotransferases were the most frequent treatment-emergent adverse events in phase III studies but were not treatment limiting. Package insert warnings and precautions for omadacycline include tooth discoloration; enamel hypoplasia; inhibition of bone growth following use in late pregnancy, infancy, or childhood up to 8 years of age; an imbalance in mortality (2%, compared with 1% in moxifloxacin-treated patients) was observed in the phase III study in patients with community-acquired bacterial pneumonia. Omadacycline has no effect on the QT interval, and its affinity for muscarinic M2 receptors resulted in transient heart rate increases following dosing.
Opal Steven; File Thomas M; van der Poll Tom; Tzanis Evan; Chitra Surya; McGovern Paul C
Clinical Infectious Diseases: An Official Publication Of The Infectious Diseases Society Of America
2019
2019-08
<a href="http://doi.org/10.1093/cid/ciz398" target="_blank" rel="noreferrer noopener">10.1093/cid/ciz398</a>