lefamulin
Sources réglementaires consultées
Indications approuvées
- Pneumonie bactérienne communautaire chez l’adulte due à des germes sensibles.
Contre-indications
Absolues
- Hypersensibilité à la léfamuline. Pour la voie orale, utilisation concomitante de substrats sensibles du CYP3A4 qui allongent le QT.
Mises en garde cliniques
- Il peut prolonger le QT ; éviter en cas de QT long, d’arythmie ventriculaire, d’hypokaliémie ou avec d’autres médicaments allongeant le QT. — DailyMed, set_id eb972ea8-7502-422e-84bb-66cb8e93ca06
Interactions médicamenteuses
- SévèreInhibiteurs ou inducteurs du CYP3A/P-gp
Mécanisme: Les inhibiteurs peuvent augmenter l’exposition selon la voie ; les inducteurs puissants ou modérés du CYP3A4/P-gp peuvent la réduire.
Recommandation: Éviter les inhibiteurs puissants par voie orale et suivre les recommandations propres à la voie IV. Éviter les inducteurs puissants ou modérés sauf si le bénéfice l’emporte sur le risque.
DailyMed, set_id eb972ea8-7502-422e-84bb-66cb8e93ca06
- SévèreMédicaments allongeant le QT
Mécanisme: L’allongement de la repolarisation peut être additif.
Recommandation: Éviter l’association ou surveiller l’ECG et les électrolytes.
DailyMed, set_id eb972ea8-7502-422e-84bb-66cb8e93ca06
Effets indésirables
Communs (≥1%)
Diarrhée, nausées, vomissements, réaction de perfusion et élévation des enzymes hépatiques
Rares mais graves
Torsades de pointes et colite à C. difficile
Grossesse et allaitement
Il peut provoquer une atteinte fœtale. Utiliser une contraception efficace pendant le traitement et pendant 2 jours après. Tirer et jeter le lait pendant le traitement et pendant 2 jours après.
Bibliographie récente (PubMed)
The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST) develops and publishes standards and guidelines for AST methods and results interpretation in an annual update to the Performance Standards for Antimicrobial Susceptibility Testing (M100). This minireview will discuss changes to M100 for the 31st edition, including new and revised breakpoints and testing recommendations. New MIC and disk diffusion breakpoints are described for azithromycin (Shigella spp.), imipenem-relebactam (Enterobacterales, Pseudomonas aeruginosa, and anaerobes), and lefamulin (Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae), and disk breakpoints are described for azithromycin and Neisseria gonorrhoeae. The rationale behind revised oxacillin MIC breakpoints for select staphylococci is discussed. Updates to test methods include a method for disk diffusion using positive blood culture broth and use of linezolid to predict tedizolid susceptibility. There is clarification on which drugs to suppress on bacteria isolated from the cerebrospinal fluid and clarification on the use of a caret symbol attached to the intermediate category ("I^") to indicate those antimicrobials that concentrate in the urine.
Lefamulin (Xenleta) has been approved by the US FDA for the treatment of community-acquired bacterial pneumonia (CABP). It may be taken intravenously or orally and has activity against a broad range of pulmonary pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumonia, as well as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Lefamulin has an adverse effect profile that is similar to other antimicrobial agents commonly used to treat CABP. Despite these promising features, the use of lefamulin remains limited in clinical practice. However, given the rise of antibiotic-resistant organisms, this may soon change. This review examines what is known about the pharmacokinetics and pharmacodynamics of lefamulin and looks ahead to its potential applications in clinical practice, including the treatment of sexually transmitted infections such as multidrug-resistant Mycoplasma genitalium, as well as its role as a synergistic agent used in combination with other antimicrobials in the treatment of drug-resistant organisms.
This review discusses small molecule antibiotics approved for clinical use in the time frame 2010-2022. This time span saw the approval of four synthetic antibiotics (bedaquiline, pretomanid, delafloxacin, tedizolid), nine natural product derivatives (ceftaroline fosamil, cefiderocol, plazomicin, omadacycline, eravacycline, sarecycline, lefamulin, dalbavancin, oritavancin), and one natural product (fidaxomicin).
Methicillin-resistant Staphylococcus aureus infections are increasing in prevalence in patients with cystic fibrosis (CF) and are associated with worsening lung function and increased mortality. Lefamulin is a pleuromutilin antimicrobial approved to treat community-acquired bacterial pneumonia based on potent in vitro activity and clinical efficacy. This Phase I, open-label, randomized crossover study assessed the safety and pharmacokinetic profile of oral and intravenous (IV) lefamulin in adults with CF. The study comprised 2 dosing periods in which adults with CF (N = 13) received a single dose of lefamulin via a 150-mg IV infusion or 600-mg immediate-release orally administered tablet, separated by a 4- to 7-day washout period. Pharmacokinetic and safety parameters were assessed after lefamulin treatment. Single doses of lefamulin administered via oral tablet or IV infusion resulted in comparable drug exposure, and sputum analysis suggested rapid penetration of lefamulin into the lung. Comparison of the present results with those obtained from prior single-dose studies of healthy volunteers indicate no meaningful difference in the pharmacokinetic properties of lefamulin in patients with CF. Treatment-emergent adverse events were consistent with previous reports, and the majority were mild in severity. These results show similar lefamulin pharmacokinetic and safety profiles between patients with CF and healthy volunteers receiving the same oral and IV doses, suggesting no need for lefamulin dose adjustment in patients with CF and indicating the potential of lefamulin as therapy for lung infections in patients with CF. gov identifier: NCT05225805.