lefamulin
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Neumonía bacteriana adquirida en la comunidad en adultos por microorganismos sensibles.
Contraindicaciones
Absolutas
- Hipersensibilidad a lefamulina. Para la vía oral, uso concomitante de sustratos sensibles de CYP3A4 que prolongan QT.
Advertencias clínicas
- Puede prolongar QT; evita con QT prolongado, arritmia ventricular, hipopotasemia o con otros fármacos que prolongan QT. — DailyMed, set_id eb972ea8-7502-422e-84bb-66cb8e93ca06
Interacciones medicamentosas
- SeveraInhibidores o inductores de CYP3A/P-gp
Mecanismo: Los inhibidores pueden aumentar la exposición de forma dependiente de la vía; los inductores fuertes o moderados de CYP3A4/P-gp pueden reducirla.
Recomendación: Evita inhibidores fuertes con la vía oral y sigue las recomendaciones específicas para la vía IV. Evita inductores fuertes o moderados salvo que el beneficio supere el riesgo.
DailyMed, set_id eb972ea8-7502-422e-84bb-66cb8e93ca06
- SeveraFármacos que prolongan QT
Mecanismo: La prolongación de repolarización puede ser aditiva.
Recomendación: Evita la combinación o controla ECG y electrolitos.
DailyMed, set_id eb972ea8-7502-422e-84bb-66cb8e93ca06
Eventos adversos
Comunes (≥1%)
Diarrea, náuseas, vómitos, reacción de perfusión y elevación de enzimas hepáticas
Raros pero graves
Torsades de pointes y colitis por C. difficile
Embarazo y lactancia
Puede causar daño fetal. Usa anticoncepción eficaz durante el tratamiento y durante 2 días después. Extrae y desecha la leche durante el tratamiento y durante 2 días después.
Bibliografía reciente (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.