New antibiotics are a rarity these days, let alone new antibiotic classes. But in August 2019, the United States Food and Drug Administration (FDA) approved lefamulin (Xenleta), the first of the broad-spectrum pleuromutilins, for treating patients with bacterial pneumonia.
The investigators randomised 738 ambulatory patients (mean age, 57) with community-acquired pneumonia (CAP) to either oral lefamulin (twice daily for 5 days) or oral moxifloxacin (daily for 7 days). Patients were recruited from 19 countries, primarily in Eastern Europe; 40% were smokers; and most had comorbidities.
Overall, the drugs performed equally well, with about 90% of each group being clinically improved after 4 days and also after treatment cessation. Responses also were equally good for the subgroup in whom a bacterial pathogen was identified, including the very few patients with drug-resistant pneumococcus or methicillin-resistant Staphylococcus aureus.
Lefamulin recipients were significantly more likely than moxifloxacin recipients to report gastrointestinal side effects (18% vs. 8%), most often diarrhoea and vomitting. Too few patients were bacteraemic to allow a good assessment of drug response among them.
However, Clinicians emphatically should not waste this one on routine cases of CAP. The manufacturer (Nabriva) suggests that the mechanism of action of the pleuromutilins (i.e., they inhibit bacterial protein synthesis) means they will be relatively slow to induce resistance.
Time will tell, but for now, lefamulin should be reserved for either managing infections that fail to respond to older drugs or treating patients who cannot take older drugs.