Lefamulin (Xenleta) for Community-Acquired Bacterial Pneumonia

Abstract

Lefamulin (Xenleta -Nabriva), a semisynthetic pleuromutilin antibiotic, has been approved by the FDA for IV and oral treatment of community-acquired bacterial pneumonia (CABP) in adults. It is the first systemic pleuromutilin antibiotic to be approved in the US; retapamulin (Altabax), a 1% topical ointment for treatment of impetigo, was approved in 2007. 1 CABP is a leading cause of hospitalization and death in adults, especially the elderly. 2 Causative bacterial pathogens include Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Chlamydophila pneumoniae, and Legionella species.For outpatient treatment of CABP in otherwise healthy adults without recent antibiotic exposure, monotherapy with a macrolide such as azithromycin has been the regimen of choice, but rates of macrolide resistance among S. pneumoniae in parts of the US currently exceed 40%. Doxycycline is a reasonable alternative, but resistance to doxycycline is also increasing among S. pneumoniae. A respiratory fluoroquinolone (levofloxacin or moxifloxacin) is often used for adults with comorbidities or antibiotic exposure during the previous 90 days. These drugs can also be considered for otherwise healthy adults in areas where the rates of pneumococcal resistance to macrolides and doxycycline are Ն25%, but they can cause serious adverse effects. 3 Combining a beta-lactam (such as high-dose amoxicillin or cefpodoxime) with a macrolide or doxycycline is another option in areas with high rates of macrolide or doxycycline resistance. 4,5 For empirical treatment of CABP in hospitalized patients (not ICU), an antipneumococcal IV beta-lactam (such as ceftriaxone, cefotaxime, ceftaroline, or ampicillin/sulbactam) plus a macrolide (or doxycycline) or monotherapy with an IV respiratory fluoroquinolone (levofloxacin or moxifloxacin) is recommended. Omadacycline, a broad-spectrum IV and oral tetracycline recently approved for treatment of CABP, is an expensive alternative with limited data. 6 Addition of vancomycin or linezolid to standard treatment is recommended for patients at increased risk for methicillin-resistant S. aureus (MRSA). Short-course antibiotic therapy (5-7 days) is as effective as longer-course therapy for treatment of CABP.Lefamulin binds to the peptidyl transferase center of the 50S subunit of the bacterial ribosome, inhibiting bacterial protein synthesis. The probability of cross-resistance to beta-lactams, macrolides, fluoroquinolones, tetracyclines, or glycopeptides appears to be low. 7 Lefamulin is active in vitro and in vivo against S. pneumoniae, H. influenzae, M. pneumoniae, C. pneumoniae, Legionella pneumophila, and methicillin-susceptible strains of S. aureus (MSSA). It has in vitro activity against other streptococcal species, MRSA, Haemophilus parainfluenzae, and M. catarrhalis, but data establish-

Modern approaches to pharmacotherapy of Community-Acquired Pneumonia

“…Lefamulin is indicated for the treatment of bacterial infections caused by S. pneumoniae, S. aureus, H. influenzae, Legionella pneumophila, M. pneumoniae or Cl. Pneumoniae in adults (Lefamulin 2019c). Ceftaroline is the 5 th generation cephalosporin, which when compared with other cephalosporins is superior in activity against gram-positive bacteria, including multi-resistant strains of S. pneumoniae and MRSA (methicillin-resistant Staphylococcus aureus).…”