title: NXL-103, a combination of flopristin and linopristin, for the potential treatment of bacterial infections including community-acquired pneumonia and MRSA.
abstract: Novexel is developing the novel, orally active, semisynthetic streptogramin NXL-103, which has potential therapeutic application in the treatment of community-acquired pneumonia, community- or hospital-acquired MRSA, vancomycin-resistant enterococcus, and acute bacterial skin and soft tissue infections. NXL-103 is a combination of streptogramin A:streptogramin B components, initially developed in a 70:30 dose ratio. In multiple in vitro studies, NXL-103 demonstrated potent activity against different types of bacteria, such as Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecium, Enterococcus faecalis, Haemophilus influenzae and Haemophilus parainfluenzae. NXL-103 was not affected by the resistance profiles of bacteria against other commonly used antibiotics. In phase I clinical trials, NXL-103 achieved bactericidal levels in plasma and was generally well tolerated, with side effects primarily on the gastrointestinal system. The first phase II trial conducted to evaluate the efficacy of NXL-103 against community-acquired pneumonia revealed that the compound was comparable with amoxicillin. NXL-103 has promise to become an important agent in the treatment of community-acquired pneumonia and complex skin and soft tissue infections, pending further development.
authors.affiliation: University of Virginia Health System, Department of Surgery, Box 800709, Charlottesville, VA 22908-0709, USA.
authors.forename: Amani D
authors.initials: AD
authors.lastname: Politano
authors.forename: Robert G
authors.initials: RG
authors.lastname: Sawyer
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D002986:Clinical Trials as Topic; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000382:microbiology; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D004338:Drug Combinations; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D025364:Streptogramin A / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D025381:Streptogramin B / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; C509060:flopristin, linopristin drug combination; D025381:Streptogramin B; D025364:Streptogramin A