GV005 Influence of quinupristin/dalfopristin on growth and exotoxin production of Staphylococcus aureus

Abstract

CEM-101 is a novel fluorinated macrolide–ketolide with potent activity against bacterial pathogens that are susceptible or resistant to other macrolide–lincosamide–streptogramin B (MLSB)–ketolide agents. CEM-101 is being developed for oral and parenteral use in moderate to moderately severe community-acquired bacterial pneumonia. The objective of this study was to assess the activity of CEM-101 and comparators against contemporary respiratory tract infection (RTI) isolates. A worldwide sample of organisms was used, including Streptococcus pneumoniae [n = 168; 59.3% erythromycin-resistant and 18 multidrug-resistant (MDR) serogroup 19A strains], Moraxella catarrhalis (n = 21; 11 β-lactamase positive), Haemophilus influenzae (n = 100; 48 β-lactamase positive), Haemophilus parainfluenzae and Haemophilus haemolyticus (n = 12), and Legionella pneumophila (n = 30). Testing and interpretation were performed using reference Clinical and Laboratory Standards Institute methods. CEM-101 was very potent against S. pneumoniae [minimum inhibitory concentration for 90% of the organisms (MIC90) = 0.25 mg/L; highest MIC at 0.5 mg/L] and was 2- and ≥32-fold more active than telithromycin and clindamycin, respectively. CEM-101 also demonstrated potent activity against S. pneumoniae MDR-19A strains (MIC90 = 0.5 mg/L). CEM-101 was the most potent antimicrobial agent tested against L. pneumophila, with all MIC values at ≤0.015 mg/L (telithromycin MIC90 = 0.03 mg/L). CEM-101 was as potent as azithromycin against Haemophilus spp. RTI pathogens (MIC90 = 2 mg/L), with no variations for β-lactamase production. CEM-101 MIC values against M. catarrhalis were all at ≤0.5 mg/L. Interestingly, CEM-101 potency was ca. 6 log2 dilutions greater than telithromycin MIC results among 44 β-haemolytic streptococci having telithromycin MICs ≥2 mg/L. CEM-101 exhibited the greatest potency and widest spectrum of activity against RTI pathogens among the tested MLSB–ketolide agents (azithromycin, clarithromycin, erythromycin, telithromycin, clindamycin and quinupristin/dalfopristin) and was comparable overall with levofloxacin.