Antimicrobial characterisation of CEM-101 activity against respiratory tract pathogens, including multidrug-resistant pneumococcal serogroup 19A isolates

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 (MLS_B)–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)=0.25mg/L; highest MIC at 0.5mg/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=0.5mg/L). CEM-101 was the most potent antimicrobial agent tested against L. pneumophila, with all MIC values at ≤0.015mg/L (telithromycin MIC90=0.03mg/L). CEM-101 was as potent as azithromycin against Haemophilus spp. RTI pathogens (MIC90=2mg/L), with no variations for β-lactamase production. CEM-101 MIC values against M. catarrhalis were all at ≤0.5mg/L. Interestingly, CEM-101 potency was ca. 6log₂ dilutions greater than telithromycin MIC results among 44 β-haemolytic streptococci having telithromycin MICs ≥2mg/L. CEM-101 exhibited the greatest potency and widest spectrum of activity against RTI pathogens among the tested MLS_B–ketolide agents (azithromycin, clarithromycin, erythromycin, telithromycin, clindamycin and quinupristin/dalfopristin) and was comparable overall with levofloxacin.

Keywords: CEM-101, Ketolide, Streptococcus pneumoniae, Community-acquired bacterial pneumonia, Antimicrobial resistance