title: 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 beta-lactamase positive), Haemophilus influenzae (n=100; 48 beta-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 > or =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 < or = 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 beta-lactamase production. CEM-101 MIC values against M. catarrhalis were all at < or =0.5mg/L. Interestingly, CEM-101 potency was ca. 6 log(2) dilutions greater than telithromycin MIC results among 44 beta-haemolytic streptococci having telithromycin MICs > or = 2 mg/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.
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA. david-farrell@jmilabs.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Biedenbach
authors.forename: Paul R
authors.initials: PR
authors.lastname: Rhomberg
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D001424:Bacterial Infections / Q000382:microbiology*; D017714:Community-Acquired Infections / Q000382:microbiology*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D012141:Respiratory Tract Infections / Q000382:microbiology*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D014230:Triazoles; C547755:solithromycin