title: CEM-101, a novel fluoroketolide: antimicrobial activity against a diverse collection of Gram-positive and Gram-negative bacteria.
abstract: CEM-101 is a novel fluoroketolide with reported high potency against diverse groups of Gram-positive (Micrococcus spp., viridans group streptococci, Corynebacterium spp. Listeria monocytogenes, Clostridium spp., etc.) and Gram-negative bacteria (Neisseria gonorrhoeae, Campylobacter jejuni, Helicobacter pylori, Bacteroides fragilis, Shigella spp., etc.), including mycoplasma and ureaplasma, as well as bacteria commonly associated with community-acquired respiratory tract infections and skin and skin structure infections. In this study, CEM-101 and comparator antimicrobials were tested against a collection of very low prevalence aerobic and anaerobic bacteria collected via the SENTRY Antimicrobial Surveillance Program platform. CEM-101 was highly active against all Gram-positive organisms (MIC(50), 0.015 microg/mL) as compared with telithromycin (MIC(50), 0.06 microg/mL), clarithromycin (MIC(50), 0.12 microg/mL), and erythromycin (MIC(50), 0.25 microg/mL). Among Gram-negative pathogens, CEM-101 also displayed a high potency against most strains (MIC(50), 4 microg/mL) but was found to be equivalent or less active when compared with other antimicrobials tested with MIC(50) values ranging from < or =0.12 microg/mL for levofloxacin to 8 microg/mL for telithromycin. Among the strict anaerobic species, CEM-101 activity mirrored that of the aerobic species: high activity against the Gram-positive anaerobes (MIC(50) results ranging from < or =0.03 microg/mL to 0.12 microg/mL) and equivalent or less susceptible against Gram-negative anaerobes. Our in vitro antimicrobial susceptibility results for CEM-101 demonstrate better activity compared with other MLS(B) class agents among a diverse group of uncommonly isolated bacterial pathogens; these results provide an impetus for possible expanded indications during Phase 2 and 3 clinical trials.
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA. shan-putnam@jmilabs.com
authors.forename: Shannon D
authors.initials: SD
authors.lastname: Putnam
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Moet
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001420:Bacteria, Aerobic / Q000187:drug effects; D001421:Bacteria, Anaerobic / Q000187:drug effects; D001424:Bacterial Infections / Q000382:microbiology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D014230:Triazoles; C547755:solithromycin