title: Activity of garenoxacin, an investigational des-F(6)-quinolone, tested against pathogens from community-acquired respiratory tract infections, including those with elevated or resistant-level fluoroquinolone MIC values.
abstract: Garenoxacin, a novel des-F(6)-quinolone, was tested against 40423 pathogenic isolates associated with community-acquired respiratory tract infections (CA-RTIs). The strains included Streptococcus pneumoniae (18887), Haemophilus influenzae (15555), and Moraxella catarrhalis (5981), each isolated from a significant infection monitored by the SENTRY Antimicrobial Surveillance Program (1999-2005; North America, Latin America, and Europe). All tests were performed by reference broth microdilution methods for garenoxacin and 19 comparison agents. The garenoxacin MIC(90) and percentage (%) of strains inhibited at < or =1 microg/mL (proposed susceptible breakpoint) were S. pneumoniae (0.06 microg/mL, >99.9% susceptible), H. influenzae (< or =0.03 microg/mL, >99.9%), and M. catarrhalis (< or =0.03 microg/mL, 100.0%). The garenoxacin potency versus the pneumococci was 16- to 32-fold greater than levofloxacin or ciprofloxacin and 2-fold superior to moxifloxacin (MIC(90), 0.12 microg/mL). Resistances to other classes of antimicrobials did not adversely influence garenoxacin MIC results. Ciprofloxacin- or levofloxacin-resistant (MIC, > or =4 microg/mL) S. pneumoniae had higher garenoxacin MIC(90) values (1 microg/mL), but 90.6% to 97.5% of strains remained susceptible. Strains of all 3 monitored pathogens with mutations in the quinolone resistance determining region (QRDR) had higher garenoxacin MIC results, with > or =3 to 4 QRDR mutations required to elevate garenoxacin MIC values to > or =2 microg/mL. In conclusion, garenoxacin possesses a potent activity against pneumococci, H. influenzae, and M. catarrhalis strains worldwide, at a level significantly greater than the available tested agents in the fluoroquinolone class (ciprofloxacin, levofloxacin, and moxifloxacin). Only 13 and 4 isolates (0.07% and 0.03%) of S. pneumoniae and H. influenzae, respectively, had a garenoxacin MIC at > or =2 microg/mL, thus, making this new "respiratory antipneumococcal" quinolone an attractive candidate for the therapy of contemporary CA-RTI (bronchitis, pneumonia, and sinusitis).
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA. ronald-jones@jmilabs.com
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fritsche
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Stilwell
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017714:Community-Acquired Infections / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D001936:Moraxella catarrhalis / Q000187:drug effects*; D012141:Respiratory Tract Infections / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C419689:garenoxacin