title: Comparative in vivo activity of gemifloxacin in a rat model of respiratory tract infection.
abstract: The in vivo efficacy of the novel quinolone gemifloxacin (SB-265805) was examined in a rat respiratory tract infection (RTI) model against four strains of Streptococcus pneumoniae and two strains of Haemophilus influenzae with varying susceptibilities to standard antimicrobial agents. Animals were infected intrabronchially to produce pneumonia and therapy with oral gemifloxacin, amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin or levofloxacin was started 24 h after infection. The doses administered were chosen to approximate in the rat the serum or tissue concentrations measured in humans following therapeutic dosing. Therapy continued once- or twice-daily for 3 days, and approximately 17 h after the end of therapy the lungs were excised for bacterial enumeration. Following infection with strains of S. pneumoniae, gemifloxacin produced a 3-5 log reduction in bacterial numbers compared with untreated animals. Gemifloxacin was as effective as amoxycillin- clavulanate, and was as potent or more potent than all other comparators. Notably, the quinolone agents trovafloxacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly less effective (P < 0.01) than gemifloxacin: these agents reduced bacterial numbers by < or =3 log compared with untreated animals. Gemifloxacin produced a marked response against H. influenzae infection, reducing bacterial numbers significantly (P < 0.01) compared with untreated controls. Gemifloxacin was significantly more potent than cefuroxime and azithromycin. None of the other comparator agents was more potent than gemifloxacin. The excellent efficacy seen in these experimental models of RTI with S. pneumoniae and H. influenzae confirms the in vitro activity of gemifloxacin against these organisms. This indicates that gemifloxacin may be of significant benefit in the treatment of RTI.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426-0989, USA. Valerie_Berry@SBPHRD.com
authors.forename: V
authors.initials: V
authors.lastname: Berry
authors.forename: R
authors.initials: R
authors.lastname: Page
authors.forename: J
authors.initials: J
authors.lastname: Satterfield
authors.forename: C
authors.initials: C
authors.lastname: Singley
authors.forename: R
authors.initials: R
authors.lastname: Straub
authors.forename: G
authors.initials: G
authors.lastname: Woodnutt
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D024841:Fluoroquinolones; D000077735:Gemifloxacin; D006192:Haemophilus Infections / Q000188:drug therapy*; D006193:Haemophilus influenzae / Q000187:drug effects*; D008297:Male; D009287:Naphthyridines / Q000627:therapeutic use*; D011008:Pneumococcal Infections / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012141:Respiratory Tract Infections / Q000188:drug therapy*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D000077735:Gemifloxacin