Comparative in vivo activity of gemifloxacin in a rat model of respiratorytract infection

The in vivo efficacy of the novel quinolone gemifloxacin (SB-265805) was ex amined in a rat respiratory tract infection (RTI) model against four strain s of Streptococcus pneumoniae and two strains of Haemophilus influenzae wit h varying susceptibilities to standard antimicrobial agents. Animals were i nfected intrabronchially to produce pneumonia and therapy with oral gemiflo xacin, amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, tr ovafloxacin, 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. The rapy continued once- or twice-daily for 3 days, and approximately 17 h afte r the end of therapy the lungs were excised for bacterial enumeration. Foll owing infection with strains of S. pneumoniae, gemifloxacin produced a 3-5 log reduction in bacterial numbers compared with untreated animals. Gemiflo xacin was as effective as amoxycillin-clavulanate, and was as potent or mor e potent than all other comparators. Notably, the quinolone agents trovaflo xacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly les s effective (P < 0.01) than gemifloxacin: these agents reduced bacterial nu mbers by less than or equal to 3 log compared with untreated animals. Gemif loxacin produced a marked response against ii. influenzae infection, reduci ng bacterial numbers significantly (P < 0.01)compared with untreated contro ls. Gemifloxacin was significantly more potent than cefuroxime and azithrom ycin. None of the other comparator agents was more potent than gemifloxacin . The excellent efficacy seen in these experimental models of RTI with S. p neumoniae and H. influenzae confirms the in vitro activity of gemifloxacin against these organisms. This indicates that gemifloxacin may be of signifi cant benefit in the treatment of RTI.