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.