Comparative efficacy of gemifloxacin in experimental models of pyelonephritis and wound infection

Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spec trum antimicrobial activity. In this study, the efficacy of gemifloxacin wa s studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Grampositive wound infection re sulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylo coccus aureus. Gemifloxacin activity against these pathogens was compared w ith those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromyc in, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treat ment was initiated 1 h after infection and continued once or twice daily fo r 3 days. Around 17 h after the end of treatment, animals were killed and t he infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microor ganism), gemifloxacin reduced bacterial numbers significantly (P< 0.01) com pared with no treatment. No comparator agent had a greater effect than gemi floxacin. Notably, grepafloxacin and azithromycin were significantly less e ffective (P < 0.01) than gemifloxacin against E. coli pyelonephritis, and a moxycillin-clavulanate, azithromycin and trovafloxacin were inferior (P < 0 .01) against P. mirabilis infection. In the S. pyogenes wound infection mod el, gemifoxacin, amoxycillin-clavulanate, cefuroxime and azithromycin reduc ed bacterial numbers significantly compared with controls (Pe 0.01). Result s for the comparator quinolones were not significantly different from untre ated controls (P> 0.05). Gemifloxacin was also effective against staphyloco ccal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin , trovafloxacin and tosufloxacin were significantly less effective against these pathogens than gemifloxacin (P ( 0.01). No comparator agent had great er activity than gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of gemifloxacin in the treatme nt of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.