Synergy of ciprofloxacin and azlocillin in vitro and in a neutropenic mouse model of infection

Abstract
Combinations of ciprofloxacin with azlocillin, piperacillin and ticarcillin were tested in vitro against clinical isolates. Azlocillin plus ciprofloxacin showed synergy against 30% of Pseudomonas aeruginosa isolates; it was either synergistic or additive against 78% of all isolates tested even those resistant to the beta-lactam. Synergism was rarely noted for Klebsiella pneumoniae, Escherichia coli, Enterobacter spp. or Branhamella spp. isolates. Minimum inhibitory concentrations of ciprofloxacin plus azlocillin, plus piperacillin and plus ticarcillin against Pseudomonas spp. were reduced 4 or 2 fold, respectively. However, the combination azlocillin plus ciprofloxacin showed primarily indifference against gram-positive strains. Neutropenic mice infected with a lethal challenge of Pseudomonas spp. were protected by a combination of azlocillin and ciprofloxacin. Its additive and/or synergistic effects and expanded spectrum of activity against streptococci, methicillin-resistant staphylococci and JK corynebacteria may provide an alternative to traditional therapy.