1989 Volume 42 Issue 5 Pages 807-814
Combinations of L-658, 310 and an aminoglycoside or ciprofloxacin were tested against clinical isolates of Pseudomonas aeruginosa using a checkerboard broth dilution technique. Using the mean fractional bactericidal concentration of ≤0.5 as the criterion for synergy, the combinations L-658, 310/tobramycin and L-658, 310/ciprofloxacin against strains of P. aeruginosa resistant to the companion drug were synergistic. The data plotted as isobolograms showed synergy for all combinations tested. Synergy was clearly demonstrated in time-kill experiments. A greater than 3-log decrease in viable cell count for P. aeruginosa was seen after exposure for 24 hours to subinhibitory concentrations of the combined agents. In in vivo mouse models, the efficacy of L-658, 310 against experimental P. aeruginosa bacteremias was enhanced by the addition of a low dose of an aminoglycoside to the treatment regimen, thus confirming the synergy demonstrated in time-kill experiments.
