Using the checkerboard titration method as well as the time-kill curve technique, we investigated the activities of beta-lactams, fluoroquinolones, amikacin, and fosfomycin alone and in combination against Pseudomonas aeruginosa isolated from patients with complicated urinary tract infections. In the checkerboard titration studies, none of 21 combinations demonstrated antagonism against 26 strains tested, and the mean fractional inhibitory concentration (FIC) indices for these combinations ranged between 0.4694 and 0.9828. Corresponding to the respective FIC indices, the bactericidal activity determined in combinations of meropenem with ciprofloxacin or amikacin and ceftazidime with ciprofloxacin at sub-minimum inhibitory concentrations (MICs) produced a great reduction in bacterial counts (>/=2 log10 CFU/ml) within 6 h of administration against most of the strains, including strains resistant to one or both drugs, and these synergistic effects were confirmed morphologically by scanning electron microscopy. In time-lag combinations, the first administration of ciprofloxacin or amikacin supplemented by meropenem with 1-h lag diminished bactericidal activity, in comparison with the simultaneous administration of the drugs. These results suggest that simultaneous combinations of beta-lactams with fluoroquinolones or amikacin may be useful alternatives for the treatment of serious infections due to P. aeruginosa.