Antibiotic combinations significantly more active than monotherapy in an in vitro infection model of Stenotrophomonas maltophilia

The goal of this study was to investigate clinical doses of trimethoprim-sulfamethoxazole (TMP-SMX) alone and in combination against Stenotrophomonas maltophilia in an in vitro pharmacodynamic infection model. A I-compartment model was established using 4 clinical isolates of S. maltophilia susceptible to TMP-SMX and susceptible or intermediately susceptible to at least one other agent (ie, ceftazidime, ciprofloxacin, gentamicin, tobramycin). Antibiotics alone and in combination were tested by simulating unbound serum concentration profiles achieved with multiple-dose regimens in humans. Despite susceptible minimum inhibitory concentrations, TMP-SMX alone was bacteriostatic at best against all isolates. All antibiotic combinations were more active than monotherapy as determined by bacteria] reductions at both 24 and 48 It (P < 0.0001). Significant benefit was observed even with agents inactive alone or only intermediately susceptible based on minimum inhibitory concentrations. These preclinical data support further investigation of antibiotic combinations in the management of serious S. maltophilia infections. (C) 2005 Published by Elsevier Inc.