title: Antibiotic combinations significantly more active than monotherapy in an in vitro infection model of Stenotrophomonas maltophilia.
abstract: 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 1-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 bacterial reductions at both 24 and 48 h (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.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnepeg, MB, Canada R3T 2N2. zelenits@ms.umanitoba.ca
authors.forename: Sheryl A
authors.initials: SA
authors.lastname: Zelenitsky
authors.forename: Harris
authors.initials: H
authors.lastname: Iacovides
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ariano
authors.forename: Godfrey K M
authors.initials: GK
authors.lastname: Harding
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D020615:Stenotrophomonas maltophilia / Q000187:drug effects*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination