Combined Activity of Sulfamethoxazole, Trimethoprim, and Polymyxin B Against Gram-Negative Bacilli

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Abstract
The activity of the three two-drug combinations of sulfamethoxazole (SMX), trimethoprim (TMP), and polymyxin B (PB) against 52 clinical isolates of gram-negative bacilli was studied by a “checkerboard” agar dilution method. The organisms studied included strains of Enterobacter spp., Klebsiella pneumoniae, Serratia marcescens, Providence, Proteus , and Pseudomonas aeruginosa . The majority of these isolates were resistant to at least two of the three agents used in the combined studies and to the most commonly used antimicrobials. The TMP-PB combination demonstrated enhanced activity more frequently than the other two-drug combinations, showing synergism or addition in 85% of the combined studies; indifference or antagonism was also observed least frequently with TMP-PB. The great majority (83%) of Enterobacter-Klebsiella-Serratia isolates were susceptible to enhanced activity of all combinations. Proteus-Providence isolates were frequently susceptible (63%), but combined activity was indifferent or antagonistic against 60% of P. aeruginosa . Twelve isolates were selected for “killing-curve” assays in which an inoculum was incubated with SMX, TMP, and PB individually and in various two- and three-drug combinations. Surviving bacteria were counted at timed intervals over 24 h of incubation. The triple combination (SMX-TMP-PB) was synergistic against 9 of 12 isolates, whereas TMP-PB and SMX-PB showed synergism against 5 and 3 isolates, respectively. These data suggest that, although TMP-PB will often show enhanced activity against the gram-negative bacilli studied here, optimal antibacterial activity will be demonstrated when the three-drug combination is used.