Combined activity of sulfamethoxazole, trimethoprim, and polymyxin B against gram-negative bacilli

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.