IN-VITRO INTERACTIONS OF NEOMYCIN SULFATE, BACITRACIN, AND POLYMYXIN-B SULFATE

Background. Neomycin sulfate, bacitracin, and polymyxin B sulfate have been combined in topical preparations to provide a complementary anti microbial spectrum for the prevention of minor wound infections. The a dvisability of the inclusion of neomycin sulfate has been questioned s ince it may cause contact sensitization. Methods. To assess the value of neomycin, microdilution checkerboard titrations were used to determ ine the in vitro interactions between two-antibiotic and three-antibio tic combinations against reference strains of bacteria commonly associ ated with wound infections. Using Fractional Inhibitory Concentration (FIC) indices (< 0.5 indicates synergism with two-drug combinations), the combination of neomycin/bacitracin was synergistic for both S. aur eus and Ps. aeruginosa; neomycin/polymyxin B was synergistic for E. fa ecalis, and the bacitracin/polymyxin B combination was synergistic aga inst Ps. aeruginosa. A three-drug combination of neomycin/bacitracin/p olymyxin B had FIC values of < 1 for all organisms, indicating synergy and substantiating the clinical role of neomycin sulfate in current t opical formulations. Results. Neomycin has the lowest safety profile o f the drugs in this combination. A replacement agent should ideally ha ve similar or superior synergistic capabilities with the remaining dru gs and contribute to the therapeutic efficacy of the preparation. Addi tionally, because of the strongly synergistic tendencies displayed by the three-drug combination, it may be possible to reduce the antibioti c concentrations present in current formulations. Conclusion. By devel oping this concept, there is potential for the formulation of topical preparations to be based on a sound theoretical and clinical rationale .