BACKGROUND: Neomycin sulfate, bacitracin, and polymyxin B sulfate have been combined in topical preparations to provide a complementary antimicrobial spectrum for the prevention of minor wound infections. The advisability of the inclusion of neomycin sulfate has been questioned since it may cause contact sensitization. METHODS: To assess the value of neomycin, microdilution checkerboard titrations were used to determine the in vitro interactions between two-antibiotic and three-antibiotic combinations against reference strains of bacteria commonly associated 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. aureus and Ps. aeruginosa; neomycin/polymyxin B was synergistic for E. faecalis, and the bacitracin/polymyxin B combination was synergistic against Ps. aeruginosa. A three-drug combination of neomycin/bacitracin/polymyxin B had FIC values of < 1 for all organisms, indicating synergy and substantiating the clinical role of neomycin sulfate in current topical formulations. RESULTS: Neomycin has the lowest safety profile of the drugs in this combination. A replacement agent should ideally have similar or superior synergistic capabilities with the remaining drugs and contribute to the therapeutic efficacy of the preparation. Additionally, because of the strongly synergistic tendencies displayed by the three-drug combination, it may be possible to reduce the antibiotic concentrations present in current formulations. CONCLUSION: By developing this concept, there is potential for the formulation of topical preparations to be based on a sound theoretical and clinical rationale.
BACKGROUND:Neomycin sulfate, bacitracin, and polymyxin B sulfate have been combined in topical preparations to provide a complementary antimicrobial spectrum for the prevention of minor wound infections. The advisability of the inclusion of neomycin sulfate has been questioned since it may cause contact sensitization. METHODS: To assess the value of neomycin, microdilution checkerboard titrations were used to determine the in vitro interactions between two-antibiotic and three-antibiotic combinations against reference strains of bacteria commonly associated 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. aureus and Ps. aeruginosa; neomycin/polymyxin B was synergistic for E. faecalis, and the bacitracin/polymyxin B combination was synergistic against Ps. aeruginosa. A three-drug combination of neomycin/bacitracin/polymyxin B had FIC values of < 1 for all organisms, indicating synergy and substantiating the clinical role of neomycin sulfate in current topical formulations. RESULTS:Neomycin has the lowest safety profile of the drugs in this combination. A replacement agent should ideally have similar or superior synergistic capabilities with the remaining drugs and contribute to the therapeutic efficacy of the preparation. Additionally, because of the strongly synergistic tendencies displayed by the three-drug combination, it may be possible to reduce the antibiotic concentrations present in current formulations. CONCLUSION: By developing this concept, there is potential for the formulation of topical preparations to be based on a sound theoretical and clinical rationale.
Authors: Jennifer Brennan; Lalit Jain; Sofia Garman; Ann E Donnelly; Erik Scott Wright; Kevin Jamieson Journal: PLoS Comput Biol Date: 2022-07-18 Impact factor: 4.779