ANTIBACTERIAL SYNERGISM OF POLYMYXIN-B NONAPEPTIDE AND HYDROPHOBIC ANTIBIOTICS IN EXPERIMENTAL GRAM-NEGATIVE INFECTIONS IN MICE

Polymyxin B nonapeptide, derived by cleavage of the fatty acyl diamino butyric acid from polymyxin B, is considerably less toxic, lacks bacte ricidal activity, and retains its ability to render gram-negative bact eria susceptible to several antibiotics by permeabilizing their outer membranes. The peptide rendered all 53 polymyxin-susceptible strains t ested more susceptible to novobiocin, lowering the MIC of novobiocin e ightfold or more. The combination of polymyxin B nonapeptide with novo biocin or with erythromycin administered intraperitoneally in multiple doses synergistically protected mice infected with gram-negative bact eria. This combination may be clinically useful because of the apparen t rarity of the acquisition of resistance.