I. Ofek et al., ANTIBACTERIAL SYNERGISM OF POLYMYXIN-B NONAPEPTIDE AND HYDROPHOBIC ANTIBIOTICS IN EXPERIMENTAL GRAM-NEGATIVE INFECTIONS IN MICE, Antimicrobial agents and chemotherapy, 38(2), 1994, pp. 374-377
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.