Antibacterial synergism of polymyxin B nonapeptide and hydrophobic antibiotics in experimental gram-negative infections in mice

I. Ofek*, S. Cohen, R. Rahmani, K. Kabha, D. Tamarkin, Y. Herzig, E. Rubinstein

*Corresponding author for this work

Research output: Contribution to journalComment/debate

93 Scopus citations

Abstract

Polymyxin B nonapeptide, derived by cleavage of the fatty acyl diaminobutyric acid from polymyxin B, is considerably less toxic, lacks bactericidal activity, and retains its ability to render gram-negative bacteria susceptible to several antibiotics by permeabilizing their outer membranes. The peptide rendered all 53 polymyxin-susceptible strains tested more susceptible to novobiocin, lowering the MIC of novobiocin eightfold or more. The combination of polymyxin B nonapeptide with novobiocin or with erythromycin administered intraperitoneally in multiple doses synergistically protected mice infected with gram-negative bacteria. This combination may be clinically useful because of the apparent rarity of the acquisition of resistance.

Original languageEnglish
Pages (from-to)374-377
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume38
Issue number2
DOIs
StatePublished - 1994

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