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. 1994 Feb;38(2):374–377. doi: 10.1128/aac.38.2.374

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

I Ofek 1, S Cohen 1, R Rahmani 1, K Kabha 1, D Tamarkin 1, Y Herzig 1, E Rubinstein 1
PMCID: PMC284461  PMID: 8192470

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.

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Selected References

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  1. Athamna A., Ofek I., Keisari Y., Markowitz S., Dutton G. G., Sharon N. Lectinophagocytosis of encapsulated Klebsiella pneumoniae mediated by surface lectins of guinea pig alveolar macrophages and human monocyte-derived macrophages. Infect Immun. 1991 May;59(5):1673–1682. doi: 10.1128/iai.59.5.1673-1682.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bauer A. W., Kirby W. M., Sherris J. C., Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966 Apr;45(4):493–496. [PubMed] [Google Scholar]
  3. Danner R. L., Joiner K. A., Rubin M., Patterson W. H., Johnson N., Ayers K. M., Parrillo J. E. Purification, toxicity, and antiendotoxin activity of polymyxin B nonapeptide. Antimicrob Agents Chemother. 1989 Sep;33(9):1428–1434. doi: 10.1128/aac.33.9.1428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Duwe A. K., Rupar C. A., Horsman G. B., Vas S. I. In vitro cytotoxicity and antibiotic activity of polymyxin B nonapeptide. Antimicrob Agents Chemother. 1986 Aug;30(2):340–341. doi: 10.1128/aac.30.2.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kuehne R. W. Rapid determination of log10 50% lethal doses or 50% infective doses. J Clin Microbiol. 1983 Apr;17(4):702–703. doi: 10.1128/jcm.17.4.702-703.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lam C., Hildebrandt J., Schütze E., Wenzel A. F. Membrane-disorganizing property of polymyxin B nonapeptide. J Antimicrob Chemother. 1986 Jul;18(1):9–15. doi: 10.1093/jac/18.1.9. [DOI] [PubMed] [Google Scholar]
  7. Søgaard H. The pharmacodynamics of polymyxin antibiotics with special reference to drug resistance liability. J Vet Pharmacol Ther. 1982 Dec;5(4):219–231. doi: 10.1111/j.1365-2885.1982.tb00437.x. [DOI] [PubMed] [Google Scholar]
  8. Vaara M. Agents that increase the permeability of the outer membrane. Microbiol Rev. 1992 Sep;56(3):395–411. doi: 10.1128/mr.56.3.395-411.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Vaara M., Vaara T. Polycations as outer membrane-disorganizing agents. Antimicrob Agents Chemother. 1983 Jul;24(1):114–122. doi: 10.1128/aac.24.1.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Vaara M., Vaara T. Polycations sensitize enteric bacteria to antibiotics. Antimicrob Agents Chemother. 1983 Jul;24(1):107–113. doi: 10.1128/aac.24.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Vaara M., Vaara T. Sensitization of Gram-negative bacteria to antibiotics and complement by a nontoxic oligopeptide. Nature. 1983 Jun 9;303(5917):526–528. doi: 10.1038/303526a0. [DOI] [PubMed] [Google Scholar]
  12. Viljanen P., Vaara M. Susceptibility of gram-negative bacteria to polymyxin B nonapeptide. Antimicrob Agents Chemother. 1984 Jun;25(6):701–705. doi: 10.1128/aac.25.6.701. [DOI] [PMC free article] [PubMed] [Google Scholar]

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