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Antimicrobial activity of the novel polymyxin derivative NAB739 tested against Gram-negative pathogens

Martti Vaara1, Helio S Sader, Paul R Rhomberg

  • 1Northern Antibiotics Ltd, FI-00720 Helsinki, Finland. martti.vaara@northernantibiotics.com

The Journal of Antimicrobial Chemotherapy
|November 9, 2012
PubMed
Abstract

Insights

NAB739 shows reduced activity against Gram-negative bacteria compared to polymyxin B, especially for non-susceptible strains. This novel polymyxin analogue may offer an alternative despite lower potency.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Polymyxins are last-resort antibiotics for multidrug-resistant Gram-negative infections.
  • Nephrotoxicity is a significant concern with polymyxin use.
  • NAB739 is a novel polymyxin analogue with structural modifications to its peptide portion.

Purpose of the Study:

  • To compare the in vitro antibacterial activity of NAB739 and polymyxin B.
  • To evaluate NAB739 against a collection of contemporary Gram-negative bacterial clinical isolates.
  • To assess the efficacy of NAB739 in polymyxin-susceptible and non-susceptible strains.

Main Methods:

  • Minimum Inhibitory Concentrations (MICs) were determined for 310 clinical isolates.
  • Reference broth microdilution method followed CLSI guidelines (M07-A9, 2012).
  • Bacterial species included Escherichia coli, Klebsiella pneumoniae, Acinetobacter spp., and Pseudomonas aeruginosa.

Main Results:

  • NAB739 MIC(90) values for susceptible E. coli and K. pneumoniae were 2 mg/L and 2 mg/L, respectively.
  • NAB739 MIC(90) values for susceptible Acinetobacter spp. and P. aeruginosa were 8 mg/L and 16 mg/L, respectively.
  • For non-susceptible strains, NAB739 MIC(90) was ≥ 64 mg/L, higher than polymyxin B.

Conclusions:

  • NAB739 demonstrated lower potency than polymyxin B against susceptible Gram-negative bacteria.
  • NAB739 showed significantly higher MIC(90) values against polymyxin-non-susceptible strains.
  • NAB739's modified structure impacts its antibacterial spectrum and potency.

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