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Updated: Jun 15, 2026
Intrarenal Injection of Escherichia coli in a Rat Model of Pyelonephritis
Published on: July 18, 2017
Novel polymyxin derivatives are effective in treating experimental Escherichia coli peritoneal infection in mice
Carina Vingsbo Lundberg1, Timo Vaara, Niels Frimodt-Møller
1National Center for Antimicrobials and Infection Control, Statens Serum Institut, Copenhagen S, DK-2300, Denmark.
Objectives:
Novel synthetic polymyxin derivatives including NAB737 and NAB739 are as effective as polymyxin B in vitro against the common opportunistic pathogen Escherichia coli. Another derivative, NAB7061, lacks direct antibacterial action but sensitizes E. coli to several other antibacterial agents including macrolides. The renal handling of NAB739 and NAB7061 in rats differs from that of polymyxin B. Furthermore, the affinities of NAB739 and NAB7061 for isolated rat kidney brush border membrane are significantly lower than that of polymyxin B. Here we investigate the in vivo antibacterial effect of these compounds.
Methods:
The polymyxin derivatives were evaluated in an experimental murine peritonitis model. Immunocompetent mice were infected intraperitoneally with E. coli IH3080 and were subcutaneously treated with NAB737, NAB739 or NAB7061.
Results:
A >4.0 log(10) reduction in bacterial load compared with saline control was achieved 6 h after initiation of treatment with 1 mg/kg of NAB739 twice or 4 mg/kg of NAB737 twice. Combination therapy with NAB7061 (5 mg/kg) twice and erythromycin (10 mg/kg) resulted during the same time course in a >2.0 log(10) reduction in bacterial load compared with saline control. Neither NAB7061 nor erythromycin was effective as monotherapy. Together with the ability to reduce bacterial load, the NAB compounds also improved the clinical status of the mice.
Conclusions:
We found that the three novel synthetic polymyxin B derivatives had a potent in vivo bactericidal effect against E. coli.
Insights
Novel polymyxin derivatives NAB737 and NAB739 show potent in vivo antibacterial effects against Escherichia coli. These synthetic compounds demonstrate significant bacterial load reduction in a murine peritonitis model.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Polymyxin B is a critical antibiotic for treating infections caused by Gram-negative bacteria like Escherichia coli.
- Novel synthetic polymyxin derivatives are being developed to improve efficacy and reduce toxicity.
- Previous in vitro studies showed some derivatives are effective against E. coli, with differing properties from polymyxin B.
Purpose of the Study:
- To evaluate the in vivo antibacterial efficacy of novel synthetic polymyxin derivatives against Escherichia coli.
- To assess the therapeutic potential of NAB737, NAB739, and NAB7061 in a relevant animal model.
Main Methods:
- A murine peritonitis model was used to test the efficacy of the polymyxin derivatives.
- Mice were infected with E. coli IH3080 and treated with subcutaneous injections of NAB737, NAB739, or NAB7061.
- Combination therapy with NAB7061 and erythromycin was also investigated.
Main Results:
- NAB739 and NAB737 achieved a >4.0 log(10) reduction in bacterial load at specific dosages.
- Combination therapy with NAB7061 and erythromycin resulted in a >2.0 log(10) reduction in bacterial load.
- The synthetic polymyxin derivatives improved the clinical status of infected mice.
Conclusions:
- The three novel synthetic polymyxin B derivatives exhibit potent in vivo bactericidal activity against E. coli.
- These compounds represent promising therapeutic agents for E. coli infections.
