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Northern Antibiotics Presents New Data on Novel Polymyxin Compounds at the Joint ICAAC/IDSA 2008
Date:10/28/2008

HELSINKI, October 28 /PRNewswire/ -- Northern Antibiotics Ltd., the developer of novel polymyxin derivatives for the treatment of infections caused by multidrug-resistant Gram-negative bacteria, revealed today animal efficacy and pharmacokinetic data from their NAB compounds at the 48th Annual ICAAC/IDSA 46th Annual Meeting in Washington, DC.

Northern Antibiotics has developed two series of novel polymyxin (NAB) compounds (Vaara M. et al., 2008, Antimicrob. Agents Chemother. 52:3229). The compounds of the first series (lead compound, NAB739) are directly antibacterial against polymyxin-susceptible Gram-negative enteric bacteria such as Escherichia coli, Klebsiella spp, and Enterobacter spp., as well as against Acinetobacter baumannii. The representatives of the second series (lead compound, NAB7061) have only a weak direct action but sensitize in a very remarkable degree these Gram negative bacteria to antibiotics such as macrolides, rifampin, and others. The compounds of both series carry only three positive charges whereas the notoriously nephrotoxic old polymyxins (colistin, polymyxin B) carry a total of five positive charges.

The in vivo efficacy of NAB739 and NAB7061 was evaluated in a murine peritoneal infection model using the virulent, encapsulated E. coli strain IH3080 (K1:O18) as the challenge organism. As low a dose as 1 mg/kg (body weight) of NAB739, given at 1h postinfection and repeated at 3 h postinfection, displayed potent bactericidal effect. The bacterial counts in the treated animals were 4.8 log10 lower in the mice treated with NAB739 than in the untreated control mice.

Furthermore, while NAB7061 (5 mg/kg) alone as well as erythromycin (20 mg/kg) alone were ineffective in the murine peritoneal model, the bacterial counts in mice that received their combination were 2.9 log10 lower than in the untreated controls (dosing time schedule as above with NAB739). Accordingly, the in vivo efficacy studies corroborate the previo
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