In vivo bactericidal effect of a new proline-rich peptide A3-APO on an ESBL-producing Escherichia coli strain
Abstract number: O488
Rozgonyi F., Nagy K., Szabó D., Anderlik P., Kocsis B., Ötvös L.
Objectives: The aim of this study was to examine the in vivo efficacy of a new proline-rich antibacterial peptide A3-APO previously proved to be in vitro bactericidal on some enteric bacterial strains.
Methods: CD-1 female mice of 1520 g were pretreated with 18 mg/kg cisplatin for 3 days to impair kidney clearance similar to that of human. Then they were challenged intraperitoneally (ip) with 108 CFU per g mouse of an extended-spectrum b-lactamase producing E. coli strain. Four, 8 and 12 hours after challenge 40 mg/kg imipenem, 10, 20 and 40 mg/kg A3-APO were administered to 10 mice of each concentration of the antimicrobials. Prior to drug administration, blood was taken from the tail vein of 35 mice either the infected and untreated or the infected and treated groups for determining blood bacterial counts.
Results: Blood bacterial counts amounted to 105 CFU/ml by the 4th hour of challenge and exceeded 107 CFU/ml by the 12th hour in the untreated mice. In contrast, each concentration of A3-APO decreased the blood bacterial level by two log10 units four hours after the 1st administration, e.g. from 105 to 103 CFU/ml similar to that after imipenem treatment. Continuous dosing of either the peptide or imipenem retained the blood bacterial counts at the lowest detectable levels.
Conclusion: To our knowledge, this is the first antibacterial peptide that is effective in mortality models of Gram-negative systemic infection and exerts bactericidal activity in vivo in doses comparable to traditional antibiotics without notable toxic side effects.
Supported by the Sbarro Health Research Organization and Hungarian OTKA T46186.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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