In vitro activity of a cecropin A-melittin antimicrobial peptide hybrid vs. multidrug-resistant strains of Acinetobacter baumannii prevalent in the UK
Abstract number: P569
Wareham D., Khanna P., Kamysz W.
Objectives:Acinetobacter baumannii has emerged as an important nosocomial pathogen causing burn wound infections, ventilator associated pneumonia, bacteraemia and sepsis in the critically ill. The organism exhibits formidable multi-drug resistance with the commonest isolates in the UK (OXA-23 clone 1) exhibiting resistance to all b-lactams (including carbapenems), b-lactam / inhibitor combinations, quinolones, and aminoglycosides. In view of the lack of agents in development for the treatment of MDR Acinetobacters we set out to determine the in-vitro activity of a hybrid of two antimicrobial peptides, cecropin A and melittin (CAMEL) versus a collection of recent clinical isolates and determine the killing kinetics versus the OXA-23 (1) strain.
Methods: A 15 residue peptide based on residues 17 of cecropin A and residues 29 of melittin was synthesised using fmoc chemistryand purified by solid phase extraction. Sixty-six consecutive clinical isolates, identified as A. baumannii by API 20NE and confirmed by specific PCR for the OXA-51 gene were obtained. Inhibitory and bactericidal concentrations of CAMEL peptide were determined by microtitre dilution using according to standard BSAC methodology. Time-kill assays using Camel peptide at 1 X and 2 X the MIC were performed on a representative isolate of OXA-23 clone 1.
Results: The MIC50 of Camel peptide was 8 mg/L and the MIC90 16 mg/L with a range of 432 mg/L. The MBC50 and MBC90 were 16 and 32 mg/L respectively (range 864 mg/L). In time kill assays Camel was rapidly bactericidal within 2 hrs. At 2 × MIC >3-fold log reductions in CFU/ml were sustained over 24 hrs.
Conclusions: CAMEL peptide exhibited promising activity versus prevalent strains of multidrug resistant A. baumannii and was rapidly bactericidal versus the OXA-23 clone 1 of A. baumannii. Further studies to determine in vivo stability, bioavailability and toxicity towards eukaryotic cells are needed to enable further development of this novel compound.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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