Reversing methicillin resistance in MRSA using a bacterial transforming agent

Abstract

Background: Antimicrobial resistance in staphylococci remains a significant problem in the clinical management of infections. New therapeutic entities are required for the prophylaxis and treatment of staphylococcal infection including those caused by methicillin-resistant Staphylococcus aureus (MRSA). Potential candidates include bacterial transforming agents (BTAs), compounds that can potentiate the activity of cell-wall-active antimicrobials by hypersensitizing the bacterial cell wall to the bactericidal effects of these drugs. BTAs have been found to inhibit MRSA in vitro when administered in combination with established antibiotics. Objectives: To examine the antimicrobial potential of a known BTA (BTA 19976a) on strains of MRSA in vitro. Methods: Etest and time-kill methodologies were employed to assess the inhibitory potential of BTA at 10% w/v on strains of E-MRSA-3, E-MRSA-15 and E-MRSA-16. Results: Etests demonstrated a reduction in the oxacillin MIC for E-MRSA-3, E-MRSA-15 and the NCTC 12493 reference strain of MRSA when exposed to BTA at 10% w/v. Time-kill assays similarly demonstrated a reduction in viable counts for organisms exposed to methicillin at 40 mg/L + BTA at 10% w/v, compared with methicillin alone, an effect which varied in cidality, pattern of killing and regrowth between strains. Conclusions: The antimicrobial effects of this BTA on MRSA are encouraging and warrant further investigation with large numbers of different epidemic strains and a comprehensive PK/PD evaluation. This could lead to new therapeutic entities for the prophylaxis and treatment of staphylococcal infections. © 2006 Oxford University Press.