Methicillin-resistant Staphylococcus aureus replication in the presence of high (≥32 µg/ml) drug concentration of vancomycin as seen by electron microscopy

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has unfortunately become a common pathogen in many healthcare facilities. In many institutions, vancomycin remains the preferred agent for treating serious MRSA infections including bacteraemia with or without endocarditis. The mutant prevention concentration (MPC) testing ≥10⁹ colony forming units of bacteria, describes the antimicrobial drug concentration blocking the growth of the least susceptible cell from high density bacterial populations. With blood culture isolates of MRSA, we discovered strains with MPC values ≥32 µg/ml and viable cells could be readily recovered from agar plates containing 32 µg/ml of vancomycin. To investigate MRSA strains surviving in high concentrations of vancomycin on drug containing agar plates, we utilized electron microscopy to measure cell wall thickness as this has been previously reported as a potential mechanism of resistance¹ along with septum thickening. Our data shows MRSA replication from high density bacterial populations in the presence of ≥32 µg/ml of vancomycin. Such observations may explain vancomycin failure in some patients and/or persistent bacteraemia and could potentially question the use of this drug in some critically ill patients in favour of an alternative agent.

Keywords: MPC; MRSA; electron microscopy; vancomycin.