Staphylococcus aureus is noted for its clinical spectrum of disease ranging from asymptomatic colonisation to overwhelming sepsis and death and for its ability to become resistant to antibiotics. Resistance to beta-lactams, methicillin resistance, was first described 50 years ago, becoming a clinical problem in hospitals in the 1970s and the community in the 1990s. MRSA strains that originated in hospitals are usually also resistant to most of the non-beta-lactams as well, leaving vancomycin as

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... the main parenteral drug to treat serious MRSA infections, with the role of new drugs like daptomycin and linezolid not well defined. MRSA strains can exhibit low-level resistance to vancomycin (vancomycin-intermediate S. aureus [VISA]), probably due to a thickened cell wall, which results in the trapping of vancomycin away from the active site of the septum in dividing cells. Detecting this resistance is difficult as multiple genetic pathways lead to this resistance, obviating a molecular test, forcing reliance on phenotypic tests, all of which have issues with sensitivity, specificity and cost. Mortality of bloodstream infection correlates with vancomycin MIC so in this situation the MIC should be determined by Etest or microbroth dilution especially if endocarditis is present. Detection of resistant subpopulations (heterogeneous vancomycin-intermediate S. aureus [hVISA]) can be done with the expensive and time-consuming population analysis profile (PAP) but it is unclear if this confers additional therapeutic information. Types of vancomycin resistance in Staphylococcus aureus There are two essential types of reduced vancomycin susceptibility in S. aureus: (1) that conferred by cell wall thickening resulting in a small rise in the MIC and/or the presence of subpopulations with a modestly elevated MIC 1 ; and (2) that conferred by horizontal gene transfer of the vanA gene complex from vancomycin-resistant enterococci (VRE) to S. aureus, causing a more marked rise in the vancomycin MIC and clinical failure 2 . The Clinical and Laboratory Standards Institute (CLSI) reduced the breakpoints for vancomycin resistance in 2006 in response to the evidence that modest elevations of MIC were associated with a reduced likelihood of clinical response, and currently define vancomycin-susceptible S. aureus (VSSA) strains as having a MIC 4 mg/L, VISA as having MICs 4-8mg/L, and vancomycin-resistant S. aureus (VRSA) strains as having an MIC 16 1 . The European Committee on Antimicrobial Susceptibility Testing (EUCAST) defines VSSA as strains with an MIC 2 and VRSA as having an MIC 4, with no intermediate division 1 . The first described clinical isolate of VISA was the so-called 'Mu50' strain, isolated from a child with an MRSA sternotomy infection that failed to respond to vancomycin but responded to debridement and arbekacin plus ampicillin/sulbactam; the microbroth vancomycin MIC was 8 mg/L 3 . Mu50 and subsequent VISA isolates exhibit common characteristics (Figure 1) 1 . They grow more slowly than VSSA, exhibit pleomorphic colonial morphology, have reduced or delayed coagulase, demonstrate thickened cell walls on electron microscopy, have alterations in cell wall metabolism, reduced susceptibility to lysostaphin and decreased autolysis. hVISA strains usually have a vancomycin MIC in the CLSI and EUCAST susceptible ranges but possess subpopulations with a raised MIC, detectable by performing a PAP, where serial 10-fold dilutions of a suspension of S. aureus are plated on a series of agar plates containing increasing dilutions of vancomycin 1 . This was first described by Hiramatsu's group on the so-called 'Mu3' strain 4 , and Wootton et al. refined this by using a series of plates with doubling concentrations of vancomycin and serial 10-fold dilutions of the inocula with Mu3 as the control, generating the categories of VSSA (PAP-AUC ratio test: Mu3 <0.9), hVISA (ratio 0.9-1.35) and VISA (ratio >1.35) (Figure 2) 5 . Just over a dozen patients to date have had MRSA isolated that possess the vanA gene complex 2 . Most are US origin; none have been reported from Australasia to date. The US patients are older with multiple co-morbidities, were colonised with vanA VRE and