Despite introduction in 1958, vancomycin resistance in clinical Staphylococcus aureus isolates was not reported until 1997, when a Japanese patient with a sternotomy infection failed vancomycin. The isolate, Mu50, had an MIC of 8mg/L (vancomycin-intermediate S. aureus [VISA]). Mu3 was isolated in 1996 from a patient with pneumonia failing vancomycin therapy; this isolate had an MIC of 4mg/L but subpopulations with higher MICs, “heterogeneous” VISA (hVISA).
Differing definitions of VISA and hVISA make the literature challenging. hVISA prevalence varies – 20% of tertiary hospitals in the original Mu3 paper, but another Japanese group failed to detect it. hVISA/VISA phenotypes have been described in Oceania, North America, Asia and Europe. Risk factors for hVISA/VISA acquisition are exposure to vancomycin, renal failure, diabetes, malignancy, surgery and high bacterial load infections. Some patients develop hVISA/VISA on vancomycin therapy; DNA fingerprinting shows isolates are indistinguishable; outbreaks of hVISA/VISA are also described. Some but not all centres have shown vancomycin MICs increased over time, “MIC creep”; this phenomenon appears to be method-dependant. hVISA/VISA cells have a thickened cell wall; this observation led to the “affinity trapping” hypothesis: diffusion of vancomycin to its active site in the cell division septum is reduced.
Various mutations have been detected in hVISA/VISA strains; unfortunately a common mutation has not been identified, precluding a molecular test. WGS has confirmed this and added to the mystery. Detection remains phenotypic. Colonial morphology changes (mixed size and colour) are typical. Commercial systems have difficulty categorising hVISA/VISA. The population analysis profile is currently the “gold standard” test. Agar dilution, Etest MIC and microbroth MIC tests give different results detecting VISA, but higher MICs are associated with “clinical failures”, and the proportion of isolates that are hVISA rises as MIC rises past 1.5mg/L. hVISA is more difficult to detect – the usual screening test is the macromethod Etest, with a sensitivity of 69-98% and specificity of 89-94%. Various laboratory approaches about when to test and how to test will be discussed.
VRSA, where S. aureus is highly resistant to vancomycin due to horizontal gene transfer from VRE, remains incredibly rare and essentially confined to the USA, despite global profligate use of glycopeptides in humans and animals and high level endemic VRE throughout the world. The reasons for this will be discussed.