Globally, Staphylococcus aureus (S. aureus), notably methicillin-resistant S. aureus, is a leading cause of morbidity and mortality. Vancomycin is considered a drug of last resort for severe MRSA and other resistant Gram-positive infections. Vancomycin enjoyed a high level of success for decades following MRSA outbreaks until recent reports of increasing S. aureus MICs culminating in high-level vancomycin-resistant S. aureus (VRSA), first reported in 2002. Since then, there have been selected case reports of VRSA disease in the US and other countries. The resistance mechanism of VRSA is mediated by the VanA operon carried on the mobile genetic element Tn1546 acquired from vancomycin-resistant Enterococcus; co-infections with VRE have occurred in all cases. There has been no documented person to person VRSA transmission. The prolonged interval between exposure to vancomycin and VRSA development and the limited number of cases are reassuring; whether this translates to the needed extended period of clinical quiescence before a global epidemic is unknown. According to the World Health Organization (WHO), S. aureus pathogenicity and resistance patterns pose a significant threat to human health worldwide; MRSA, vancomycin intermediate-resistant S. aureus (VISA) and VRSA are currently classified as bacteria of high priority with potential to cause significantly devastating worldwide mortality in the absence of effective containment and therapeutic solutions. There are limited choices of drugs that are effective against VRSA; several promising therapeutic options are in research and development phases. VISA and VRSA have also been isolated in animal husbandry from pigs, goats, and cattle.

We review VRSA history and evolution, clinical spectrum and management. We also speculate on future trends.