Vancomycin-resistant Staphylococcus aureus refers to strains of Staphylococcus aureus that have become resistant to the glycopeptide antibiotic vancomycin. With the increase of staphylococcal resistance to methicillin, vancomycin (or another glycopeptide antibiotic, teicoplanin) is often a treatment of choice in infections with methicillin-resistant S. aureus (MRSA). Three classes of vancomycin-resistant S. aureus have emerged that differ in vancomycin susceptibilities: vancomycin-intermediate S. aureus (VISA), heterogenous vancomycin-intermediate S. aureus (hVISA), and high-level vancomycin-resistant S. aureus (VRSA).[1]
High-level vancomycin resistance in S. aureus has been rarely reported.[2] However, these strains may also be resistant to meropenem and imipenem, two other antibiotics that can be used in sensitive Staphylococcus strains.
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VISA was first identified in Japan in 1996 and has since been found in hospitals in the United Kingdom, France, the U.S., Asia, and Brazil. It is also termed GISA (glycopeptide-intermediate Staphylococcus aureus), indicating resistance to all glycopeptide antibiotics. These bacterial strains present a thickening of the cell wall, which is believed to reduce the ability of vancomycin to diffuse into the division septum of the cell required for effective vancomycin treatment.[3]
Even with the absence of high-level resistance to vancomycin, another concern posed by the presence of VISA is the increased difficulty in prescribing treatments, especially in situations where an effective treatment for an infection is needed urgently, before detailed resistance profiles can be obtained. In hospitals already endemic with multiresistant MRSA, the appearance of VRSA would make the treatment of infected patients much more difficult.
Ceftobiprole was found by Rockefeller University to be effective as of 2008. Linezolid, quinupristin/dalfopristin, daptomycin and tigecycline are treatments of consideration.
Clinical experience suggests that barriers exist to the evolution of endogenous vancomycin resistance in S. aureus, given occasional reports of low-level vancomycin resistance. However, in vitro and in vivo experiments reported in 1992 demonstrated that vancomycin resistance genes from Enterococcus faecalis could be transferred by horizontal gene transfer to S. aureus, conferring high-level vancomycin resistance to S. aureus.[4] Until 2002 such a genetic transfer was not reported for wild S. aureus strains.
In 2002, a VRSA strain was isolated from the catheter tip of a diabetic, renal dialysis patient in Michigan.[5] The isolate contained the mecA gene for methicillin resistance. Vancomycin MICs of the VRSA isolate were consistent with the VanA phenotype of Enterococcus species, and the presence of the vanA gene was confirmed by polymerase chain reaction. The DNA sequence of the VRSA vanA gene was identical to that of a vancomycin-resistant strain of Enterococcus faecalis recovered from the same catheter tip. The vanA gene was later found to be encoded within a transposon located on a plasmid carried by the VRSA isolate.[6] This transposon, Tn1546, confers vanA-type vancomycin resistance in enterococci.[7]
Since 2002, ten additional VRSA isolates have been reported, eight from the United States, one from Iran, and one from India.[2]
Trimethoprim/sulfamethoxazole was shown to have efficacy in treating the first known US case of VRSA. Linezolid, quinupristin/dalfopristin and daptomycin are treatments of consideration.