Vancomycin-resistant Staphylococcus aureus

Vancomycin-resistant "Staphylococcus aureus" (VRSA) is a strain of "Staphylococcus aureus" that has become resistant to the glycopeptide antibiotic vancomycin. With the increase of staphylococcal resistance to methicillin, vancomycin (or teicoplanin) is often a treatment of choice in infections with methicillin-resistant "Staphylococcus aureus" (MRSA).

Vancomycin resistance is still a rare occurrence. Unfortunately, VRSA may also be resistant to meropenem and imipenem, two other antibiotics that can be used in sensitive staphylococcus strains.

VISA (vancomycin-intermediate "Staphylococcus aureus") was first identified in Japan in 1996 and has since been found in hospitals in England, 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 deplete the vancomycin available to kill the bacteria. This worries many physicians and microbiologists because it leads to high level resistance to vancomycin in "Staphylococcus aureus". This has the potential of spreading rapidly throughout large populations of "Staphylococcus aureus" in hospitals, as opposed to the traditional VISA mode of intermediate resistance to vancomycin, which has to be acquired by the bacterium during treatment with this drug.

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.

Clinical experience suggested that development of resistance to vancomycin by "S aureus" was difficult, despite occasional reports of resistance at a low-level. An "in vitro" demonstration in 1992 showed that the resistance genes from enterococci could be passed to "S aureus" and subsequently expressed, thus conferring vancomycin resistance. This was a matter of concern, but until 2002 such a transfer had not been reported in wild strains.

In 2002, a newly reported VRSA was isolated from the catheter tip of a renal dialysis patient in Michigan. The isolate contained both the mecA gene for methicillin resistance and the vanA gene for vancomycin resistance. MICs were consistent with the vanA phenotype of enterococcus. The presence of the vanA gene was confirmed by polymerase chain reaction and was located on a 60-kb plasmid. 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 culture. The isolate was, however, susceptible to trimethoprim/sulfamethoxazole, minocycline, linezolid, and quinupristin/dalfopristin. This VRSA was, thus, the first likely transfer "in vivo" of high-level vancomycin resistance from "E faecalis" to "S aureus". Should this plasmid, or another one like it, be transferred from one "S aureus" strain to another as rapidly as was the plasmid containing the beta-lactamase gene, this may herald the demise of vancomycin as a clinically useful agent.

The importance of the newly characterized efflux mechanism is not that it confers resistance against any particular antimicrobial agent. In fact, this efflux pump resistance mechanism was not very impressive in the type of resistance it conferred. However, this is the second of an estimated 12-15 efflux pump resistance mechanisms that "S aureus" strains are thought to have. One of these efflux mechanisms in the future could mutate so that it conferred resistance to drugs such as minocycline, linezolid, and quinupristin/dalfopristin. Once again, "S aureus" has demonstrated its propensity to become resistant despite attempts to develop new anti-staphylococcal agents.

Notes

* Chang S, Sievert DM, Hageman JC, Boulton ML, Tenover FC, Downes FP, Shah S, Rudrik JT, Pupp GR, Brown WJ, Cardo D, Fridkin SK. "Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene." N Engl J Med 2003;348:1342-7. PMID 12672861.

ee also

* Drug resistance
* Extensively drug-resistant tuberculosis (XDR-TB)
* Methicillin-resistant Staphylococcus aureus (MRSA)
* Vancomycin-resistant enterococcus (VRE)