VISA, hetero-VISA and VRSA: the end of the vancomycin era?

282 Staphylococcus aureus is a ubiquitous organism in the human population – 30% to 40% of adults are asymptomatic carriers (1). As a species, staphylococci are among the most hardy of bacteria. They survive many adverse environmental conditions including heat, desiccation and relative cold, and they tolerate high salt concentrations (2). It is therefore not surprising that S aureus has remained a major pathogen in humans, colonizing and infecting both hospitalized patients with reduced immune defences and healthy individuals with intact immune defences, but who have breaches to the normal skin and mucous membrane barriers. S aureus also illustrates the dynamic interaction between pathogenic microorganisms and antimicrobials. The isolation of S aureus strains that are resistant to penicillin G was reported shortly after penicillin became widely available (3). Initially a sporadic occurrence, this type of resistance, which is plasmid borne, spread rapidly through the 1950s and 1960s. By the 1970s, almost all hospital strains and a large number of community strains of S aureus were resistant to penicillin. The development of the semisynthetic penicillinase-resistant agents, methicillin and the isoxazolyl penicillins in 1960 was followed by the report of methicillin-resistant S aureus (MRSA) in 1961 (4). There are several mechanisms of methicillin resistance in staphylococci, including inactivation by beta-lactamase enzymes, penicillin-binding proteins with reduced penicillin binding capacity, and the acquisition of the mecA gene, which encodes new penicillin-binding proteins with low affinity for beta-lactams. The latter mechanism accounts for the majority of resistance to methicillin and other beta-lactams (5). The prevalence of MRSA in hospitalized patients was less than 5% in the early 1970s in most hospital settings worldwide, but within a decade, the prevalence had increased to as high as 40% in many hospitals in the United States and Europe (6,7). In the past 10 to 15 years, MRSA has become increasingly recognized as a major cause of hospital-acquired infections (8). Although MRSA is not more virulent than methicillin-sensitive Staphylococcus aureus, there is some evidence that infections such as pneumonia, endocarditis and cellulitis with MRSA create management difficulties due to delays in recognizing the presence of a resistant strain and cross-resistance to a number of commonly used antibiotics (5). These include most betalactams such as penicillins, cephalosporins and carbapenems, as well as many non-beta-lactam agents. The major risk factors for MRSA colonization include prolonged hospitalization, admission to an intensive care or burn unit, previous antimicrobial drug use and contact with a known MRSA carrier. Vancomycin is the treatment of choice for serious MRSA infections. With the increasing prevalence of MRSA worldwide and the consequent increased use of vancomycin, it was inevitable that infections with vancomycin-resistant S aureus (VRSA) would be reported. The first clinical isolate of S aureus with reduced susceptibility to vancomycin was reported from Japan in 1996 (9). The strain, known as Mu50, had a minimum inhibitory concentration (MIC) to vancomycin of 8 mg/L, which is in the intermediate range based on interpretive criteria according to the National Committee for Clinical Laboratory Standards (NCCLS) (10). Following reports of the emergence of vancomycinintermediate S aureus (VISA), another type of vancomycin resistance in S aureus was reported from Japan in 1997 (11) and was termed hetero-VISA. These strains are susceptible to vancomycin (MIC <4 mg/L), but contain subpopulations of organisms that are capable of growing at a vancomycin concentration of >4 mg/L and have an MIC of ≥8 mg/L. In July 2002, the first documented report of clinical infection VISA, hetero-VISA and VRSA: The end of the vancomycin era?