Emergence of Methicillin-Resistant Staphylococcus aureus with Intermediate Glycopeptide Resistance

Abstract

Methicillin-resistant Staphylococcus aureus is a pathogen that is associated with serious infections that pose a significant risk of morbidity and mortality because of their multidrug resistant nature. Until recently, therapeutic options were limited to vancomycin, making the use of this drug widespread. Unfortunately, the continued application of this drug has led to the emergence of glycopeptide intermediate susceptible S. aureus (GISA). By definition, these organisms demonstrated a vancomycin minimum inhibitory concentration (MIC) of >4 mg/L and <32 mg/L. However, although the mechanism of resistance is not fully elucidated at this time, GISA strains have demonstrated thickened or aggregated cell walls, an increase in penicillin binding proteins and greater autolytic activity. At present, the overall number of reported cases of GISA is relatively low. In most cases, thus far, prolonged courses of vancomycin were reported. A few cases reported monitoring serum vancomycin concentrations but because of limited information, no association with outcome can be made. Whether these GISA strains will become more widespread or evolve into fully glycopeptide resistant strains is unknown at this time. Although there are a number of new agents that possess activity against these pathogens, there is no consensus regarding specific recommendations for treatment. Strict infection control practices, routine screening for resistance and controlled use of antibacterial agents, especially vancomycin, are critical steps in preventing the further development of resistance among staphylococci.

Characterization of Vancomycin-Heteroresistant Staphylococcus aureus from the Metropolitan Area of Detroit, Michigan, over a 22-Year Period (1986 to 2007)

“…Vancomycin is the primary treatment for this pathogen; however, the increasing use of this agent for a variety of gram-positive organisms, including MRSA, contributes to the growing burden of nonsusceptible strains in both the community and hospital settings (17). Unfortunately, vancomycin-intermediate S. aureus (VISA) and heteroresistant VISA (hVISA) strains have now been reported and are associated with vancomycin treatment failures (7,10,27). Although the presence of VISA is routinely screened for on the basis of the vancomycin MIC exceeding the breakpoint for susceptibility (27, 33), screening for hVISA is not routinely performed (15,33,37).…”

Comparison of Detection Methods for Heteroresistant Vancomycin-Intermediate Staphylococcus aureus , with the Population Analysis Profile Method as the Reference Method

“…Such strains are susceptible in vitro to vancomycin (MIC Ͻ 4 g/ml) and thus are classified as susceptible by standard clinical laboratory methods but contain subpopulations of 1 in 10 6 cells that can grow in the presence of Ն4 g/ml of vancomycin (9,27). Although the true prevalence of hVISA is unknown, estimates from a limited number of studies range from 1.3% to 27% of all MRSA isolates (1,4,5,8,21).…”

Vancomycin Susceptibility Trends and Prevalence of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus in Clinical Methicillin-Resistant S. aureus Isolates

“…With these characteristics, hVISA is considered the precursor of vancomycin-intermediate S. aureus (51). Infections caused by hVISA are a growing concern in hospitals, resulting in prolonged bacteremia, endocarditis, and osteomyelitis and ultimately leading to vancomycin treatment failure (4,9,16,37). Contributing to this problem of hVISA is the fact that current diagnostic methods often fail to detect this resistance phenotype, and additional screening is required to detect hVISA (15,24).…”