Relationship between Vancomycin-Resistant Staphylococcus aureus, Vancomycin-Intermediate S. aureus, High Vancomycin MIC, and Outcome in Serious S. aureus Infections

Abstract

e Vancomycin has been used successfully for over 50 years for the treatment of Staphylococcus aureus infections, particularly those involving methicillin-resistant S. aureus. It has proven remarkably reliable, but its efficacy is now being questioned with the emergence of strains of S. aureus that display heteroresistance, intermediate resistance, and, occasionally, complete vancomycin resistance. More recently, an association has been established between poor outcome and infections with strains of S. aureus with an elevated vancomycin MIC within the susceptible range. This minireview summarizes the definitions, mechanisms, clinical impact, and laboratory identification of reduced vancomycin susceptibility in S. aureus and discusses practical issues for the diagnostic laboratory in testing and interpreting vancomycin susceptibility for S. aureus infections. HISTORY AND DEFINITION OF REDUCED VANCOMYCIN SUSCEPTIBILITY IN STAPHYLOCOCCUS AUREUS

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

“…Accumulating evidence of increasing resistance, unachievable pharmacokinetic/pharmacodynamic (PK/PD) targets and poorer outcomes challenges the suitability of the prime place of vancomycin in treatment regimens and guidelines [1][2][3][4][5][6].…”

Asymptomatic colonization of Staphylococcus aureus with intermediate resistance to vancomycin harboring vanB resistance gene

“…Nevertheless, some data in the literature raise the possibility that factors in the invading bacterium may also contribute. Examination of the vancomycin minimal inhibitory concentration (MIC) value of MRSA strains that were recovered from patients with failed therapy showed that therapeutic failure correlated significantly with the vancomycin MIC value of the strains, even when this antibiotic was not used for therapy [11]. These data suggest that the vancomycin susceptibility profile of MRSA strains correlates with some aspects of the invasive potential of the bacteria.…”

Identification of a distinctive phenotype for endocarditis-associated clonal complex 22 MRSA isolates with reduced vancomycin susceptibility

“…Firstly, these high-V MIC isolates are likely to have undergone other molecular changes, so a more comprehensive genotypic and phenotypic analysis of these isolates will now be required to extend these findings [8,9]. Specifically, we did not use an established in vitro or in vivo endocarditis model, or a measure of growth rate, which we plan to do in future studies.…”

“…VISA and hVISA isolates have multiple phenotypic and metabolic differences compared with susceptible isolates, such as reduced autolysis and gradual thickening of the cell wall, changes in global gene regulators including down-regulation of agr, increased expression of surface adhesins that bind fibrinogen and fibronectin, and attenuated virulence [3,[8][9][10][11][12][13]. There is also clinical evidence that VISA and hVISA isolates are less virulent, with lower acute mortality and less shock reported in some studies [14,15].…”

“…It may be that the fitness cost of reduced susceptibility to vancomycin is reduced acute virulence, but this allows bacteria to survive in the body for longer and increases the chance of distal focus infections. Given that vancomycin is the mainstay of therapy for MRSA BSIs [8,9], the association of VISA and hVISA with endocarditis may also result from prolonged bacteraemia on vancomycin therapy, particularly in the setting of low serum vancomycin levels.…”