Abstract
BackgroundThe development of hVISA has been associated with vancomycin clinical failures and is commonly misidentified in clinical microbiology laboratories. Therefore, the objectives of this present study was to improve the reliability of methodologies and criteria for identifying hVISA, evaluate the prevalence of hVISA among clinical bloodstream isolates of S. aureus and determine if there exists a relationship between accessory gene regulator (agr) dysfunction and the hVISA phenotype.MethodsThe presence of hVISA in 220 clinical S. aureus isolates (121 MSSA, 99 MRSA) from bloodstream infections was examined by CLSI broth microdilution, Macro & Standard Etest. Isolates which were classified as hVISA by Macro Etest, were additionally evaluated using a modified PAP-AUC method using a modified starting inoculum of 1010 CFU/mL, and growth on brain heart infusion agar with 4 mg/L vancomycin (BHIV4) at 108 and 1010 CFU/mL, and agr function was assessed by delta-hemolysin production.ResultsBroth microdilution MIC50/90 of S.aureus and hVISA was 1.0/2.0 and 1.5/2.0 mg/L (p= 0.02), respectively. Macro Etest identified 12 (5.5%) hVISA isolates; higher among MRSA (9.1%) versus MSSA (2.5%) (p = 0.03). The mean modified PAP-AUC ratios (> 0.8) of 7 MRSA strains and 3 MSSA strains were significantly different (p = 0.001). 58% of hVISA strains were found to be agr dysfunctional when 21% of MRSA strains were agr dysfunctional. hVISA was detected among S. aureus bloodstream isolates, which were classified as susceptible among clinical microbiology laboratories.ConclusionsEvaluating the correlation between Etest MICs and modified PAP-AUC ratio values will add further improvement of discriminating hVISA, and agr dysfunction may be predictive of strains which display a greater predilection to display the hVISA phenotype.
Highlights
The development of Heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) has been associated with vancomycin clinical failures and is commonly misidentified in clinical microbiology laboratories
HVISA was first characterized in 1997 [6]. hVISA is defined as isolates which are classified by the Clinical and Laboratory Standard Institute (CLSI) as having a vancomycin broth microdilution minimum inhibitory concentration (MIC) in the susceptible range where a notable subpopulation of cells with MICs over the susceptibility breakpoint [6]
The proportion of methicillin susceptible S. aureus (MSSA) and MRSA isolates in tested S. aureus isolates were 55 and 45%, respectively (Table 1)
Summary
The development of hVISA has been associated with vancomycin clinical failures and is commonly misidentified in clinical microbiology laboratories. PAP-AUC is labor intensive, it has long been considered the gold standard for hVISA detection [2]. As it relates to genetic factors which can be markers for hVISA, no single resistance gene has been correlated with hVISA development [11,12]; it has been demonstrated that the expression of hVISA phenotype is well associated with dysfunction in the quorum sensing cluster of genes, the accessory gene regulator group (agr), controlling colonization and virulence, as well as a number of other regulators [13]
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