Vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus

Vancomycin minimal inhibitory concentration (MIC) interpretive criteria for Staphylococcus aureus (S. aureus) have been recently revised. Increasing reports of vancomycin treatment failure in infections due to strains with elevated MICs (2 mcg/mL) were the basis for this revision.

Testing should incorporate the following CLSI recommendations: 
Inoculum: Use direct colony suspension using a 0.5 McFarland standard to prepare inoculum.
Incubation: 35°C, ambient air, for full 24 hr.

Revised breakpoints

Mechanism of resistance

Recommended  test

Vancomycin susceptible ≤2 mcg/ml

Vancomycin intermediate (VISA) 4 to 8 mcg/ml Synthesis of an unusually thickened cell wall containing dipeptides (D-Ala-D-Ala) MIC
Vancomycin resistant (VRSA) ≥16 mcg/ml Acquisition of vanA gene MIC

Hetero-resistance VISA: Hetero-resistant vancomycin-intermediate S. aureus (hVISA) refers to VISA strains in which subpopulations display variable rather than uniform susceptibility to vancomycin. Heteroresistant strains of S. aureus contain subpopulations of bacteria with vancomycin MICs in the intermediate range, but the vancomycin MIC for the entire population of the strain remains within the susceptible range

Most automated methods can detect VRSA but they are not optimized well for VISA detection. VISA isolates could not be detected by disk diffusion. Methods that typically detect VISA are non-automated MIC methods including reference broth micro-dilution, agar dilution, and E-test using a 0.5 McFarland standard to prepare inoculum.
According to the newest CLSI (formerly NCCLS) standards, a vancomycin-intermediate or resistant result should be verified by repeating a validated MIC method and the organism identification.

The most accurate method for detecting heteroresistant subpopulations is with performance of population analysis profiles.

Additional susceptibility testing is warranted in patients with repeated isolates of S. aureus from normally sterile sites despite seemingly appropriate therapy for longer than 7 day.

Infection control:
There is significant concern about the spread of VISA and VRSA among patients because of limited treatment optionsSo they should be reported to the infection control team.


  • Cui, L, Ma, X, Sato, K, et al. Cell wall thickening is a common feature of vancomycin resistance in Staphylococcus aureus. J Clin Microbiol 2003; 41:5.

  • Tenover, FC, Moellering RC, Jr. The rationale for revising the Clinical and Laboratory Standards Institute vancomycin minimal inhibitory concentration interpretive criteria for Staphylococcus aureus. Clin Infect Dis 2007; 44:1208.

  • Satola SW.Comparison of Detection Methods for Heteroresistant Vancomycin-Intermediate Staphylococcus aureus,with the Population Analysis Profile Method. J Clin Microbiol 2011;177-183.