CHICAGO — There is no indication to test routinely for hetero-resistant vancomycin-intermediate Staphylococcus aureus (hVISA), Dr. Benjamin Howden said at the annual Interscience conference on Antimicrobial Agents and Chemotherapy.
S. aureus strains with reduced vancomycin susceptibility are an emerging and clinically important problem, because vancomycin is the primary antimicrobial agent used for treating methicillin-resistant S. aureus (MRSA) infections. S. aureus strains with vancomycin minimally inhibitory concentrations (MICs) of 2 or less, 4–8, or greater than 8 mcg/mL are defined as susceptible, intermediately resistant, or resistant, respectively, according to the Clinical and Laboratory Standards Institute.
Before January 2006, the susceptibility breakpoints were 4 or less, 8–16, or greater than 16 mcg/mL, but were revised to reflect a growing body of data indicating that S. aureus isolates with MICs of 4 mcg/mL are strongly associated with vancomycin treatment failure. Heterogeneous VISA strains fall into the susceptible category.
It's difficult to determine how common hVISA is because different groups use different criteria to define and detect hVISA, said Dr. Howden of the infectious diseases department, Austin Health, Melbourne. Unpublished data from his group, however, show that 65% of 1,500 isolates with an MIC of 2 mcg/mL were positive for hVISA. Also, several groups, including one from North Carolina (J. Antimicrob. Chemother. 2007;60:788–94), report an increasing proportion of vancomycin-susceptible MRSA blood isolates with a vancomycin MIC of 1 mcg/mL. This “MIC creep … means you will be seeing more hVISA over time,” he said.
Population analysis profiling (PAP) is considered the accepted standard test for detecting hVISA, but it is labor intensive and costly. Several other methods have been developed recently, with the Etest macromethod showing good sensitivity and specificity, compared with PAP, Dr. Howden said.
Another issue to be aware of when testing for hVISA is that it can emerge during failed vancomycin therapy. Dr. Howden recalled one patient who developed hVISA over 3 weeks of failed vancomycin therapy, which he defines as an S. aureus-positive blood culture after at least 7 days of vancomycin therapy or a sterile-site isolate positive for S. aureus after at least 21 days of vancomycin therapy. “It's not enough to test an initial clinical isolate, but later isolates as well,” he said.
A clear association exists between vancomycin treatment failure and the subsequent development of hVISA, but it's unclear if hVISA is associated with subsequent treatment failure. Clinical factors that can put patients at increased risk for vancomycin treatment failure include high bacterial load, persistent bacteremia, large undrained abscesses, bacterial endocarditis, and infected prosthetic devices.
Vancomycin failure has also been attributed to factors within the hVISA strain itself, including changes in the thickness and composition of the S. aureus cell wall; reduced susceptibility to vancomycin; and reduced RNAIII expression, autolytic activity, and biofilm formation. As to whether clinical vs. “bug” factors are more important, Dr. Howden said, “We believe it is probably a combination of both, and is what we consider the perfect clinical storm.”
Although much effort was spent in the past on screening all S. aureus isolates for hVISA, a more practical approach to MRSA and hVISA/VISA is to be wary of patients with high bacterial loads and high-risk disease such as deep abscess, prosthetic device infection, and endocarditis; to aim for high vancomycin serum levels (15–20 mcg/mL) in patients without proven, serious MRSA infection; and to debulk abscesses whenever possible. Finally, clinicians should be aware of the possibility of reduced susceptibility to other agents such as daptomycin and possibly tigecycline, said Dr. Howden, who declared no financial conflicts of interest.