The global scope of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA): a meta-analysis of its clinical impact, molecular epidemiology, and diagnostic challenges across 15,165 isolates

OBJECTIVES: To systematically evaluate the clinical impact of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA), characterize its global molecular epidemiology, and compare the accuracy of mainstream diagnostic screening methods. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Embase, and Web of Science for relevant literature published up to February 28, 2025. We conducted meta-analyses to calculate pooled odds ratios (ORs) for clinical outcomes, pooled prevalence for staphylococcal cassette chromosome mec (SCCmec) types, and synthesized the diagnostic accuracy of phenotypic screening methods using a bivariate random-effects model. RESULTS: A total of 59 studies were included, with a pooled hVISA prevalence of 12.0%. In clinical outcome analyses, hVISA infection was associated with higher odds of vancomycin treatment failure (OR = 2.68, 95% CI: 1.74-4.14) and a modest increase in all-cause mortality (OR = 1.35, 95% CI: 1.03-1.77). For persistent or recurrent bacteremia, the pooled estimate did not reach statistical significance (OR = 1.82, 95% CI: 0.62-5.34), and substantial heterogeneity was observed across studies. Molecular epidemiology analysis showed that SCCmec types II (26%) and III (22%) were predominant globally, with marked geographic variation. In diagnostic performance analysis, agar screening methods demonstrated higher pooled sensitivity (0.81) compared with Etest-based methods (0.73), whereas specificity was slightly lower (0.93 vs. 0.96). Overall diagnostic accuracy was comparable between methods, with overlapping summary AUC values (~ 0.92). CONCLUSION: hVISA represents a clinically relevant phenotype associated with an increased likelihood of vancomycin treatment failure and a modest elevation in mortality risk. The association with persistent bacteremia remains uncertain due to limited data and heterogeneity. Geographic variation in molecular distribution was observed. Although agar screening methods demonstrated higher sensitivity for detection, substantial between-study heterogeneity warrants cautious interpretation of pooled diagnostic estimates.