Systematic Review and Meta-Analysis of the Epidemiology of Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates

BACKGROUND Vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are associated with vancomycin treatment failure, and are becoming an increasing public health problem. Therefore, we undertook this study of 91 published studies and made subgroup comparisons of hVISA/VISA incidence in different study years, locations, and types of clinical samples. We also analyzed the genetic backgrounds of these strains. METHODS A systematic literature review of relevant articles published in PubMed and EMBASE from January 1997 to August 2014 was conducted. We selected and assessed journal articles reporting the prevalence rates of hVISA/VISA. RESULTS The pooled prevalence of hVISA was 6.05% in 99,042 methicillin-resistant S. aureus (MRSA) strains and that of VISA was 3.01% in 68,792 MRSA strains. The prevalence of hVISA was 4.68% before 2006, 5.38% in 2006-2009, and 7.01% in 2010-2014. VISA prevalence was 2.05%, 2.63%, and 7.93%, respectively. In a subgroup analysis of different isolation locations, the prevalence of hVISA strains was 6.81% in Asia and 5.60% in Europe/America, and that of VISA was 3.42% and 2.75%, respectively. The frequencies of hVISA isolated from blood culture samples and from all clinical samples were 9.81% and 4.68%, respectively, and those of VISA were 2.00% and 3.07%, respectively. The most prevalent genotype was staphylococcal cassette chromosome mec (SCCmec) II, which accounted for 48.16% and 37.74% of hVISA and VISA, respectively. Sequence Type (ST) 239 was most prevalent. CONCLUSION The prevalence of hVISA/VISA has been increasing in recent years, but has been grossly underestimated. Its incidence is higher in Asia than in Europe/America. hVISA is isolated from blood culture samples more often than from other samples. These strains are highly prevalent in epidemic MRSA strains. This study clarifies the epidemiology of hVISA/VISA and indicates that the detection of these strains and the control of nosocomial infections must be strengthened.