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

RESEARCH ARTICLE Systematic Review and Meta-Analysis of the Epidemiology of Vancomycin-Intermediate and Heterogeneous VancomycinIntermediate Staphylococcus aureus Isolates Shanshan Zhang1, Xiaoxi Sun2, Wenjiao Chang2, Yuanyuan Dai2, Xiaoling Ma2* 1 School of Medicine, Shandong University, Ji’nan, 250061, PR China, 2 Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, 230001, PR China * a11111 Abstract Background OPEN ACCESS Citation: Zhang S, Sun X, Chang W, Dai Y, Ma X (2015) Systematic Review and Meta-Analysis of the Epidemiology of Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates. PLoS ONE 10(8): e0136082. doi:10.1371/journal.pone.0136082 Editor: Herminia de Lencastre, Rockefeller University, UNITED STATES Received: March 27, 2015 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. Accepted: July 29, 2015 Published: August 19, 2015 Results Copyright: © 2015 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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. Data Availability Statement: All relevant data are within the paper. Funding: The authors have no support or funding to report. Competing Interests: The authors have declared that no competing interests exist. PLOS ONE | DOI:10.1371/journal.pone.0136082 August 19, 2015 1 / 22 Systematic Review and Meta-Analysis of Epidemiology of VISA/hVISA 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. Introduction Staphylococcus aureus, one of the major nosocomial and community-acquired pathogens, causes a variety of clinical problems, including infections of the skin and soft tissues [1]. Since the 1960s, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has increased at a dramatic rate [2, 3], and is associated with higher rates of morbidity and mortality than methicillin-susceptible S. aureus (MSSA) [4]. Glycopeptides, such as vancomycin, are popular and effective antimicrobial drugs for treating MRSA. Unfortunately, vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) have been reported since 1997. hVISA is an S. aureus isolate with a minimum inhibitory concentration (MIC) for vancomycin within the susceptible range when tested with routine methods, but in which a proportion of the cell population is within the vancomycinintermediate range [5]. hVISA/VISA infections are commonly associated with persistent infections, prolonged bacteremia, and/or prolonged hospitalization [6–9]. Today, there is growing concern that hVISA and VISA are becoming prevalent worldwide [10–12]. In recent years, there have been many reports from single medical centers or individual countries of the incidence of hVISA/VISA, but few systematic reviews or meta-analyses on their prevalence. The review by Liu et al. on the epidemiology of hVISA/VISA was published over 10 years ago [13]. Another meta-analysis, by Van Hal et al., selectively analyzed the clinical significance and outcomes of hVISA [9]. In this systematic review and meta-analysis, we pooled the published studies that have reported the prevalence of hVISA/VISA, and made subgroup comparisons of the incidence of hVISA/VISA in different years, locations, and types of clinical samples. We also analyzed the genetic backgrounds of these strains. The results of this study will help to clarify the epidemiology of hVISA/VISA and will advance the control and management of these drug-resistant isolates. Methods Search strategy Two independent examiners (S.S.Z. and X.X.S.) performed a systematic literature review of potentially relevant studies pertaining to VISA and hVISA. The studies were identified in the PubMed and EMBASE databases from articles published between January 1997 and August 2014. The following terms and connectors were used in the search strategy: (1) ‘vancomycinintermediate Staphylococcus aureus’, VISA; (2) ‘heterogeneous vancomycin-intermediate Staphylococcus aureus’, hVISA; (3) ‘Staphylococcus aureus with reduced vancomycin susceptibility’, SA-RVS; (4) ‘glycopeptide-intermediate Staphylococcus aureus’, GISA; and (5) ‘heterogeneous glycopeptide-intermediate Staphylococcus aureus’, hGISA. The search was restricted to human studies. PLOS ONE | DOI:10.1371/journal.pone.0136082 August 19, 2015 2 / 22 Systematic Review and Meta-Analysis of Epidemiology of VISA/hVISA Selection of studies Studies identified in the literature search were checked by title and abstract. The papers with relevant abstracts were examined in full. The criteria for the inclusion and exclusion of the studies were established by the investigators before the literature was reviewed. The inclusion criteria were as follows: (1) studies that were original articles, short communications, correspondence, or letters that provided sufficient original data about the prevalence of hVISA/ VISA; (2) studies in which all MRSA strains were randomly selected; (3) stud (...truncated)