Skip to main content
NCBI home page
PLOS One logoLink to PLOS One
. 2015 Aug 19;10(8):e0136082. doi: 10.1371/journal.pone.0136082

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

Shanshan Zhang 1, Xiaoxi Sun 2, Wenjiao Chang 2, Yuanyuan Dai 2, Xiaoling Ma 2,*
Editor: Herminia de Lencastre3
PMCID: PMC4546009  PMID: 26287490

Abstract

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.

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 vancomycin-intermediate 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) ‘vancomycin-intermediate 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.

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) studies that used normative and publicly accepted detection methods for hVISA/VISA; and (4) studies that were published in English. The exclusion criteria were: (1) studies that contained duplicate data or were overlapping articles; (2) reviews and conference abstracts; and (3) articles that included fewer than 10 cases.

Data extraction

Two authors independently ascertained the characteristics of each study, including the first author’s surname, year of publication, continent, country, study years, isolate source, detection method, hVISA frequency, VISA frequency, and genotypes. When there was disagreement, the relevant paper was reviewed and the differences were resolved by consensus.

Assessment of study quality

The studies were assessed for quality, and only high-quality studies were included in the analysis. The criteria for high-quality studies were (1) that they provided basic data that included the study period and area, total number of isolates tested, and number of hVISA/VISA isolated; and (2) that they used dilution methods or E-test to detect VISA, and population analysis profile–area under the curve (PAP-AUC), macromethod Etest (MET), or screening agar to detect hVISA. When two studies overlapped, the more recent and larger study was included in the analysis. If one article included more than one study period, it was divided into several independent studies.

Statistical analysis

Statistical analyses were performed with STATA version 12.0. The data were pooled using the fixed-effects model (FEM) [14] and the random-effects model (REM) [15]. Statistical heterogeneity was assessed using the Cochran Q and I2 statistical methods [16]. P < 0.1 was considered statistically significant. For all analyses, the results of FEM are presented only when there was no heterogeneity between the studies. Otherwise, the results of REM are presented. Freeman–Tukey arcsine transformations were performed to stabilize the variances, and after the meta-analysis, we transformed the summary estimates and the confidence interval (CI) boundaries back to proportions using the sine function [17].

Results

Results of the systematic literature search

In total, 1258 citations were identified in the initial electronic database search. Ultimately, 91 studies were included, based on the inclusion and exclusion criteria (Fig 1). These 91 studies that reported the prevalence of hVISA/VISA included 39 from Asia, 28 from Europe, 21 from America, and 3 from Australia (Table 1) [18–108]. In the pooled analysis, hVISA was reported in 76 studies, with an overall prevalence of 6.05% among 99,042 MRSA strains (95% CI 4.78–7.48), and VISA was reported in 38 studies, with a prevalence of 3.01% among 68,792 MRSA strains (95% CI 1.62–4.83) (Table 2).

Fig 1. Flowchart of study selection.

Fig 1

Open in a new tab

Table 1. Characteristics of the eligible studies.

Study, Year Published Country, Continent Study Year Isolate Source Detection Method a hVISA Frequency (%) and Genotype (%) VISA Frequency (%) and Genotype (%)
Hanaki et al, 2007[76] Japan, Asia 1978–2005 All clinical samples E-test 5/2446
(0.2)5/5 (100) SCCmec II
Hiramatsu et al, 1997[36] Japan, Asia 1996/01–1997/03 All clinical samples BHI 34/1149 (3.0)
Song et al, 2004[38] Asia 1997/01–2000/03 All clinical samples BHI 58/1357 (4.3)
PAP
Wong et al, 1999[20] Hong Kong, Asia 1997/07–1998/06 All clinical samples E-test 3/52 (5.8)
Ike et al, 2001[75] Japan, Asia 1997/09–1997/12 All clinical samples BHI 0/6625 (0)
PAP
Trakulsomboon et al, 2001[45] Thailand, Asia 1998–1999 All clinical samples BHI 5/155 (3.2)
PAP
Neoh et al, 2007[56] Japan, Asia 1998/01–2005/10 Blood samples PAP-AUC 2/20 (10.0)
Kim et al, 2002[27] Korea, Asia 1998/12–1999/08 All clinical samples BHI 24/3363 (0.7) 0/3363 (0)
PAP
Aminaka et al, 2009[34] Japan, Asia 1999 All clinical samples BHI 7/138 (5.1) 0/138 (0)
PAP
Kim et al, 2000[108] Korea,Asia 1999/01–1999/08 All clinical samples PAP 59/3371 (1.8)
Kim et al, 2003[73] Korea, Asia 1999/06–2001/01 All clinical samples BHI 0/439 (0)
PAP
Hsueh et al, 2010[26] Taiwan, Asia 2001/09–2002/08 All clinical samples MIC based 43/1500
(2.9) 43/43 (100) SCCmec III
Wang et al, 2009[70] Taiwan, Asia 2001–2003 All clinical samples BHI 2/13 (15.3) 8/13 (61.5)
PAP 1/2 (50.0) SCCmec IV-ST59 5/8 (62.5) SCCmec IV-ST59
1/2 (50.0) SCCmec III-ST239 3/8 (37.5) SCCmec III-ST239
Ghung et al, 2010[74] Korea, Asia 2001–2006 All clinical samples MIC based 18/41639 (0.04) 15/41639 (0.04)
PAP-AUC 12/18 (66.7) SCCmec II-ST5 12/15(80.0) SCCmec III-ST239
4/18 (22.2) SCCmec IV-ST72 2/15 (13.3) SCCmec II-ST5
1/18 (5.6) SCCmec III-ST239 1/15 (6.7) SCCmec IV-ST72
1/18 (5.6) SCCmec IV-ST1
Lulitanond et al, 2009[46] Thailand, Asia 2002/08–2003/04 All clinical samples BHI 4/533 (0.8)
PAP 4/4 (100) SCCmec III-ST239
Maor et al, 2009[25] Israel, Asia 2003–2006 Blood samples MET 27/223 (12.1)
Maor et al, 2007[82] Israel, Asia 2003/01–2004/12 Blood samples MET 16/264 (6.0)
Ho et al, 2010[81] Taiwan, Asia 2003/03–2003/08 All clinical samples BHI 7/1000 (0.7) 2/1000 (0.2)
PAP-AUC
Aminaka et al, 2009[34] Japan, Asia 2005–2006 All clinical samples BHI 3/477 (0.6) 0/477 (0)
PAP
Sun et al, 2009[83] China, Asia 2005–2007 Blood samples MET 26/200 (13.1) 1/200 (0.5)
PAP-AUC 20/26(77.0) SCCmec III-ST239 1/1 (100) SCCmec II-ST5
5/26 (19.2) SCCmec II-ST5
1/26 (3.8) SCCmec IV-ST59
Campanile et al, 2010[52] India, Asia 2005–2007 All clinical samples BHI, MET 36/139 (25.9) 0/139 (0)
PAP-AUC 3/36 (8.3) ST8
3/36 (8.3) ST239
15/36 (41.7) ST247
12/36 (33.3) ST228
3/36 (8.3) others
Chen et al, 2011[58] China, Asia 2005–2008 All clinical samples PAP-AUC 62/559 (11.1) 0/559 (0)
Fong et al, 2009[23] Singapore, Asia 2005/01–2006/12 Blood samples MET 3/56 (5.4)
Wang et al, 2013[55] Taiwan, Asia 2005/01–2009/12 Blood samples E-test GRD 16/284 (5.6)
PAP-AUC 7/16 (43.8) ST239
5/16 (31.4) ST5
1/16 (6.2) ST59, ST45, ST398, ST900
El Ayoubi et al, 2014[48] Lebanon, Asia 2006/02–2013/03 All clinical samples MIC based 5/113 (3.8)
Lulitanond et al, 2009[46] Thailand, Asia 2006/09–2007/12 All clinical samples BHI 8/361 (2.2) 3/361 (0.8)
PAP 8/8 (100) SCCmec III-ST239 2/3 (66.7) SCCmec III-ST239
1/3 (33.3) SCCmec II-ST5
Wang et al, 2013[84] China, Asia 2007/07-2009/03 All clinical samples MET 25/122 (20.5)
23/25 (92.0) SCCmec III
2/25 (8.0) SCCmec II
Hanaki et al, 2014[19] Japan, Asia 2008/01–2011/05 Blood samples MET 55/830 (6.5) 8/830 (1.0)
PAP-AUC
Park et al, 2012[28] Korea,Asia 2008/08–2010/09 Blood samples E-test 101/268 (37.7)
PAP-AUC 73/268 (72.3) SCCmec II-ST5
17/268(16.8) SCCmec IV-ST72
9/268 (8.9) SCCmec III-ST239
2/268 (3.0) others
Gowrishankar et al, 2013[40] India, Asia 2009–2010 All clinical samples MHA 10/63 (15.9)
Norazah et al, 2012[79] Malaysia, Asia 2009/01–2009/12 All clinical samples E-test GRD 2/43 (4.7)
PAP-AUC
Ramli et al, 2012[94] Malaysia, Asia 2009/02–2009/05 All clinical samples E-test GRD 7/320 (2.2)
PAP-AUC
Lin et al, 2012[72] Taiwan, Asia 2009/03–2009/12 Blood samples MET 5/62 (8.1)
PAP-AUC 3/5 (60.0) SCCmec III-ST239
1/5 (20.0) SCCmec III-ST900
1/5 (20.0) SCCmec II-ST5
Dubey et al, 2013[99] India, Asia 2009/09–2012/04 All clinical samples E-test 545/1214 (44.9)
Khanal et al, 2010[87] Nepal, Asia 2010 All clinical sample Arg screening 80/300 (26.6)
Chaudhari et al, 2015[51] India, Asia 2010/09–2013/03 All clinical samples BHI 4/58 (6.9)
PAP-AUC
Panomket et al, 2014[68] Thailand, Asia 2010/11–2011/11 All clinical samples BHI 2/68 (2.9)
PAP-AUC
Liu et al, 2014[71] China, Asia 2011/06–2012/05 All clinical samples PAP-AUC 17/77 (22.1)
15/17(88.2) SCCmec III-ST239
1/17 (5.9) SCCmec III-ST5
1/17 (5.9) SCCmec II-ST1301
Kaleem et al, 2012[31] Pakistan, Asia 2012 All clinical samples E-test 6/347 (1.7)
Guo et al, 2013[100] China, Asia 2012/06–2012/12 All clinical sample MIC based 1/1790 (0.06)
Chaudhary et al, 2013[85] India, Asia 2013 All clinical samples MHA 8/130 (6.1)
E-test
Wootton et al, 2001[69] UK, Europe 1983–1999 All clinical sample E-test 0/100 (0)
PAP-AUC
Robert et al, 2006[32] France, Europe 1983–2001 All clinical samples E-test 1/1445 (0.07)
Geisel et al, 1999[39] Germany, Europe 1992–1998 All clinical samples BHI 7/85 (8.2)
Kantzanou et al,1999[91] Greece, Europe 1994–1997 All clinical samples E-test 1/72 (1.5)
PAP
Uçkay et al, 2012[54] Switzerland, Europe 1995/01–2003/08 All clinical samples BHI 55/208 (26.4)
Bierbaum et al, 1999[80] Germany, Europe 1997 All clinical samples BHI 2/367 (0.5)
PAP
Bert et al, 2003[88] France, Europe 1997/01–2002/01 All clinical samples MET 13/48 (27.1)
PAP
Schmitz et al, 1999[101] Europe 1997/04–1998/04 All clinical samples E-test 0/302 (0)
Marchese et al, 2000[50] Italy, Europe 1997/08–1998/12 All clinical samples BHI 2/179 (1.1)
PAP
Canton et al, 1999[90] Spain, Europe 1997/10–1998/01 All clinical samples E-test 12/248 (4.8)
Fitzgibbon et al, 2007[60] Ireland, Europe 1998–2004 All clinical samples MET 73/3189 (2.3)
PAP-AUC
Sancak et al, 2005[67] Turkey, Europe 1998/01–2002/01 All clinical samples MET 46/256 (18.0) 0/256 (0)
PAP
Aucken et al, 2000[102] UK, Europe 1998/05–1999/04 All clinical samples MIC 0/11242 (0)
BHI
Reverdy et al, 2001[59] French, Europe 1998/11–1999/04 All clinical samples MET 5/171 (2.9)
PAP
Lassence et al, 2006[30] France, Europe 1999–2000 All clinical samples MHA 11/329 (3.3)
E-test
Denis et al, 2002[41] Belgium, Europe 1999/01–1999/12 Blood samples BHI 4/2145 (0.1) 3/2145 (0.1)
PAP
Vaudaux et al, 2012[86] Switzerland, Europe 2000–2008 All clinical samples MHA 13/57 (31.7)
13/13 (100) SCCmec I-ST228
Nonhoff et al, 2005[65] Belgium, Europe 2001/01–2001/12 All clinical samples E-test 3/455 (0.7)
2/3 (66.7) SCCmec I
1/3 (33.3) SCCmec IV
Cartolano et al, 2004[66] France, Europe 2000/06 All clinical samples MHA 31/1070 (2.9)
PAP-AUC
Garnier et al, 2006[18] France, Europe 2001/07–2002/06 All clinical samples MET 255/2300 (11.1)
PAP-AUC
Nakipoglu et al, 2005[61] Turkey, Europe 2001/09–2002/04 All clinical samples BHI 7/135 (5.1)
PAP
Mlynarczyk et al, 2003[96] Poland, Europe 2002 All clinical samples PAP-AUC 5/103 (4.8) 0/103 (0)
Bataineh et al, 2006[93] Spain, Europe 2002/04–2004/08 All clinical samples MHA 5/139 (3.6)
E-test
Piérard et al, 2004[95] Belgium, Europe 2003 All clinical samples MET 5/1002 (0.5) 1/1002 (0.1)
PAP
Kirby et al, 2010[98] UK, Europe 2004–2006 All clinical samples MET 86/2550 (3.4)
PAP-AUC
Lewis et al, 2009[43] UK, Europe 2005–2007 Blood samples MET 35/195 (18.0)
35/35 (100) SCCmec IV
Parer et al, 2012[78] France, Europe 2007 All clinical samples MHA 12/20 (60.0)
PAP-AUC
Sancak et al, 2013[103] Turkey, Europe 2009–2010 Blood samples MET 24/175 (13.7) 0/175 (0)
PAP-AUC
Rybak et al, 2008[21] USA, America 1986–1993 All clinical samples MET 5/225 (2.2) 1/225 (0.4)
PAP-AUC 3/5 (56.9) SCCmec II
2/5 (38.4) SCCmec IV
Ariza et al, 1999[104] USA, America 1990/01–1997/12 All clinical samples E-test 14/19 (73.7)
PAP
Rybak et al, 2008[21] USA, America 1994–2002 All clinical samples MET 27/356 (7.6) 8/356 (2.3)
PAP-AUC 15/27 (56.9) SCCmec II
10/27 (38.4) SCCmec IV
2/27 (4.7) others
Adam et al, 2010[33] Canada, America 1995–2006 All clinical samples E-test GRD 25/475 (5.3)
PAP-AUC 16/25 (64.0) SCCmec II
6/25 (24.0) SCCmec I
2/25 (8.0) SCCmec III
1/25 (4.0) SCCmec IV
Musta et al, 2009[105] USA, America 1996–1997 Blood samples MHA 8/61 (13.1)
E-test 7/8 (93.0) SCCmec II
1/8 (7.0) SCCmec IV
Hubert et al, 1999[49] USA, America 1997 All clinical samples MHA 4/630 (0.6)
PAP-AUC
Tallent et al, 2002[106] USA, America 1997/01–2000/12 Blood samples MIC based 1/619 (0.2)
PAP
Franchi et al, 1999[97] USA, America 1997/03–1997/05 All clinical samples E-test PAP 0/30 (0)
Fridkin et al, 2003[42] USA, America 1999/03–2000/12 All clinical samples BHI 6/102 (5.8)
Eguia et al, 2005[63] USA, America 1999/12–2000/08 All clinical samples BHI 0/211 (0)
Musta et al, 2009[105] USA, America 2000–2001 Blood samples MHA 5/55 (9.1)
E-test 5/5 (100) SCCmec II
Pitz et al,2011[107] USA, America 2000–2008 Blood samples E-test GRD 2/167 (1.2)
PAP-AUC
Musta et al, 2009[105] USA, America 2002–2003 Blood samples MHA 37/187 (19.8)
E-test 34/37 (93.0) SCCmec II
3/37 (7.0) SCCmec IV
Sader et al, 2009[77] USA, America 2002–2006 Blood samples MET 36/268 (13.4)
PAP-AUC
Pastagia et al, 2009[22] USA, America 2002–2007 Blood samples E-test 45/699 (6.4) 118/699 (16.9)
Khosrovaneh et al, 2004[47] USA, America 2002/01–2002/12 Blood samples BHI 3/22 (13.6)
PAP-AUC
Casapao et al, 2014[44] USA, America 2002/01–2013/06 All clinical samples PAP-AUC 38/266 (18.8)
26/38 (68.4) SCCmec IV
11/38 (28.9) SCCmec II
1/38 (2.7) SCCmec III
Khatib et al, 2011[92] USA, America 2002–03 and 2005–06 Blood samples MET 30/371 (8.1) 6/371 (1.6)
PAP-AUC 26/30 (86.7) SCCmec II 6/6 (100) SCCmec II
4/30 (13.3) others
Rybak et al, 2008[21] USA, America 2003–2007 All clinical samples MET 76/917 (8.3) 3/917 (0.3)
PAP-AUC 43/76 (56.9) SCCmec II
29/76 (38.4) SCCmec IV
4/76 (4.7) others
Delgado et al, 2007[53] Mexico, America 2003/09–2004/08 All clinical samples PAP 1/152 (0.7)
Musta et al, 2009[105] USA, America 2005–2006 Blood samples MHA 21/186 (11.3)
E-test 20/21 (93.0) SCCmec II
1/21 (7.0) SCCmec IV
Kosowska-Shick et al, 2008[57] USA, America 2006/08–2007/12 All clinical samples MET 2/982 (0.2) 3/982 (0.3)
PAP 2/3 (66.7) SCCmec II
1/3 (33.3) SCCmec IV
Hafer et al, 2012[29] USA, America 2007–2008 All clinical samples MIC based 9/77 (11.7) 22/77 (28.6)
PAP-AUC 11/22 (50.0) ST5
11/22 (50.0) ST8
Fink et al, 2012[64] USA, America 2008/02–2010/01 All clinical samples E-test GRD 0/288 (0)
PAP-AUC
Richter et al, 2011[35] USA, America 2009/06–2009/12 All clinical samples E-test GRD 11/4210 (0.4) 0/4210 (0)
PAP-AUC
Silveira et al, 2014[62] Brazil, America 2009/03–2013/02 All clinical samples E-test GRD 12/124 (9.7)
PAP-AUC
Van Hal et al, 2011[37] Australia, Oceania 1997–2008 Blood samples PAP-AUC 54/465 (11.6)54/54 (100) ST239
Charles et al, 2004[24] Australia, Oceania 2001/07–2002/06 Blood samples E-test 5/53 (9.4) 0/53 (0)
PAP-AUC
Horne et al, 2009[89] Australia, Oceania 2005/03–2005/12 All clinical samples MIC based 56/117 (47.9) 2/117 (1.7)
PAP-AUC
Open in a new tab

a BHI: Brain Heart Infusion Agar; PAP: Population Analysis Profile; PAP-AUC: Population Analysis Profile–Area Under the Curve; MET: Macromethod E-test; MHA: Muller Hinton Agar; E-test GRD: E-test Glycopeptide Resistant Detection

Table 2. Prevalence of hVISA and VISA based on study period, origin of study, and isolate selection. a .

Category Subcategory No. Studies No. Strains Prevalence (%) (95% CI)
hVISA Overall 76 99042 6.05 (4.78–7.48)
Study period Before 2006 42 40119 4.68 (3.19–6.41)
2006–2009 10 6485 5.38 (2.40–9.48)
2010–2014 5 680 7.01 (2.12–14.42)
Continent Asia 35 64692 6.81 (4.76–9.16)
Europe-America 41 34350 5.60 (3.85–7.64)
Clinical sample Blood culture sample 21 5944 9.81 (6.71–13.42)
All clinical sample 55 93098 4.68 (3.51–6.00)
VISA Overall 38 68792 3.01 (1.62–4.83)
Study period Before 2006 20 13394 2.05 (0.95–3.55)
2006–2009 4 5630 2.63 (0.29–7.22)
2010–2014 2 2090 7.93 (0.06–26.67)
Continent Asia 18 55362 3.42 (1.10–6.99)
Europe-America 20 13430 2.75 (1.19–4.91)
Clinical sample Blood culture samples 7 2542 2.00 (0.03–6.88)
All clinical samples 31 66250 3.24 (1.67–5.29)
Open in a new tab

CI, confidence interval

a References: [18–108].

Prevalence of hVISA/VISA in different study periods

To analyze the trends in the changes in hVISA/VISA prevalence in recent years, we performed a subgroup analysis of the prevalence of these two types of strains according to the study year. Three periods (before 2006, 2006–2009, and 2010–2014) were designated. Some studies that did not conform to the periods (e.g., reported for 2003–2007) were not included in this analysis.

It can be seen from Table 2 that the prevalence of the hVISA isolates increased gradually from 4.68% (95% CI 3.19–6.41) of 40,119 MRSA strains before 2006 to 5.38% (95% CI 2.40–9.48) of 6485 strains in 2006–2009, reaching 7.01% (95% CI 2.12–14.42) of 680 strains in 2010–2014. The incidence of VISA was 2.05% (95% CI 0.95–3.55) of 13,394 strains before 2006, 2.63% (95% CI 0.29–7.22) of 5,630 strains in 2006–2009, and 7.93% (95% CI 0.06–26.67) of 2090 strains in 2010–2014. Thus, the frequency of VISA during the years 2010–2014 represents a 3.87-fold increase over the years before 2006.

Prevalence of hVISA/VISA at different locations

The prevalence of hVISA/VISA differed among geographic regions in the subgroup analysis, as shown in Table 2. The prevalence of hVISA was 6.81% (95% CI 4.76–9.16) of 64,692 MRSA strains in 35 studies from Asia, and 5.60% (95% CI 3.85–7.64) of 34,350 strains in 41 studies from Europe/America. Moreover, 3.42% (95% CI 1.10–6.99) of 55,362 MRSA strains were VISA in 18 studies from Asia compared with 2.75% (95% CI 1.19–4.91) of 13,430 strains in 20 studies from Europe/America.

Prevalence of hVISA/VISA in different clinical samples

In this subgroup analysis, we divided the MRSA strains into two groups. One group was isolated from only blood culture samples and the other from all clinical samples, including blood, sputum, pus, urine, and so forth (the authors of the original studies did not classify the prevalence rates in the different types of samples). In total, the frequency of hVISA was 9.81% (95% CI 6.71–13.42) in 5944 MRSA strains isolated from blood culture samples reported in 21 studies, significantly higher than in the group of all clinical samples (4.68% [95% CI 3.51–6.00] in 93,098 strains in 55 studies) (P = 0.023). The prevalence rates for VISA were 2.00% (95% CI 0.03–6.88) in 2542 blood-borne MRSA strains in seven studies, and 3.07% (95% CI 1.58–5.02) in 66,250 strains isolated from all clinical samples in another 32 studies (Table 2).

Genetic backgrounds of hVISA/VISA

As shown in Table 3, 25 studies presented information on the genotypes of the hVISA/VISA strains. Sixteen studies that included 685 MRSA strains reported the staphylococcal cassette chromosome mec (SCCmec) types for hVISA. The predominant type was SCCmec II, which accounted for 48.16% of hVISA (95% CI 32.82–63.68), followed by SCCmec IV (18.07%; 95% CI 7.50–31.98) and SCCmec III (17.99%; 95% CI 7.69–31.42). SCCmec I accounted for only 2.12% (95% CI 0.70–4.30). Among the 454 strains from 10 studies that reported multilocus sequence typing (MLST), 11 ST types were identified. ST239 was found in 58.62% (95% CI 22.98–89.73) of hVISA, followed by ST5 in 14.45% (95% CI 4.59–28.53) and ST72 in 3.28% (95% CI 0.98–6.88). The SCCmec types in VISA strains were reported in nine studies, which included 97 strains. SCCmec II was predominant (37.74%, 95% CI 10.01–70.94), followed by SCCmec III (32.72%, 95% CI 3.35–73.85). SCCmec I and SCCmec IV accounted for 11.79% (95% CI 0.01–40.76) and 10.08% (95% CI 1.77–24.05) of isolates, respectively. Six ST types were reported among the VISA strains in 62 strains in six studies. The most prevalent ST types were ST239 (27.05%, 95% CI 2.34–65.22) and ST5 (22.77%, 95% CI 4.66–49.26) (Table 3).

Table 3. Genetic prevalence of hVISA and VISA. a .

Category Subcategory No. Studies No. Strains Prevalence (%) (95% CI)
hVISA SCCmec 16 685
SCCmec I 2.12 (0.70–4.30)
SCCmec II 48.16 (32.82–63.68)
SCCmec III 17.99 (7.69–31.42)
SCCmec IV 18.07 (7.50–31.98)
MLST 10 454
ST239 58.62 (22.98–89.73)
ST5 14.45 (4.59–28.53)
ST72 3.28 (0.98–6.88)
ST59 1.64 (0.28–4.10)
ST900 0.95 (0.13–2.49)
Others (ST1, ST247, ST228, ST398, ST45, ST1301) 9.51 (0.48–27.95)
VISA SCCmec 9 97
SCCmec I 11.79 (0.01–40.76)
SCCmec II 37.74 (10.01–70.94)
SCCmec III 32.72 (3.35–73.85)
SCCmec IV 10.08 (1.77–24.05)
MLST 6 62
ST239 27.05 (2.34–65.22)
ST5 22.77 (4.66–49.26)
Others (ST59, ST72, ST228, ST8) 42.44 (10.44–78.65)
Open in a new tab

CI, confidence interval

aReferences: [21, 26, 28, 29, 33, 44, 46, 52, 55, 59, 65, 70–72, 74, 76, 83, 84, 86, 92, 105]

Discussion

The infections caused by MRSA are problematic because they entail high mortality and only limited antimicrobial drugs are available for their treatment [109]. Vancomycin has generally been the first drug of choice for the treatment of MRSA infections [110]. However, studies have reported that the treatment failure rate for vancomycin is increasing. Takesue et al. studied 128 strains of MRSA causing bacteremia and reported that the efficacy of vancomycin in patients infected with strains with a vancomycin MIC of ≤ 1 μg/ml was 78.8%, whereas it was only 30.0% for patients infected with strains with an MIC of 2 μg/ml [111]. Moore et al. also investigated MRSA bacteremia, and defined treatment failure as a composite of mortality, microbiological failure, and/or the recurrence of infection. The treatment failure rate was 31% in patients infected with 118 MRSA strains with vancomycin MIC > 1 μg/ml [112]. Casapao et al. defined treatment failure as bacteremia for > 7 days or death attributable to MRSA, and observed 64.4% treatment failure in 266 patients with MRSA endocarditis [44]. hVISA and VISA are thought to be among the primary causes of treatment failure. However, in 76 studies (including 99,042 strains) chosen for our analysis, the prevalence of hVISA was only 6.05%, and the prevalence of VISA was only 3.01% in 68,792 strains in 38 studies. Therefore, we speculate that the incidence of hVISA/VISA was underestimated, possibly because of the resistance mechanisms and biological characteristics of these strains. Unlike MRSA and vancomycin-resistant S. aureus (VRSA), the genetic backgrounds associated with hVISA/VISA remain unclear, and a molecular biological method to detect these strains is not yet available. The growth rates of hVISA/VISA are also slow [113, 114]; hence, conventional methods, such as the Kirby–Bauer and instrument-based methods, do not produce accurate results. The PAP-AUC method is considered the gold standard technique for detecting hVISA. However, this method is time-consuming, cumbersome, and unsuitable for clinical laboratories [69], so a significant number of strains may have been missed. Therefore, there is an urgent need for a convenient and effective method with which to detect these strains.

To analyze the trends in the prevalence of hVISA/VISA in recent years, we divided the study period into three periods: before 2006, 2006–2009, and 2010–2014. The first period used the initial resistance breakpoint (vancomycin MIC of 8–16 μg/ml) and the two later periods used the present resistance breakpoint (vancomycin MIC of 4–8 μg/ml). Our study suggests that the prevalence of hVISA/VISA has been increasing in recent years. We consider that the more frequent use of vancomycin for MRSA infections is responsible for this situation because the high prevalence of hVISA/VISA reflects the level of vancomycin use [115, 116]. The inappropriate management of drug-resistant strains has accelerated the spread of hVISA/VISA, and the change in the vancomycin-resistance breakpoint has also contributed to the increase in the prevalence rate.

Since the first reports of hVISA/VISA, the occurrence rates of these strains have varied throughout the world: the incidence of hVISA was 6.81% in Asia and 5.60% in Europe/America, and that of VISA was 3.42% and 2.75%, respectively. Current evidence supports the proposition that hVISA/VISA is more endemic in Asian countries than in Europe/America. Several factors may account for this situation. First, most countries in Europe and America are developed, with high public hygiene standards and scrupulous antimicrobial treatments [69, 101, 102]. Second, the control of nosocomial infections is more successful in European and American countries [41, 95]. Third, Asia is the most populous region of the world, which can create an environment amenable to microbial transmission. The pooled prevalence rate for hVISA in mainland China was 15.78% [58, 71, 83, 84], and in India, the pooled prevalence rates for of hVISA and VISA were 12.41% and 15.09%, respectively [40, 51, 52, 85, 99]. Fourth, because far more MRSA infections occur in Asian countries [117], vancomycin has been used more frequently for their treatment. Therefore, it is not surprising that hVISA and VISA are more common in Asia than elsewhere.

Previous studies have demonstrated that hVISA/VISA are prevalent among bacteremic specimens, and that these strains can persist in the bloodstream for a long time [19]. Our analysis confirms that hVISA is more common in blood-borne MRSAs, consistent with previous opinion. However, the prevalence of VISA was not obviously higher among isolates from blood culture samples than other samples. The reason for this is unclear, but this result suggests that not only blood culture samples but all clinical samples should be given attention.

The mecA gene, which is located within the SCCmec element, is the specific genetic mechanism of methicillin resistance [118]. Many epidemiological studies have demonstrated that community-associated MRSA (CA-MRSA) can be distinguished from hospital-acquired MRSA (HA-MRSA) by the type of the SCCmec element present. The most common SCCmec types in CA-MRSA strains are SCCmec IV and V, whereas SCCmec I, II, and III predominate in HA-MRSA strains [119]. The results of our pooled analysis show that SCCmec II and III were the most prevalent molecular types among the VISA strains. Previous studies have demonstrated limited vancomycin-resistance potential in SCCmec IV MRSA clones [120]. However, we found that the prevalence of SCCmec IV in hVISA was similar to that of SCCmec III. This phenomenon suggests that hVISA is not limited to typical “hospital” clones of S. aureus.

MLST is a powerful and highly discriminatory method for analyzing the population structures and epidemiology of S. aureus [121]. Our study demonstrates that ST239 and ST5 are the most epidemic genotypes of hVISA/VISA. ST239 and ST5 are two international HA-MRSA lineages prevalent in Asia, South America, and Eastern Europe [122, 123]. ST239 MRSA strains are typically resistant to many classes of antibiotics, including β-lactams, fluoroquinolones, aminoglycosides, and macrolide antibiotics. Our results strongly suggest that hVISA and VISA are highly prevalent among international epidemic MRSA strains. Moreover, the genetic backgrounds of these strains are complex, and many ST types are dispersed among hVISA/VISA isolates, including ST59, ST72, and ST900 [70, 72, 74].

The present study had several limitations. Genetic information was available in only 27% (25/91) of the studies we reviewed, which could have led to publication bias and influenced our results. There was also considerable heterogeneity between studies because they differed in various study variables, such as the patient populations examined, testing methodologies used, study durations, previous vancomycin therapy, and concomitant illnesses. These confounding factors could not be circumvented with subgroup analyses. As in previous meta-analyses in which unexplained heterogeneity was identified, we accommodated this condition by using REM, in which the effects underlying the results of different studies are assumed to be drawn from a normal distribution [124]. However, this heterogeneity could not be balanced out by REM alone, so that the stability of the final results must have been affected by the heterogeneity of the sample.

In summary, the results of our study suggest that the prevalence rates of hVISA/VISA have increased in recent years. Our data also supports the view that hVISA/VISA are more prevalent in Asian countries than in Europe/America. Our study confirms that hVISA strains are more common in blood-borne MRSA than in other MRSA. Finally, the most epidemic genotypes of hVISA/VISA are SCCmec II and SCCmec III on SCCmec typing, and ST239 and ST5 on MLST typing, which are predominant among the HA-MRSA strains. However, the incidence of hVISA/VISA is grossly underestimated. Therefore, the detection of hVISA/VISA must be strengthened, especially in samples from patients with bacteremic HA-MRSA infections, and the use of vancomycin and nosocomial infections must be urgently and strictly controlled, particularly in Asian hospitals.

Supporting Information

S1 PRISMA Checklist. PRISMA 2009 checklist.

(DOC)

Click here for additional data file. (64KB, doc)

Data Availability

All relevant data are within the paper.

Funding Statement

The authors have no support or funding to report.

References

  • 1. Lowy FD. Staphylococcus aureus infections. The New England journal of medicine. 1998;339(8):520–32. Epub 1998/08/26. 10.1056/nejm199808203390806 . [DOI] [PubMed] [Google Scholar]
  • 2. M CL, D RS, B-V S, M K, M LG.. Community-associated methicillin-resistant Staphylococcus aureus isolates causing healthcare-associated infections. Emerg Infect Dis. 2007;13(2):236–42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. LC M. Trends in Antimicrobial Resistance in Health Care-Associated Pathogens and Effect on Treatment. Clinical Infectious Diseases. 2006;42(2). [DOI] [PubMed] [Google Scholar]
  • 4. Kaye KS, Engemann JJ, Mozaffari E, Carmeli Y. Reference group choice and antibiotic resistance outcomes. Emerging infectious diseases. 2004;10(6):1125–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. H K.. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. The Lancet Infectious Diseases. 2001;1(3):147–55. [DOI] [PubMed] [Google Scholar]
  • 6. Fridkin SK. Vancomycin-intermediate and -resistant Staphylococcus aureus: what the infectious disease specialist needs to know. Clin Infect Dis. 2001;32(1):108–15. Epub 2000/12/19. 10.1086/317542 . [DOI] [PubMed] [Google Scholar]
  • 7. H K. The emergence of Staphylococcus aureus with reduced susceptibility to vancomycin in Japan. The American Journal of Medicine. 1998;(5A):7S–10S. [DOI] [PubMed] [Google Scholar]
  • 8. R MJ, A RL.. Emergence of methicillin-resistant Staphylococcus aureus with intermediate glycopeptide resistance: clinical significance and treatment options. Drugs. 2001;volume 61(1):1–7(). [DOI] [PubMed] [Google Scholar]
  • 9. Hal SJv, Paterson DL. Systematic review and meta-analysis of the significance of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates. Antimicrob Agents Chemother. 2011;55(1):405–10. 10.1128/AAC.01133-10 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Ariza J, Pujol M, Cabo J, Pena C, Fernandez N, Linares J, et al. Vancomycin in surgical infections due to methicillin-resistant Staphylococcus aureus with heterogeneous resistance to vancomycin. Lancet. 1999;353(9164):1587–8. Epub 1999/05/20. . [DOI] [PubMed] [Google Scholar]
  • 11. Kim MN, Pai CH, Woo JH, Ryu JS, Hiramatsu K. Vancomycin-intermediate Staphylococcus aureus in Korea. Journal of clinical microbiology. 2000;38(10):3879–81. Epub 2000/10/04. ; PubMed Central PMCID: PMCPmc87500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Sng LH, Koh TH, Wang GC, Hsu LY, Kapi M, Hiramatsu K. Heterogeneous vancomycin-resistant Staphylococcus aureus (hetero-VISA) in Singapore. International journal of antimicrobial agents. 2005;25(2):177–9. Epub 2005/01/25. . [DOI] [PubMed] [Google Scholar]
  • 13. Liu C, Chambers HF. Staphylococcus aureus with heterogeneous resistance to vancomycin: epidemiology, clinical significance, and critical assessment of diagnostic methods. Antimicrob Agents Chemother. 2003;47(10):: 3040–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute. 1959;15(4):639–40. [PubMed] [Google Scholar]
  • 15. Dersimonian R, Laird N. N: Meta-analysis in clinical trials. Controlled Clinical Trials. 1986. [DOI] [PubMed] [Google Scholar]
  • 16. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58. Epub 2002/07/12. 10.1002/sim.1186 . [DOI] [PubMed] [Google Scholar]
  • 17. Freeman MF, Tukey JW. Transformations Related to the Angular and the Square Root. ANNALS OF MATHEMATICAL STATISTICS. 1950;6(2):180-. [Google Scholar]
  • 18. Garnier F, Chainier D, Walsh T, Karlsson A, Bolmstrom A, Grelaud C, et al. A 1 year surveillance study of glycopeptide-intermediate Staphylococcus aureus strains in a French hospital. The Journal of antimicrobial chemotherapy. 2006;57(1):146–9. 10.1093/jac/dki413 . [DOI] [PubMed] [Google Scholar]
  • 19. Hanaki H, Cui L, Ikeda-Dantsuji Y, Nakae T, Honda J, Yanagihara K, et al. Antibiotic susceptibility survey of blood-borne MRSA isolates in Japan from 2008 through 2011. Journal of infection and chemotherapy: official journal of the Japan Society of Chemotherapy. 2014;20(9):527–34. . [DOI] [PubMed] [Google Scholar]
  • 20. W SS, H PL, W PC, Y KY.. Bacteremia caused by staphylococci with inducible vancomycin heteroresistance. Clinical Infectious Diseases. 1999;29(4):760–7. [DOI] [PubMed] [Google Scholar]
  • 21. Rybak MJ, Leonard SN, Rossi KL, Cheung CM, Sader HS, Jones RN. Characterization of vancomycin-heteroresistant Staphylococcus aureus from the metropolitan area of Detroit, Michigan, over a 22-year period (1986 to 2007). Journal of clinical microbiology. 2008;46(9):2950–4. 10.1128/JCM.00582-08 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Pastagia M, Kleinman L, Huprikar S, Jenkins S. Clinical and bacteriologic characteristics of a 5-year cohort of MRSA patients at a large U.S. metropolitan hospital. Clinical Microbiology and Infection. 2009;15:S20–S1. [Google Scholar]
  • 23. Fong RK, Low J, Koh TH, Kurup A. Clinical features and treatment outcomes of vancomycin-intermediate Staphylococcus aureus (VISA) and heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) in a tertiary care institution in Singapore. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 2009;28(8):983–7. Epub 2009/04/24. 10.1007/s10096-009-0741-5 . [DOI] [PubMed] [Google Scholar]
  • 24. C PG, W PB, J PD, H BP, G ML.. Clinical Features Associated with Bacteremia Due to Heterogeneous Vancomycin-Intermediate Staphylococcus aureus. Clinical Infectious Diseases. 2004;38(3):448–51. [DOI] [PubMed] [Google Scholar]
  • 25. Maor Y, Hagin M, Belausov N, Keller N, Ben-David D, Rahav G. Clinical features of heteroresistant vancomycin-intermediate Staphylococcus aureus bacteremia versus those of methicillin-resistant S. aureus bacteremia. The Journal of infectious diseases. 2009;199(5):619–24. 10.1086/596629 . [DOI] [PubMed] [Google Scholar]
  • 26. Hsueh PR, Lee SY, Perng CL, Chang TY, Lu JJ. Clonal dissemination of meticillin-resistant and vancomycin-intermediate Staphylococcus aureus in a Taiwanese hospital. International journal of antimicrobial agents. 2010;36(4):307–12. . [DOI] [PubMed] [Google Scholar]
  • 27. Kim MN, Hwang SH, Pyo YJ, Mun HM, Pai CH. Clonal Spread of Staphylococcus aureus Heterogeneously Resistant to Vancomycin in a University Hospital in Korea. Journal of clinical microbiology. 2002;40(4):1376–80. 10.1128/jcm.40.4.1376-1380.2002 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Park KH, Kim ES, Kim HS, Park SJ, Bang KM, Park HJ, et al. Comparison of the clinical features, bacterial genotypes and outcomes of patients with bacteraemia due to heteroresistant vancomycin-intermediate Staphylococcus aureus and vancomycin-susceptible S. aureus. The Journal of antimicrobial chemotherapy. 2012;67(8):1843–9. 10.1093/jac/dks131 . [DOI] [PubMed] [Google Scholar]
  • 29. Hafer C, Lin Y, Kornblum J, Lowy FD, Uhlemann AC. Contribution of selected gene mutations to resistance in clinical isolates of vancomycin-intermediate Staphylococcus aureus. Antimicrobial agents and chemotherapy. 2012;56(11):5845–51. 10.1128/AAC.01139-12 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. dL A, H N, T JF, J-G ML, T G, B A, et al. Control And Outcome Of A Large Outbreak Of Colonization And Infection With Glycopeptide-Intermediate Staphylococcus Aureus In An Intensive Care Unit. Clinical Infectious Diseases. 2006;42(2):170–8. [DOI] [PubMed] [Google Scholar]
  • 31. Kaleem F, Usman J, Amanat S. Current status of Glycopeptide intermediate and heterogenous Glycopeptide intermediate Staphylococcus aureus and their prevailing susceptibility pattern at two tertiary care hospitals of Pakistan. International Journal of Infectious Diseases. 2012;16:e420–e1. 10.1016/j.ijid.2012.05.582 [DOI] [Google Scholar]
  • 32. Robert J, Bismuth R, Jarlier V. Decreased susceptibility to glycopeptides in methicillin-resistant Staphylococcus aureus: a 20 year study in a large French teaching hospital, 1983–2002. The Journal of antimicrobial chemotherapy. 2006;57(3):506–10. 10.1093/jac/dki486 . [DOI] [PubMed] [Google Scholar]
  • 33. Adam HJ, Louie L, Watt C, Gravel D, Bryce E, Loeb M, et al. Detection and characterization of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates in Canada: results from the Canadian Nosocomial Infection Surveillance Program, 1995–2006. Antimicrobial agents and chemotherapy. 2010;54(2):945–9. 10.1128/AAC.01316-09 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. Takata T. Detection of Heterogeneous Vancomycin Intermediate Staphylococcus aureus (hetero-VISA) in MRSA of Japanese Clinical Isolates. American Journal of Infection Control. 2009;37(5):E15–E6. [Google Scholar]
  • 35. Richter SS, Satola SW, Crispell EK, Heilmann KP, Dohrn CL, Riahi F, et al. Detection of Staphylococcus aureus isolates with heterogeneous intermediate-level resistance to vancomycin in the United States. Journal of clinical microbiology. 2011;49(12):4203–7. 10.1128/JCM.01152-11 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, Hori S, et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. The Lancet. 1997;350(9092):1670–3. [DOI] [PubMed] [Google Scholar]
  • 37. Van Hal SJ, Barbagiannakos T, Mercer J, Chen D, Gosbell IB, Paterson DL. Emergence and evolution of heteroresistant vancomycin intermediate Staphylococcus aureus in a single hospital over a 12-year period. Clinical Microbiology and Infection. 2011;17:S58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Song JH, Hiramatsu K, Suh JY, Ko KS, Ito T, Kapi M, et al. Emergence in Asian countries of Staphylococcus aureus with reduced susceptibility to vancomycin. Antimicrobial agents and chemotherapy. 2004;48(12):4926–8. 10.1128/AAC.48.12.4926-4928.2004 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Geisel R, Schmitz FJ, Thomas L, Berns G, Zetsche O, Ulrich B, et al. Emergence of heterogeneous intermediate vancomycin resistance in Staphylococcus aureus isolates in the Dusseldorf area. The Journal of antimicrobial chemotherapy. 1999;43(6):846–8. Epub 1999/07/15. . [DOI] [PubMed] [Google Scholar]
  • 40. Gowrishankar S, Thenmozhi R, Balaji K, Pandian SK. Emergence of methicillin-resistant, vancomycin-intermediate Staphylococcus aureus among patients associated with group A Streptococcal pharyngitis infection in southern India. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2013;14:383–9. 10.1016/j.meegid.2013.01.002 . [DOI] [PubMed] [Google Scholar]
  • 41. Denis O. Emergence of vancomycin-intermediate Staphylococcus aureus in a Belgian hospital: microbiological and clinical features. Journal of Antimicrobial Chemotherapy. 2002;50(3):383–91. 10.1093/jac/dkf142 [DOI] [PubMed] [Google Scholar]
  • 42. SK F. Epidemiological and Microbiological Characterization of Infections Caused by Staphylococcus aureus with Reduced Susceptibility to Vancomycin, United States, 1997–2001. Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America. 2003;36(4):429–39. [DOI] [PubMed] [Google Scholar]
  • 43. Lewis T, Chaudry R, Das I, Lambert P. Epidemiology of MRSA bacteraemia and clinical relevance of reduced susceptibility to vancomycin. Clinical Microbiology and Infection. 2009;15:S544–S5. [Google Scholar]
  • 44. Casapao AM, Davis SL, McRoberts JP, Lagnf AM, Patel S, Kullar R, et al. Evaluation of vancomycin population susceptibility analysis profile as a predictor of outcomes for patients with infective endocarditis due to methicillin-resistant Staphylococcus aureus. Antimicrobial agents and chemotherapy. 2014;58(8):4636–41. 10.1128/AAC.02820-13 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Trakulsomboon S, Danchaivijitr S, Rongrungruang Y, Dhiraputra C, Susaemgrat W, Ito T, et al. First report of methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in Thailand. Journal of clinical microbiology. 2001;39(2):591–5. 10.1128/JCM.39.2.591-595.2001 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Lulitanond A, Engchanil C, Chaimanee P, Vorachit M, Ito T, Hiramatsu K. The first vancomycin-intermediate Staphylococcus aureus strains isolated from patients in Thailand. Journal of clinical microbiology. 2009;47(7):2311–6. 10.1128/JCM.01749-08 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47. K A, R K, S S, T MS, S AR, H MM, et al. Frequency of Reduced Vancomycin Susceptibility and Heterogeneous Subpopulation in Persistent or Recurrent Methicillin-Resistant Staphylococcus aureus Bacteremia. Clin Infect Dis. 2004;38(9):1328–30. [DOI] [PubMed] [Google Scholar]
  • 48. El Ayoubi MD, Hamze M, Mallat H, Achkar M, Dabboussi F. Glycopeptide intermediate Staphylococcus aureus and prevalence of the luk-PV gene in clinical isolates, in Northern Lebanon. Medecine et maladies infectieuses. 2014;44(5):223–8. 10.1016/j.medmal.2014.03.004 . [DOI] [PubMed] [Google Scholar]
  • 49. H SK, M JM, F SK, G RP, J M Jr, T FC.. Glycopeptide-intermediate Staphylococcus aureus: evaluation of a novel screening method and results of a survey of selected U.S. hospitals. Journal of clinical microbiology. 1999;37:: 3590–3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50. M A, B G, T E, D EA, S GC.. Heterogeneous vancomycin resistance in methicillin-resistant Staphylococcus aureus strains isolated in a large Italian hospital. Journal of clinical microbiology. 2000;(2):866–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51. Chaudhari CN, Tandel K, Grover N, Sen S, Bhatt P, Sahni AK, et al. Heterogeneous vancomycin-intermediate among methicillin resistant Staphylococcus aureus. Medical journal, Armed Forces India. 2015;71(1):15–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52. Campanile F, Borbone S, Perez M, Bongiorno D, Cafiso V, Bertuccio T, et al. Heteroresistance to glycopeptides in Italian meticillin-resistant Staphylococcus aureus (MRSA) isolates. International journal of antimicrobial agents. 2010;36(5):415–9. . [DOI] [PubMed] [Google Scholar]
  • 53. Delgado A, Riordan JT, Lamichhane-Khadka R, Winnett DC, Jimenez J, Robinson K, et al. Hetero-vancomycin-intermediate methicillin-resistant Staphylococcus aureus isolate from a medical center in Las Cruces, New Mexico. Journal of clinical microbiology. 2007;45(4):1325–9. 10.1128/JCM.02437-06 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54. Uckay I, Bernard L, Buzzi M, Harbarth S, Francois P, Huggler E, et al. High prevalence of isolates with reduced glycopeptide susceptibility in persistent or recurrent bloodstream infections due to methicillin-resistant Staphylococcus aureus. Antimicrobial agents and chemotherapy. 2012;56(3):1258–64. 10.1128/AAC.05808-11 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55. Wang JL, Lai CH, Lin HH, Chen WF, Shih YC, Hung CH. High vancomycin minimum inhibitory concentrations with heteroresistant vancomycin-intermediate Staphylococcus aureus in meticillin-resistant S. aureus bacteraemia patients. International journal of antimicrobial agents. 2013;42(5):390–4. . [DOI] [PubMed] [Google Scholar]
  • 56. Neoh H-m, Hori S, Komatsu M, Oguri T, Takeuchi F, Cui L, et al. Impact of reduced vancomycin susceptibility on the therapeutic outcome of MRSA bloodstream infections. Annals of Clinical Microbiology and Antimicrobials. 6:13:: 13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57. Kosowska-Shick K, Ednie LM, McGhee P, Smith K, Todd CD, Wehler A, et al. Incidence and characteristics of vancomycin nonsusceptible strains of methicillin-resistant Staphylococcus aureus at Hershey Medical Center. Antimicrobial agents and chemotherapy. 2008;52(12):4510–3. 10.1128/AAC.01073-08 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58. Chen H, Liu Y, Sun W, Chen M, Wang H. The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus correlated with increase of vancomycin MIC. Diagnostic microbiology and infectious disease. 2011;71(3):301–3. . [DOI] [PubMed] [Google Scholar]
  • 59. Reverdy ME, Jarraud S, Bobin-Dubreux S, Burel E, Girardo P, Lina G, et al. Incidence of Staphylococcus aureus with reduced susceptibility to glycopeptides in two French hospitals. Clinical Microbiology and Infection: the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2001;7(5):267–72. [DOI] [PubMed] [Google Scholar]
  • 60. Fitzgibbon MM, Rossney AS, O'Connell B. Investigation of reduced susceptibility to glycopeptides among methicillin-resistant Staphylococcus aureus isolates from patients in Ireland and evaluation of agar screening methods for detection of heterogeneously glycopeptide-intermediate S. aureus. Journal of clinical microbiology. 2007;45(10):3263–9. 10.1128/JCM.00836-07 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61. Nakipoglu Y, Derbentli S, Cagatay AA, Katranci H. Investigation of Staphylococcus strains with heterogeneous resistance to glycopeptides in a Turkish university hospital. BMC infectious diseases. 2005;5:31 10.1186/1471-2334-5-31 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62. Silveira AC, Sambrano GE, Paim TG, Caierao J, Cordova CM, d'Azevedo PA. Is prediffusion test an alternative to improve accuracy in screening hVISA strains and to detect susceptibility to glycopeptides/lipopeptides? Diagnostic microbiology and infectious disease. 2014;79(4):401–4. . [DOI] [PubMed] [Google Scholar]
  • 63. E JM, L C, M M, W EM, P J, G JL, et al. Low colonization prevalence of Staphylococcus aureus with reduced vancomycin susceptibility among patients undergoing hemodialysis in the San Francisco Bay area. Clinical Infectious Diseases. 2005;40(11):1617–24. [DOI] [PubMed] [Google Scholar]
  • 64. Fink SL, Martinello RA, Campbell SM, Murray TS. Low prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates among Connecticut veterans. Antimicrobial agents and chemotherapy. 2012;56(1):582–3. 10.1128/AAC.05024-11 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65. N C, D O, S MJ.. Low prevalence of methicillin-resistant Staphylococcus aureus with reduced susceptibility to glycopeptides in Belgian hospitals. Clinical Microbiology and Infection. 2005;11(3):214–20. [DOI] [PubMed] [Google Scholar]
  • 66. C GL, C M, B D, L M, B A, Bacteriologists AoH, et al. Methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to glycopeptides (GISA) in 63 French general hospitals. Clinical Microbiology and Infection. 2004;10(5):448–51. [DOI] [PubMed] [Google Scholar]
  • 67. Sancak B, Ercis S, Menemenlioglu D, Colakoglu S, Hascelik G. Methicillin-resistant Staphylococcus aureus heterogeneously resistant to vancomycin in a Turkish university hospital. The Journal of antimicrobial chemotherapy. 2005;56(3):519–23. 10.1093/jac/dki272 . [DOI] [PubMed] [Google Scholar]
  • 68. Panomket P, Thirat S, Wanram S, Sranujit RP. Methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in Sanprasitthiprasong Hospital. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2014;97 Suppl 4:S7–11. Epub 2014/05/24. . [PubMed] [Google Scholar]
  • 69. W M, H RA, H R, W TR, B PM, M AP.. A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital. Journal of Antimicrobial Chemotherapy. 2001;47(4):399–403. [DOI] [PubMed] [Google Scholar]
  • 70. Wang WY, Lee SY, Chiueh TS, Lu JJ. Molecular and phenotypic characteristics of methicillin-resistant and vancomycin-intermediate staphylococcus aureus isolates from patients with septic arthritis. Journal of clinical microbiology. 2009;47(11):3617–23. 10.1128/JCM.00539-09 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71. Liu C, Chen ZJ, Sun Z, Feng X, Zou M, Cao W, et al. Molecular characteristics and virulence factors in methicillin-susceptible, resistant, and heterogeneous vancomycin-intermediate Staphylococcus aureus from central-southern China. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi. 2014. . [DOI] [PubMed] [Google Scholar]
  • 72. Lin SY, Chen TC, Chen FJ, Chen YH, Lin YI, Siu LK, et al. Molecular epidemiology and clinical characteristics of hetero-resistant vancomycin intermediate Staphylococcus aureus bacteremia in a Taiwan Medical Center. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi. 2012;45(6):435–41. . [DOI] [PubMed] [Google Scholar]
  • 73. Kim HB, Park WB, Lee KD, Choi YJ, Park SW, Oh Md, et al. Nationwide Surveillance for Staphylococcus aureus with Reduced Susceptibility to Vancomycin in Korea. Journal of clinical microbiology. 2003;41(6):2279–81. 10.1128/jcm.41.6.2279-2281.2003 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74. Chung G, Cha J, Han S, Jang H, Lee K, Yoo J, et al. Nationwide surveillance study of vancomycin intermediate Staphylococcus aureus strains in Korean hospitals from 2001 to 2006. Journal of microbiology and biotechnology. 2010;20(3):637–42. Epub 2010/04/08. . [PubMed] [Google Scholar]
  • 75. Ike Y, Arakawa Y, Ma X, Tatewaki K, Nagasawa M, Tomita H, et al. Nationwide survey shows that methicillin-resistant Staphylococcus aureus strains heterogeneously and intermediately resistant to vancomycin are not disseminated throughout Japanese hospitals. Journal of clinical microbiology. 2001;39(12):4445–51. 10.1128/JCM.39.12.4445-4451.2001 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76. Hanaki H, Hososaka Y, Yanagisawa C, Otsuka Y, Nagasawa Z, Nakae T, et al. Occurrence of vancomycin-intermediate-resistant Staphylococcus aureus in Japan. Journal of infection and chemotherapy: official journal of the Japan Society of Chemotherapy. 2007;13(2):118–21. . [DOI] [PubMed] [Google Scholar]
  • 77. Sader HS, Jones RN, Rossi KL, Rybak MJ. Occurrence of vancomycin-tolerant and heterogeneous vancomycin-intermediate strains (hVISA) among Staphylococcus aureus causing bloodstream infections in nine USA hospitals. The Journal of antimicrobial chemotherapy. 2009;64(5):1024–8. 10.1093/jac/dkp319 . [DOI] [PubMed] [Google Scholar]
  • 78. Parer S, Lotthe A, Chardon P, Poncet R, Jean-Pierre H, Jumas-Bilak E. An outbreak of heterogeneous glycopeptide-intermediate Staphylococcus aureus related to a device source in an intensive care unit. Infection control and hospital epidemiology. 2012;33(2):167–74. 10.1086/663703 . [DOI] [PubMed] [Google Scholar]
  • 79. N A, L NL, K AG, S N.. The presence of heterogeneous vancomycin-lntermediate Staphylococcus aureus (heteroVISA) in a major Malaysian hospital. The Medical journal of Malaysia. 2012;(3). [PubMed] [Google Scholar]
  • 80. B G, F K, L W, S C, S HG.. Presence of Staphylococcus aureus with Reduced Susceptibility to Vancomycin in Germany. European Journal of Clinical Microbiology and Infectious Diseases. 1999;18(10):691–6. [DOI] [PubMed] [Google Scholar]
  • 81. Ho CM, Hsueh PR, Liu CY, Lee SY, Chiueh TS, Shyr JM, et al. Prevalence and accessory gene regulator (agr) analysis of vancomycin-intermediate Staphylococcus aureus among methicillin-resistant isolates in Taiwan—SMART program, 2003. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 2010;29(4):383–9. 10.1007/s10096-009-0868-4 . [DOI] [PubMed] [Google Scholar]
  • 82. Maor Y, Rahav G, Belausov N, Ben-David D, Smollan G, Keller N. Prevalence and characteristics of heteroresistant vancomycin-intermediate Staphylococcus aureus bacteremia in a tertiary care center. Journal of clinical microbiology. 2007;45(5):1511–4. 10.1128/JCM.01262-06 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83. Sun W, Chen H, Liu Y, Zhao C, Nichols WW, Chen M, et al. Prevalence and characterization of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates from 14 cities in China. Antimicrobial agents and chemotherapy. 2009;53(9):3642–9. 10.1128/AAC.00206-09 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84. W Y, H YJ, A XM, X HT, S TY.. Prevalence and clinical prognosis of heteroresistant vancomycin-intermediate Staphylococcus aureus in a tertiary care center in China. Chin Med J (Engl). 2013;126(3):505–9. [PubMed] [Google Scholar]
  • 85. Chaudhary M, Payasi A. Prevalence of heterogeneous glycopeptide intermediate resistance in Methicillin-Resistant Staphylococcus aureus. American Journal of Infectious Diseases. 2013;9(3):63–70. [Google Scholar]
  • 86. Vaudaux P, Ferry T, Uckay I, Francois P, Schrenzel J, Harbarth S, et al. Prevalence of isolates with reduced glycopeptide susceptibility in orthopedic device-related infections due to methicillin-resistant Staphylococcus aureus. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 2012;31(12):3367–74. 10.1007/s10096-012-1705-8 . [DOI] [PubMed] [Google Scholar]
  • 87. Khanal B, Baral R, Acharya A. Prevalence of Vancomycin Intermediate Staphyloccus aureus (VISA) in a tertiary care hospital in Eastern Nepal. International Journal of Infectious Diseases. 2010;14:e342–e3. [Google Scholar]
  • 88. Bert F, Clarissou J, Durand F, Delefosse D, Chauvet C, Lefebvre P, et al. Prevalence, Molecular Epidemiology, and Clinical Significance of Heterogeneous Glycopeptide-Intermediate Staphylococcus aureus in Liver Transplant Recipients. Journal of clinical microbiology. 2003;41(11):5147–52. 10.1128/jcm.41.11.5147-5152.2003 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89. Horne KC, Howden BP, Grabsch EA, Graham M, Ward PB, Xie S, et al. Prospective comparison of the clinical impacts of heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-susceptible MRSA. Antimicrobial agents and chemotherapy. 2009;53(8):3447–52. 10.1128/AAC.01365-08 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 90. Canton R, Mir N, Martinez-Ferrer M, Sanchez del Saz B, Soler I, Baquero F. [Prospective study of Staphylococcus aureus with reduced susceptibility to glycopeptides]. Revista espanola de quimioterapia: publicacion oficial de la Sociedad Espanola de Quimioterapia. 1999;12(1):48–53. Epub 2000/07/15. . [PubMed] [Google Scholar]
  • 91. K M, T PT, T-K A, L NJ, V AC.. Reduced susceptibility to vancomycin of nosocomial isolates of methicillin-resistant Staphylococcus aureus. The Journal of antimicrobial chemotherapy. 1999;43(5):729–31. [DOI] [PubMed] [Google Scholar]
  • 92. Khatib R, Jose J, Musta A, Sharma M, Fakih MG, Johnson LB, et al. Relevance of vancomycin-intermediate susceptibility and heteroresistance in methicillin-resistant Staphylococcus aureus bacteraemia. The Journal of antimicrobial chemotherapy. 2011;66(7):1594–9. 10.1093/jac/dkr169 . [DOI] [PubMed] [Google Scholar]
  • 93. Bataineh HA. Resistance of Staphylococcus aureus to vancomycin in Zarqa, Jordan. Pakistan Journal of Medical Sciences. 2006;22(2):144–8. [Google Scholar]
  • 94. Ramli SR, Neoh HM, Aziz MN, Hussin S. Screening and detection of heterogenous vancomycin intermediate Staphylococcus aureus in Hospital Kuala Lumpur Malaysia, using the glycopeptide resistance detection Etest and population analysis profiling. Infectious disease reports. 2012;4(1):e20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 95. Pierard D, Vandenbussche H, Verschraegen I, Lauwers S. [Screening for Staphylococcus aureus with a reduced susceptibility to vancomycin in: a Belgian hospital]. Pathologie-biologie. 2004;52(8):486–8. 10.1016/j.patbio.2004.07.016 . [DOI] [PubMed] [Google Scholar]
  • 96. Mlynarczyk A, Mlynarczyk G, Luczak M. [Searching for Staphylococcus aureus strains with reduced susceptibility to glycopeptides among clinical isolates obtained during the year of 2002]. Medycyna doswiadczalna i mikrobiologia. 2003;55(3):209–17. Epub 2004/01/02. . [PubMed] [Google Scholar]
  • 97. F D, C MW, W AH, E MB, W RP.. Seeking Vancomycin Resistant Staphylococcus aureus among Patients with Vancomycin-Resistant Enterococci. Clinical Infectious Diseases. 1999;29(6):1566–8. [DOI] [PubMed] [Google Scholar]
  • 98. Kirby A, Graham R, Williams NJ, Wootton M, Broughton CM, Alanazi M, et al. Staphylococcus aureus with reduced glycopeptide susceptibility in Liverpool, UK. The Journal of antimicrobial chemotherapy. 2010;65(4):721–4. 10.1093/jac/dkq009 . [DOI] [PubMed] [Google Scholar]
  • 99. Dubey D, Rath S, Sahu MC, Pattnaik L, Debata NK, Padhy RN. Surveillance of infection status of drug resistant Staphylococcus aureus in an Indian teaching hospital. Asian Pacific Journal of Tropical Disease. 2013;3(2):133–42. 10.1016/s2222-1808(13)60057-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 100. Guo Y, Wang H, Zhao CJ, Wang ZW, Cao B, Xu YC, et al. A surveillance study of antimicrobial resistance of gram-positive cocci strains isolated from 16 teaching hospitals in China in 2012. Chinese Journal of Microbiology and Immunology (China). 2013;33(6):401–9. [Google Scholar]
  • 101. Schmitz F-J, Krey A, Geisel R, Verhoef J, Heinz H-P, Fluit AC. Susceptibility of 302 methicillin-resistant Staphylococcus aureus isolates from 20 European university hospitals to vancomycin and alternative antistaphylococcal compounds. European Journal of Clinical Microbiology and Infectious Diseases. 1999;18(7):528–30. [DOI] [PubMed] [Google Scholar]
  • 102. A HM, W M, G M, J AP, R JF, C BD, et al. Twenty months of screening for glycopeptide-intermediate Staphylococcus aureus. The Journal of antimicrobial chemotherapy. 2000;46(4):639–40. [DOI] [PubMed] [Google Scholar]
  • 103. S B, Y S, G D, G Z, O D, S G, et al. Vancomycin and daptomycin minimum inhibitory concentration distribution and occurrence of heteroresistance among methicillin-resistant Staphylococcus aureus blood isolates in Turkey. BMC infectious diseases. 2013;13(50):46–54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 104. Ariza J, Pujol M, Cabo J, Peña C, Fernández N, Liñares J, et al. Vancomycin in surgical infections due to meticillin-resistant Staphylococcus aureus with heterogeneous resistance to vancomycin. The Lancet. 1999;353(9164):1587–8. [DOI] [PubMed] [Google Scholar]
  • 105. Musta AC, Riederer K, Shemes S, Chase P, Jose J, Johnson LB, et al. Vancomycin MIC plus heteroresistance and outcome of methicillin-resistant Staphylococcus aureus bacteremia: trends over 11 years. Journal of clinical microbiology. 2009;47(6):1640–4. 10.1128/JCM.02135-08 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 106. Tallent SM, Bischoff T, Climo M, Ostrowsky B, Wenzel RP, Edmond MB. Vancomycin Susceptibility of Oxacillin-Resistant Staphylococcus aureus Isolates Causing Nosocomial Bloodstream Infections. Journal of clinical microbiology. 2002;40(6):2249–50. 10.1128/jcm.40.6.2249-2250.2002 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 107. Pitz AM, Yu F, Hermsen ED, Rupp ME, Fey PD, Olsen KM. Vancomycin susceptibility trends and prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus in clinical methicillin-resistant S. aureus isolates. Journal of clinical microbiology. 2011;49(1):269–74. 10.1128/JCM.00914-10 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 108. Kim MN, Pai CH, Woo JH, Ryu JS, Hiramatsu K. Vancomycin-intermediate Staphylococcus aureus in Korea. Journal of clinical microbiology. 2000;38(10):3879–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 109. Pastagia M, Kleinman LC, Cruz EGLdl, Jenkins SG. Predicting risk for death from MRSA bacteremia. Emerging Infectious Diseases. 2012;18(7):1072–80. 10.3201/eid1807.101371 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 110. CG G. Glycopeptide resistance in Staphylococcus aureus: is it a real threat? Journal of infection and chemotherapy: official journal of the Japan Society of Chemotherapy. 2004;10(2):69–75. [DOI] [PubMed] [Google Scholar]
  • 111. T Y, N K, T Y, I K, I M, W Y, et al. Clinical characteristics of vancomycin minimum inhibitory concentration of 2 μg/ml methicillin-resistant Staphylococcus aureus strains isolated from patients with bacteremia. Journal of Infection and Chemotherapy. 2011;17(1):52–7. [DOI] [PubMed] [Google Scholar]
  • 112. Moore CL, Osaki-Kiyan P, Haque NZ, Perri MB, Donabedian S, Zervos MJ. Daptomycin versus vancomycin for bloodstream infections due to methicillin-resistant Staphylococcus aureus with a high vancomycin minimum inhibitory concentration: a case-control study. Clin Infect Dis. 2012;54(1):51–8. Epub 2011/11/24. 10.1093/cid/cir764 . [DOI] [PubMed] [Google Scholar]
  • 113. Tenover FC, Biddle JW, Lancaster MV. Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus. Emerg Infect Dis. 2001;7(2):327–32. Epub 2001/04/11. ; PubMed Central PMCID: PMCPmc2631729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 114. Saito M, Katayama Y, Hishinuma T, Iwamoto A, Aiba Y, Kuwahara-Arai K, et al. "Slow VISA," a novel phenotype of vancomycin resistance, found in vitro in heterogeneous vancomycin-intermediate Staphylococcus aureus strain Mu3. Antimicrobial agents and chemotherapy. 2014;58(9):5024–35. Epub 2014/05/21. 10.1128/aac.02470-13 ; PubMed Central PMCID: PMCPmc4135821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 115. Ho PL, Lo PY, Chow KH, Lau EH, Lai EL, Cheng VC, et al. Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong. The Journal of infection. 2010;60(2):140–5. Epub 2009/12/08. . [DOI] [PubMed] [Google Scholar]
  • 116. Chang W, Ma X, Gao P, Lv X, Lu H, Chen F. Vancomycin MIC creep in methicillin-resistant Staphylococcus aureus (MRSA) isolates from 2006 to 2010 in a hospital in China. Indian journal of medical microbiology. 2015;33(2):262–6. Epub 2015/04/14. 10.4103/0255-0857.148837 . [DOI] [PubMed] [Google Scholar]
  • 117. Chen CJ, Huang YC. New epidemiology of Staphylococcus aureus infection in Asia. Clin Microbiol Infect. 2014;20(7):605–23. Epub 2014/06/04. 10.1111/1469-0691.12705 . [DOI] [PubMed] [Google Scholar]
  • 118. K Y, I T, H K.. A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrobial agents and chemotherapy. 2000;44(6):: 1549–55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 119. N TS, L KH, C-S K, B SM, B DJ, E J, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003;290(22):2976–84. [DOI] [PubMed] [Google Scholar]
  • 120. K SL, M WJ, N GR.. In vitro exposure of community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains to vancomycin: does vancomycin resistance occur? International journal of antimicrobial agents. 2006;27(2):168–70. [DOI] [PubMed] [Google Scholar]
  • 121. E J, E-G C, S I, L AR, G L.. Carriage frequency, diversity and methicillin resistance of Staphylococcus aureus in Danish small ruminants. Veterinary Microbiology. 2013;163:110–5. 10.1016/j.vetmic.2012.12.006 [DOI] [PubMed] [Google Scholar]
  • 122. Aires de Sousa M, Conceicao T, Simas C, de Lencastre H. Comparison of genetic backgrounds of methicillin-resistant and -susceptible Staphylococcus aureus isolates from Portuguese hospitals and the community. Journal of clinical microbiology. 2005;43(10):5150–7. Epub 2005/10/07. 10.1128/jcm.43.10.5150-5157.2005 ; PubMed Central PMCID: PMCPmc1248511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 123. L M, D X, V AE, D BA, W D, S Y, et al. MRSA epidemic linked to a quickly spreading colonization and virulence determinant. Nature Medicine. 2012;18(5):816–9. 10.1038/nm.2692 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 124. JP H. A re-evaluation of random-effects meta-analysis. J R Stat Soc Ser A Stat Soc. 2009;172(1):137–59. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 PRISMA Checklist. PRISMA 2009 checklist.

(DOC)

Click here for additional data file. (64KB, doc)

Data Availability Statement

All relevant data are within the paper.

Articles from PLoS ONE are provided here courtesy of PLOS

RESOURCES