Title: Prevalence of vancomycin‐resistant enterococci in Asia—A systematic review and meta‐analysis
Abstract: Journal of Clinical Pharmacy and TherapeuticsEarly View REVIEW ARTICLE Free Access Prevalence of vancomycin-resistant enterococci in Asia—A systematic review and meta-analysis Suraj Shrestha MBBS, Corresponding Author [email protected] orcid.org/0000-0001-6888-260X Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal Correspondence Suraj Shrestha, MBBS, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal. Email: [email protected] for more papers by this authorSanjeev Kharel MBBS, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, NepalSearch for more papers by this authorSushan Homagain MBBS, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, NepalSearch for more papers by this authorRoshan Aryal MBBS, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, NepalSearch for more papers by this authorShyam Kumar Mishra PhD, orcid.org/0000-0002-3888-7319 Department of Microbiology, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal School of Optometry and Vision Science, UNSW Sydney, AustraliaSearch for more papers by this author Suraj Shrestha MBBS, Corresponding Author [email protected] orcid.org/0000-0001-6888-260X Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal Correspondence Suraj Shrestha, MBBS, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal. Email: [email protected] for more papers by this authorSanjeev Kharel MBBS, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, NepalSearch for more papers by this authorSushan Homagain MBBS, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, NepalSearch for more papers by this authorRoshan Aryal MBBS, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, NepalSearch for more papers by this authorShyam Kumar Mishra PhD, orcid.org/0000-0002-3888-7319 Department of Microbiology, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal School of Optometry and Vision Science, UNSW Sydney, AustraliaSearch for more papers by this author First published: 25 February 2021 https://doi.org/10.1111/jcpt.13383 AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract What is known and objective The rise of vancomycin-resistant enterococci (VRE) has been a major health problem in most countries of the world including Asia, since its discovery. There is a paucity of data on VRE in many countries of Asia as well as limited pooled estimates. Therefore, we performed a systematic review and meta-analysis to estimate a pooled prevalence of VRE in Asia. Methods A literature search in electronic databases like PubMed, Embase and Google Scholar and manual searching of references and grey literature, comprising the information on the prevalence of VRE with at least two species of enterococci, conducted in different countries of Asia from January 1, 2000, to September 20, 2020, was done. The random-effect model and 95% CIs was used to calculate the pooled prevalence. Subgroup, sensitivity and meta-regression analyses were performed to address heterogeneity while Egger's test for publication bias. Results and Discussions We identified 39 studies, comprising a total of 11,875 enterococcal isolates. The result of the analysis showed that the pooled prevalence of VRE in Asia was 8.10% (95% CI; 7–9; I2 = 93.79%; p < 0.001). Resistance to vancomycin was greater among strains of E. faecium compared to the strains of E. faecalis (22.40% vs. 3.70%). Amongst various regions of Asia, the highest prevalence of VRE was found in the Western Asian region and the lowest in the South-east Asian region. Moreover, the rate of VRE was higher than most European countries and lower than USA. What is new and Conclusions With an upsurge of VRE in Asia in recent years, efficient infection control programmes, robust surveillance systems and adherence to antibiotic stewardship are paramount to halt the further rise of VRE. 1 WHAT IS KNOWN AND OBJECTIVE Enterococci are gram-positive flora of the human intestine, of which E. faecalis and E. faecium are responsible for the majority of the infections in humans amongst at least 59 validly published species.1, 2 They are common causes of some serious infections such as endocarditis, urinary tract infection, wound infection and nosocomial bacteremia.3-5 Enterococci are resistant to a wide range of antimicrobials used in the treatment of gram-positive bacterial infection and inherent resistance is shown to aminoglycosides, clindamycin and co-trimoxazole.3, 6 They also have the ability for the acquisition of resistant genes to antimicrobials through mutations or attainment of genetic materials like plasmids and transposons and transmission by conjugation or other transfer methods of resistant genes.7 Their eradication can be extremely difficult as they can also form biofilms that contribute to virulence, resistance to antimicrobials and phagocytosis.8, 9 Vancomycin, which had been in use since the 1950s, was used as the last line of defence for the treatment of multidrug-resistant enterococci (MDR).10 Vancomycin resistance in enterococci is usually an acquired feature as a result of mutation or gain of resistant genetic materials.3, 6, 11 However, E. gallinarum and E. casseliflavus are intrinsically resistant to vancomycin at concentrations typically lower than or equal to 32 μg/ml.6 Resistance against vancomycin, which was first reported in England and France in the 1980s, has now spread rapidly.12 The rate of vancomycin resistance in the United States hospitals by 2002 was 60% of E. faecium and 2% of E. faecalis.13 The figures climbed further to 80% in E. faecium and 7% in E. faecalis by 2007.5 In Asia, vancomycin-resistant enterococci (VRE) was first reported in Singapore in 1994.14 As the therapeutic choices are extremely limited because of the resistance to multiple antibiotics, VRE has been recognized as a global public health problem.4, 15 Significant level of VRE colonization might be found among persons not related to the health care settings because VRE from animal sources and humans foods of animal origin play a huge part in colonization and infection in humans.16 Infections due to VRE have been reported to be linked with increased rates of morbidity, mortality, a longer length of hospital stays, higher healthcare expenses due to the reduced number of therapeutic options and the patients infected with resistant organisms require a higher frequency of surgical interventions for infection control.17-20 The rise of VRE strains has caused numerous problems for patients all over the world including Asia.21 With the drug-resistant microorganisms striking several problems for healthcare systems and scarcity of new data related to vancomycin resistance in enterococci species in Asia, along with absence of inclusive reviews of VRE covering different sub regions of Asia, this study was conducted to update the findings of studies to estimate the current burden of VRE in Asia. 2 METHODS 2.1 Literature search strategy A systematic literature search of databases like PubMed, Embase and Google Scholar to identify all the relevant published articles from 2000 till September 20, 2020, was conducted by two independent authors (SS and SK). PubMed search was conducted using MeSH terms and keywords "Enterococcus faecalis", "Enterococcus faecium", "Vancomycin resistan*", "Antibiotic resistan*", "epidemiology" and "prevalence" along with all the names of all the Asian countries using suitable Boolean operators. Similarly, an Embase search was conducted using Emtree terms and names of Asian countries with suitable combinations. Besides, all the references of the included full texts and various reviews were thoroughly screened for any additional studies. Authors of some studies were contacted via email and ResearchGate for retrieval of full texts and clarification of doubts wherever required. The search strategy employed for this study is detailed in the supplementary document. (Appendix S1). Studies obtained from the electronic databases, supplementary sources, manual searching, grey literature sites and other repositories were exported to endnote reference software version 9.1 (Thomson Reuters) in the compatible formats. Duplicate articles were screened first by endnote and then manually. Duplicates were then recorded and removed. For multiple publications of the same data in more than one journal, the most inclusive, comprehensive studies, with larger sample size, and the most recent ones were considered. The systematic review and meta-analysis were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PRISMA diagram detailing the selection process is shown in Figure 1. FIGURE 1Open in figure viewerPowerPoint PRISMA diagram of the study identification and selection process 2.2 Inclusion and exclusion criteria All articles published in English were considered eligible for inclusion if: Cross-sectional studies conducted in Asian countries in any setting. VRE isolated from clinical specimens (ie at least two enterococci species) of patients only. Sample size more than 100 to minimize the potential bias caused by an inadequate sample size Use of standard methods for VRE detection: Disk diffusion method, polymerase chain reaction (PCR), E test, microdilution (agar and broth), minimum inhibitory concentration (MIC), VTEK. Studies published from January 1 2000 to September 20, 2020. While the following articles were excluded from our review. Studies with insufficient information Studies other than cross-sectional studies Studies assessing antimicrobial susceptibility in other organisms except for enterococci Review studies, Conference abstracts, articles published in languages other than English, Editorials and letters along with Outbreak and Surveillance studies and trend analysis study. Studies on antimicrobial susceptibility tests other than vancomycin. VRE isolates from healthy individuals, environment, animals or water disposal or any other non-human source. No accessible full texts Studies with VRE surviving in special disease groups (eg HIV-positive or any other immunodeficient patients, cancer groups and transplant cases) and Studies with incomplete outcomes of interest. 2.3 Literature screening, data extraction and quality assessment All the titles and abstracts retrieved by searching available literature were screened independently by two authors (SS and SH) against the eligibility criteria. Various information extracted from the eligible articles included the first author, year of publication, country of study, study design, study period, the total number of enterococci isolates (along with the species if available), the total number of vancomycin-resistant enterococci (along with the species if available) and method used for antibiotic susceptibility test and recorded in Microsoft Excel version 2013 (Microsoft Corp). Any disagreement was resolved by mutual consensus with the author (SK). Since all the studies were all cross-sectional studies, the quality assessment was done by two authors (SS and SH) using a modified Newcastle-Ottawa scale (NOS) (Appendix S3). Any disagreement was resolved by consulting with the author (SK) whenever necessary. 2.4 Statistical analysis The data collected in the Excel sheet were exported, and analysis was performed using the stata software version 16 (StataCorp). Prevalence estimates of VRE were calculated by pooling the study-specific estimates with its 95% confidence interval using the random-effects model by Der Simonian and Laird's random-effects model. Heterogeneity of VRE prevalence of the included studies was examined using the Cochrane Q test and I2 statistic (I2 of less than 25% defined as mild heterogeneity, I2 of 25%–50% as moderate heterogeneity and I2 of more than 50% as severe heterogeneity). Subgroup analyses for VRE prevalence by regions of Asia, enterococci species, detection method and study years were carried out where data were available to address the heterogeneity. Moreover, meta-regression was conducted to detect the main source of heterogeneity. A p-value of <0.05 was considered statistically significant. Sensitivity analyses were performed by serially excluding each study to determine the effect of individual studies on the degree of heterogeneity (Appendix S3). The publication bias was assessed by Egger's regression test for small study effect size and shown in a funnel plot of standard error and effect size. A p-value of <0.10 was considered as statistically significant publication bias. 3 RESULTS 3.1 Study selection and characteristics The initial search yielded 1209 articles by searching various databases for published articles including preprint articles. After the removal of the duplicate articles, 1102 articles were screened from the title and abstract and 151 full-text articles were reviewed for eligibility, and finally, 39 studies were included for the systematic review and meta-analysis. All of the included studies were cross-sectional studies. Of the 39 studies which met our eligibility criteria, 12 studies were from Iran, another 12 studies from India, 5 studies from China and others from various Asian countries. A total of 11,875 enterococci isolates were examined for the VRE by various methods from various clinical specimens in the clinical settings. Thirty-six studies reported the enterococcal isolates at the species level and thirty-four studies reported the VRE isolates at the species level. Of 11,875 enterococci isolates, species of 1977 enterococci were not identified. We found that 53.19% (6316) of the total enterococcal isolates belonged to E. faecalis, 24.19% (2873) belonged to E. faecium and 5.97% (709) belonged to other species while 16.64% (1977) were not classified according to species. The prevalence of the VRE ranged from 1% to as high as 27.70%. Details of the characteristics of the included studies are summarized in Table 1. TABLE 1. Characteristics of the studies included in the review Authors Publication year Country of Study Total Enterococci isolates Total E. faecalis isolates Total E. faecium isolates Specimen Method VRE number E. faecalis VRE E. faecium VRE Akhi et al. 2009 Iran 137 124 8 Urine, Ascitic fluid, Wound, Catheter, Blood Disk diffusion 6 1/124 (0.81%) 3/8 (37.50%) Aligholi et al. 2009 Iran 495 320 157 NA Agar dilution 23 4/320 (1.25%) 19/157 (12.10%) Alotaibi et al. 2017 Saudi Arabia 231 168 53 Blood, Urine, Wound swab Disk diffusion 40 2/168 (1.19%) 33/53 (62.26%) Altalib et al. 2015 Malaysia 222 183 39 Blood, Urine, Sputum, Stool E test 7 NA NA Alyesian et al. 2007 Iran 126 108 11 Urine, Blood, Wound, Catheter, dialysis fluid Disk diffusion 12 7/108 (6.48%) 5/11 (45.45%) Ejaz et al. 2019 Pakistan 147 139 8 Urine. Pus, Wound swab Disk diffusion 4 4/139 (2.88%) 0 Emaneini et al. 2008 Iran 326 210 116 Urine, Blood, Wound Disk diffusion 38 8/210 (3.81%) 30/116 (25.86%) Fernandes et al. 2013 India 150 84 51 Urine, Pus, Sputum, Blood, Vaginal swabs Agar dilution 13 4/84 (4.76%) 6/51 (11.76%) Ghosal et al. 2006 India 685 456 229 Urine, Pus, Bile Disk diffusion 10 0 10/229 (4.37%) Goel et al. 2016 India 115 61 42 Urine Disk diffusion 16 8/61 (13.11%) 6/42 (14.29%) Haghi et al. 2019 Iran 100 69 10 Urine Agar dilution 21 0 7/10 (70%) Hasemi et al. 2006 Iran 120 68 36 Urine Agar dilution 8 3/68 (4.41%) 2/36 (5.56%) Ibrahim et al. 2011 Malaysia 585 NA NA Urine, Blood, Pus, Wound swab Disk diffusion 6 1 4 Jahansepas et al. 2017 Iran 160 125 35 Urine, Blood, Wound E test 30 11/125 (8.8%) 19/35 (54.29%) Li et al. 2007 China 338 234 86 Blood, Urine, Bile E test 11 4/234 (1.71%) 1/86 (1.16%) Mahafzah et al. 2008 Jordan 177 147 28 Wound, Urine, Blood, Peritoneal Fluid E test 7 6/147 (4.08%) 1/28 (3.57%) Mathew et al. 2018 India 156 135 18 Urine, Blood, CSF, Body fluids, Pus E test 15 13/135 (9.63%) 2/18 (11.11%) Modi et al. 2012 India 250 145 105 Urine, Blood, wound, Pus Disk diffusion 10 2/10 (1.38%) 8/10 (7.62%) Maradia et al. 2016 India 156 50 106 Urine Disk diffusion 5 NA NA Nasaj et al. 2015 Iran 280 175 67 Urine, Blood, wound, Body fluids Disk Diffusion 60 9/175 (5.14%) 51/67 (76.12%) Phukan et al. 2016 India 67 54 13 Blood, Sputum, Pus Disk Diffusion 16 9/54 (16.67%) 7/13 (53.84%) Purohit et al 2017 India 250 82 162 Blood, Pus, Urine E test 57 2/82 (2.44%) 55/162 (33.95%) Saifi et al. 2007 Iran 638 496 142 Urine Disk diffusion 106 17/496 (3.42%) 89/142 (62.68%) Salem et al. 2012 Saudi Arabia 206 166 27 Wound, Urine, Blood, Stool E test 8 3/166 (1.81%) 5/27 (18.52%) Sami et al. 2020 India 1014 NA NA Pus, Urine Disk diffusion 31 1 30 Shahi et al. 2020 Iran 119 17 72 Urine, Blood, Ascites Fluid Disk diffusion 33 NA NA Sheikh et al. 2019 Iran 120 15 73 Urine, Wound, Blood Disk diffusion 31 NA NA Shokuhizadeh et al. 2018 Iran 56 35 21 Wound, Blood, Urine Disk diffusion 5 0 5/21 (23.81%) Somily et al. 2016 Saudi Arabia 378 NA NA Blood, Urine E test 17 0 13 Taneja et al. 2004 India 144 80 17 Urine Agar dilution 8 1/80 (1.25%) 5/17 (29.41%) Tripathi et al. 2016 India 1488 1067 421 Urine, Blood, Pus Disk diffusion 118 72/1067 (6.75%) 46/421 (10.93%) Udo et al. 2002 Kuwait 415 354 32 Urine, Blood, Wound swabs, Stool. Disk diffusion 11 7/354 (1.98%) 4/32 (12.5%) Wang et al. 2014 China 517 252 265 Urine Broth Based microdilution 54 12/252 (4.76%) 42/265 (15.85%) Wang et al. 2018 China 814 242 245 Urine Disk Diffusion 8 NA NA Xiao et al. 2015 China 98 51 40 Urine Agar dilution 1 0 1/40 (2.5%) Yadav et al. 2017 India 200 169 27 Urine, Blood, Pus Disk diffusion 14 14/169 (8.28%) 0 Yameen et al. 2013 Pakistan 85 40 45 Nasal, Perirectal swab Disk diffusion 9 5/40 (12.5%) 4/45 (8.89%) Yasliani et al. 2009 Iran 200 160 22 Urine, Blood, Stool, Wound Disk diffusion 17 5/160 (3.13%) 8/22 (36.36%) Zhao et al. 2019 China 110 35 44 Bile VTEK 2 1 1/35 (2.86%) 0 3.2 The pooled prevalence of VRE Based on 39 studies, the pooled prevalence of VRE in Asia was 8.10% (95% CI- 0.07–0.09). However, there was severe heterogeneity (I2 = 93.79%, T2 = 0.00, p = 0.00) and the prevalence rate ranged from 1% to 27.70%. (Figure 2). FIGURE 2Open in figure viewerPowerPoint Forest plot showing the estimated pooled prevalence of VRE in Asia 3.3 Sensitivity analysis and subgroup analysis There was no significant change in the degree of heterogeneity when studies were omitted one by one in the analysis (Appendix S3). The degree of heterogeneity was between 93.01% and 93.95%. All these studies were included in the meta-analysis. The subgroup analysis was done using the study area (Five Asia regions-East Asia, Central Asia, South Asia, South East Asia and Western Asia), detection method, study period and species isolated (E. faecalis and E. faecium). (Table 2). TABLE 2. Subgroup analysis by regions of Asia, detection method, time period and enterococcal species isolated Number of studies Number of enterococci isolated, N VRE number Pooled prevalence (95% CI) Heterogeneity (I2) p-value Asian regions South Asia (India, Pakistan) 14 4907 332 7.70% (0.054–0.100) 92.22% <0.001 Southeast Asia (Malaysia) 2 807 13 1.80% (−0.002–0.038) 65.78% <0.001 Western Asia (Iran, Saudi Arabia, Jordan, Kuwait) 18 4284 473 11.40% (0.0843–0.143) 92.64% <0.001 East Asia (China) 5 1877 75 3.10% (0.006–0.057) 92.04% <0.001 Detection method Disk diffusion 23 8254 606 8.70% (0.068–0.105) 95.01% <0.001 Agar dilution 6 1107 74 6.70% (0.032–0.101) 84.61% <0.001 E test 8 1887 158 8.30% (0.047–0.118) 91.76% <0.001 Broth dilution 1 517 54 – – – VTEK 2 1 110 1 – – – Study period 2000–2010 12 3801 257 6.40% (0.040–0.087) 92% <0.001 2010–2020 27 8074 636 9.10% (0.072–0.109) 94.49% <0.001 Species isolated Enterococci faecalis 27 5198 234 3.70% (0.027–0.047) 72.83% <0.001 E. faecium 28 2259 474 22.40% (0.184–0.305) 95.66% <0.001 Subgroup analysis by regions of Asia revealed the highest prevalence of VRE in Western Asia (Pooled Prevalence—11.40%), followed by South Asia (7.70%). The least VRE prevalence was seen in South-East Asia (1.80%) and East Asia (3.10%). No studies of central Asia qualified for the review. The majority of the included studies used the disk diffusion method (n = 25) as the antibiotic susceptibility test for the detection of resistant enterococci. It resulted in a pooled prevalence of 8.70%. Also, E test and Agar dilution methods showed a prevalence of 6.70% and 8.30% respectively. The pooled prevalence of VRE using various methods of detection showed similar results. Twelve studies published before 2010 and 27 of the 39 studies published after 2010 showed a slightly increasing trend of VRE prevalence in Asia with a pooled prevalence of 6.40% and 9.10%, respectively. 3.4 Heterogeneity analysis In this meta-analysis, we observed a severe heterogeneity (I2 = 93.79%, T2 = 0.00, p = 0.00) between the studies. Subgroup analysis also revealed a high level of heterogeneity (I2 = 65.78%–95.60%). Meta-regression was used to indicate the source of heterogeneity using the Asian region, detection methods and study period as covariates. The meta-regression analysis showed that the two covariates, (detection method and study periods) were not statistically significant while the covariate Asian region was statistically significant for the presence of heterogeneity. (Table 3). TABLE 3. Meta-regression analysis of covariates with the heterogeneity of prevalence of VRE in Asian countries Heterogeneity source Coefficients Standard error [95% CI] p-value Asian regions −0.0204433 0.0061451 −0.0324874 −0.0083991 0.001 Detection method −0.0077606 0.0069088 −0.0213016 0.0057804 0.261 Study period 0.0260099 0.0159825 −0.0053152 0.0573349 0.104 3.5 Publication bias Although the funnel plot of standard error and effect size could not give a clear indication of publication bias, the linear regression test for small study effect size confirmed no publication bias in all the 39 studies reporting the prevalence of VRE (Egger's test: p = 0.509). (Figure 3). FIGURE 3Open in figure viewerPowerPoint Funnel Plot of standard error and effect sizes visualizing 39 studies 4 DISCUSSION The overall estimate of the prevalence of VRE in Asia was 8.10% among 11,875 enterococcal isolates. It is closer to the prevalence of 11.9%, reported by a surveillance study among 4018 Enterococci species in the Asia Pacific region and lower than the reported prevalence of 23% by a meta-analysis among the patients with malignancy in Asia.22, 23 Our finding was higher than the prevalence reported in the studies from Spain (0.7%),24 France (1.0%),25 Europe (4.0%)26 and Canada (6.0%)27 whereas lower than that of the United States (35.5%).28 North America (21%),23 Belgium (12.8%),29 Germany (9.8%) and30 the United Kingdom (9.2%).31 Underlying diseases, previous hospitalization, contact with VRE patients, urinary catheter, severe illness, prolonged hospital stay, inappropriate use of antimicrobials, oral vancomycin use, the practice of high frequency of empirical therapies and poor knowledge, attitude and practice about infection control among health care workers were identified as the risk factors for acquiring VRE infections.32-34 Apart from humans, many mammals and birds are also reservoirs of enterococci. Inappropriate use of antibiotics among livestock is contributing to the emergence of VRE. A study reported a high prevalence of MDR enterococci including VRE in the faeces of livestock, environmental water and sewage.35 Transmission of microorganisms to humans through animal food as well as the feco-oral route through contaminated water and food could be one of the reasons for increasing VRE prevalence in Asia, especially South and South-east Asian region.35 The prevalence of resistance to vancomycin among E. faecium isolates was higher than that of E. faecalis isolates (22.40% vs. 3.70%). This finding is consistent with the finding of worldwide surveillance.22 Although E. faecalis has a greater role in infections due to proliferation in the intestine, E. faecium has high potential in the attainment of resistance materials making this strain extremely resistant to numerous antimicrobials.36, 37 E. faecium is increasingly being reported as the leading species among VRE which is attributed to one of the eight phenotypic variants of glycopeptide resistance, VanA, which is mostly carried by E. faecium.38 Our review showed that the pooled prevalence of VRE from 2000 to 2010 was 6.40% which has increased to 9.10% in the years 2010 to 2020, but time period was not a significant predictor for VRE prevalence (p = 0.104) with a small absolute difference. This increasing trend may be partly explained by the rising number of diagnoses of infections and colonization with VRE, increased screening efforts and bigger consumption of vancomycin leading to its resistance among enterococci, but may also due to random alterations between studies. A rising number of infections with VRE have also been reported from Australia, Canada and Switzerland.39-41 Inappropriate use of antimicrobials and poor antimicrobial usage policies particularly vancomycin for the enterococcal infection treatment could also explain this increasing trend. The regional prevalence of VRE was also assessed. Vancomycin resistance tended to be higher in Western Asian locations (11.40%) followed by South Asian locations (7.70%), East Asia (3.10%) and the lowest in South-east Asia (1.80%). This variation might be due to diverse study settings, sample population, study period, the disparity in antimicrobial use and detection method of antimicrobial susceptibility. Further, poor sanitation, faulty health control management and insufficient antibiotic supervision programmes in the Western Asian region could be the reasons for the highest level of vancomycin resistance seen in this region.42 The second highest prevalence of VRE was found in the South Asian region, which includes the countries that are the main importer of livestock. Unwarranted use of antimicrobials in the livestock leading to a high prevalence of MDR enterococci species including VRE, might have resulted in their spread, which could get transmitted to humans through the consumption of various livestock in these countries.43, 44 Low prevalence was seen in the East Asian region could be because of low occurrence and distribution of VRE in the livestock and hospitals of this region, the use of lower dosage of vancomycin clinically and relatively high investment in the healthcare resources.45-47 In South-east Asia there were two studies reporting a total of only 807 enterococcal isolates of which number of VRE was 13, all the three parameters being lowest when compared to other regions. Very few reports on the isolation of VRE in the South-east Asian region might have resulted in the lowest prevalence among other regions in Asia. The disk diffusion method was the main method for antibiotic susceptibility tests and was interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guideline. Additionally, agar dilution and E test were also used. Twenty-five studies used the disk diffusion method for antibiotic susceptibility test while eight used the E test, five used agar dilution, and one study used the broth dilution method and VTEK2 each. Subgroup analysis of VRE prevalence according to detection methods showed similar results in our study. Urine, blood, stool and body fluids were the commonest specimens from which VRE was isolated. This is in line with the studies reporting the urinary tract, bloodstream and intestinal tract as the commonest specimen for VRE isolation.48-50 4.1 Strength/Limitations A comprehensive search with clear inclusion and exclusion criteria was used, examined common clinical specimens and standard methods of antibiotic susceptibility testing. Our study investigates the prevalence of vancomycin resistance in two common enterococci species isolated from various samples across different parts of Asia. There were a number of limitations in-depth and breadth of data. The unpublished and case-control studies were not included. Data were not available from all the Asian countries. Outside health care settings and studies reporting VRE from non-human sources were excluded which could potentially underestimate the actual VRE prevalence. As mentioned, some enterococci species, namely E. gallinarum and E. casseliflavus are intrinsically resistant to vancomycin which have been
Publication Year: 2021
Publication Date: 2021-02-25
Language: en
Type: review
Indexed In: ['crossref', 'pubmed']
Access and Citation
Cited By Count: 27
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