Abstract
Background
Gram-positive bacteria are dangerous and challenging agents of infection due to their increasing resistance to antibiotics. We aim to analyse the epidemiology and risk factors of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) in Zhejiang China.
Methods
Gram-positive bacteria (including S. aureus, Enterococcus faecalis and Enterococcus faecium) were collected from eighty-six hospitals of eleven cities in Zhejiang China from 2015 to 2017. The detection rates of MRSA and VRE infection were calculated for the non-duplicated isolate according to year, region, hospital level, patient age, specimen type and patient category. Meanwhile, the detected resistances of MRSA, E. faecalis and E. faecium to different antibiotics from 2015 to 2017 were compared. The risk factors and the differences in MRSA and VRE detection rates were compared using odds ratio (OR) with 95% confidence interval (95% CI) and Chi-square test respectively.
Results
From 2015 to 2017, the detection rates of MRSA and VRE decreased gradually. The cities with the highest MRSA and VRE detection rates tended to be adjacent; for example, the neighbouring cities Hangzhou and Quzhou had simultaneously high rates of MRSA and VRE infection. Patients from IIIA hospital who were older than 75 years and in the intensive care unit (ICU) were most at risk. No vancomycin-resistant isolate was found in MRSA. Resistance of E. faecalis and E. faecium to vancomycin and linezolid decreased slightly and then maintained a low level.
Conclusions
The detection rates of MRSA and VRE stayed at moderate and low levels during the three year period of this study, while local dissemination was found in MRSA and VRE isolates. Sustained surveillance is necessary to prevent the spread or clonal dissemination of drug-resistant strains in Zhejiang China.
Similar content being viewed by others
Background
Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium are dangerous and challenging agents of infection due to their increasing resistance to antibiotics [1]. Among these, S. aureus are the most frequently isolated, making up 29.1% of the isolated Gram-positive bacterial populations, and infections caused by S. aureus (both community-associated or nosocomial-associated) are reported all over the world [2, 3]. Enterococci (including E. faecalis and E. faecium) are the second frequently isolated Gram-positive bacteria at 19.5%. Past generations of enterococci were mainly associated to urinary-tract infection, but recently more and more enterococci are isolated from other infections [4], and an outbreak of vancomycin resistant enterococci (VRE) in a solid organ transplant unit was reported in 2018 [5].
The epidemiology of resistance in Gram-positive bacteria has undergone major changes in recent decades, with methicillin-resistant S. aureus (MRSA) and VRE now being of international concern [6]. Antimicrobial resistances of Gram-positive bacteria have been reported in many countries [7,8,9]; however, it was only in recent years that vanM-carrying E. faecalis strains were isolated from patients and the clinical environment in the Second Affiliated Hospital of Zhejiang University School of Medicine [27]. These may have a different resistance than strains with the vanM gene, seen in China [28] or in strains with vanA dominance, seen in Poland [29]. In our study, resistance rate of E. faecalis to linezolid increased from 1.6% in 2008 to 2.97% in 2016 [36] and can be attributed to patients with severe co-morbidities. Stratifying the data by patient age, it is observed that the proportion of MRSA and VRE was the highest in isolates from elderly patients older than 75 years, but was the lowest from children aged 2 years - 3 years and infants younger than 1 year. The high numbers of MRSA and VRE isolates from elderly patients may be due to these patients having more underlying diseases and a greater history of antibiotic use than the child and the infant group. As well, decreased nutrition and immune function, often seen in the elderly, may also be contributing elements. Other identified risk factors associated with MRSA and VRE include having a source of isolates. We found that puncture fluid (containing hydrothorax, ascites, articular cavity fluid, pericardial fluid and cerebrospinal fluid) has the lowest proportion (21.32%) of MRSA, though the underlying reason for this phenomenon needs to be further studied. In terms of treatment, we should be wary of methicillin-sensitive S. aureus when S. aureus is isolated from puncture fluid in Zhejiang province. With the noted exception of blood and urine, there is no difference in the specimen types in proportions of VRE isolates.
These findings will provide valuable information for infection control practices. Although many surveillance projects of antibiotic resistance have been carried out in China, they always cover only the tertiary hospitals. In our study, a wider range of scenarios were seen where resistant strains could occur, indicating the importance of performing regional antibiotic resistance surveillance. The current study had some limitations: we had a relatively short span of time (3 years) for the data collection, we had a limited number of IIB hospitals to contribute data to the study, and because ours was a retrospective analysis, we had an inability to obtain the original strains. In the future, we would like to expand this surveillance to cover more IIB and rural area clinics and also collect the original strains for intensive study.
Conclusion
The detection rates of MRSA stayed at moderate levels, and VRE stayed at low levels during the last three years, and local dissemination was found in MRSA and VRE isolates. The highest risk factors for MRSA and VRE infection were patient status in a IIIA hospital, age older than 75 years and hospitalization in the ICU ward. As a result of our findings, we suggest that sustained surveillance is necessary to prevent the spread or clonal dissemination of drug-resistant strains in Zhejiang China.
Abbreviations
- CI:
-
Confidence interval
- ICU:
-
Intensive care unit
- MALDI-TOF-MS:
-
Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry
- MIC:
-
Minimum inhibitory concentration
- MRSA:
-
Methicillin-resistant Staphylococcus aureus
- OR:
-
Odds ratio
- VRE:
-
Vancomycin-resistant enterococci
References
Bereket W, Hemalatha K, Getenet B, Wondwossen T, Solomon A, Zeynudin A, Kannan S. Update on bacterial nosocomial infections. Eur Rev Med Pharmacol Sci. 2012;16:1039–44.
Sacar S, Sayin KS, Turgut H, Cevahir N, Hircin Cenger D, Tekin K. Epidemiology and associated factors for nosocomial methicillin-resistant Staphylococcus aureus infection in a tertiary-care hospital. Epidemiol Infect. 2010;138(5):697–701.
DeLeo FR, Otto M, Kreiswirth BN, Chambers HF. Community-associated meticillin-resistant Staphylococcus aureus. Lancet. 2010;375:1557–68.
Uçkay I, Pires D, Agostinho A, Guanziroli N, Öztürk M, Bartolone P, Tscholl P, Betz M, Pittet D. Enterococci in orthopaedic infections: Who is at risk getting infected? Journal of Infection. 2017;75(4):309-14.
Peter K, Astrid M, Guido H, Michael B, Ludwig K, Stefan F, Wilfried P, Stephan E, Alois O, Lass-Flörl C, et al. Outbreak report: a nosocomial outbreak of vancomycin resistant enterococci in a solid organ transplant unit. Antimicrob Resist Infect Control. 2018;7(1):86.
Rupp ME, Fitzgerald T, Hayes K, Van ST, Hewlett A, Clevenger R, Lyden E. Effect of cessation of contact isolation for endemic methicillin-resistant Staphylococcus aureus and Vancomycin-resistant Enterococci. Infect Control Hosp Epidemiol. 2017;38(8):1–3.
Ramirez MJY, Nick D, Elias MN, Amuah JE, Kathryn B, Couris CM, Kira L. A comparison of administrative data versus surveillance data for hospital-associated methicillin-resistant Staphylococcus aureus infections in Canadian hospitals. Infect Control Hosp Epidemiol. 2017;38(4):436–43.
Watson S, Cabrera‐Aguas M, Khoo P, Pratama R, Gatus BJ, Gulholm T, El‐Nasser J, Lahra MM. Keratitis antimicrobial resistance surveillance program, Sydney, Australia: 2016 Annual Report. Clin Exp Ophthalmol. 2019;47(1):20-5.
Seas C, Garcia C, Salles MJ, Labarca J, Luna C, Alvarez-Moreno C, Mejía-Villatoro C, Zurita J, Guzmán-Blanco M, Rodríguez-Noriega E, et al. Staphylococcus aureus bloodstream infections in Latin America: results of a multinational prospective cohort study. J Antimicrob Chemother. 2018;73(1).
Zhang GS, Lin XH, Cai JC, Zhang R, **u HQ, Tian BP, Cui W. Characteristics of clinical and environmental, vanM-carrying vancomycin-resistant enterococci isolates from an infected patient. Int J Antimicrob Agents. 2018:S0924857918300062.
Zhao C, Sun H, Wang H, Liu Y, Hu B, Yu Y, Sun ZY, Chu YZ, Cao B, Liao K, et al. Antimicrobial resistance trends among 5608 clinical gram-positive isolates in China: results from the gram-positive Cocci resistance surveillance program (2005-2010). Diagn Microbiol Infect Dis. 2012;73(2):174–81.
Sun HL, Wang H, Chen MJ, Liu YM, Hu ZD, Liao K, Chu YZ, Lei JE, Zhang B, Yu YS, et al. An antimicrobial resistance surveillance of gram-positive cocci isolated from 12 teaching hospitals in China in 2009. Chin J Lab Med. 2006;49(9):735.
Jorgensen JH. Manual of clinical microbiology, 11th edition [J]; 2015.
Patel JB, Cockerill Iii FR, Alder J. Performance standards for antimicrobial susceptibility testing; twenty-fourth InformationalSupplement. Clinical and laboratory standards institute antimicrobial susceptibility testing M100-S24, vol. 34; 2014. p. 1–230.
Decousser JW, Woerther PL, Soussy CJ, Marguerite FG, Dowzicky MJ. The tigecycline evaluation and surveillance trial; assessment of the activity of tigecycline and other selected antibiotics against gram-positive and gram-negative pathogens from France collected between 2004 and 2016. Antimicrob Resist Infect Control. 2018;7(1):68.
European Centre for Disease Prevention and Control. Surveillance of antimicrobial resistance in Europe 2016. Annual report of the European antimicrobial resistance network (EARS-net). Stockholm: ECDC; 2017.
Shibl AM, Memish ZA, Kambal AM, Ohaly YA, Ishaq A, Senok AC, Livermore DM. National surveillance of antimicrobial resistance among gram-positive bacteria in Saudi Arabia. J Chemother. 2014;26(1):13–8.
Marco F, Dowzicky MJ. Antimicrobial susceptibility among important pathogens collected as part of the Tigecycline evaluation and surveillance trial (T. E.S.T.) in Spain, 2004–2014. J Glob Antimicrob Resist. 2016;6:50–6.
Kehrmann J, Kaase M, Szabados F, Gatermann SG, Buer J, Rath PM, Steinmann J. Vancomycin MIC creep in MRSA blood culture isolates from Germany: a regional problem? Eur J Clin Microbiol Infect Dis. 2011;30(5):677–83.
**e XY, Yu YS. Zhejiang provincial hospital bacterial resistance testing yearbook. 2015. Zhejiang University Press; 2015.
**e XY, Yu YS. Zhejiang provincial hospital bacterial resistance testing yearbook. 2017. Zhejiang University Press; 2017.
Yang XJ, Chen Y, Yang Q, Qu TT, Liu LL, Wang HP, Yu YS. Emergence of cfr-harbouring coagulase-negative staphylococci among patients receiving linezolid therapy in two hospitals in China. J Med Microbiol. 2013;62:845–50.
Cui L, Wang Y, Li Y, He T, Schwarz S, Ding Y, Shen J, Lv Y. Cfr-mediated linezolid-resistance among methicillin-resistant coagulase negative staphylococci from infections of humans. PLoS One. 2013;8(2):e57096.
Cai JC, Hu YY, Zhou HW, Chen GX, Zhang R. Dissemination of the same cfr-carrying plasmid among methicillin-resistant staphylococcus aureus and coagulase-negative staphylococcal isolates in China. Antimicrob Agents Chemother. 2015;59(6):3669–71.
Gudiol C, Ayats J, Camoez M, Domínguez MA, García-Vidal C, Bodro M, Ardanuy C, Obed M, Arnan M, Antonio M, et al. Increase in bloodstream infection due to Vancomycin-susceptible Enterococcus faecium in Cancer patients: risk factors, molecular epidemiology and outcomes. PLoS One. 2013;8(9):e74734.
Morris-Downes M, Smyth EG, Moore J, Thomas T, Fitzpatrick F, Walsh J, Caffreyc V, Morrisc A, Foleye S, Humphreys H. Surveillance and endemic vancomycin-resistant enterococci: some success in control is possible. J Hosp Infect. 2010;75(3):228–33.
Zhou X, Arends JP, Kam**a GA, et al. Evaluation of the Xpert vanA/vanB assay using enriched inoculated broths for direct detection of vanB vancomycin-resistant Enterococci.[J]. J Clin Microbiol. 2014;52(12):4293.
Chen CH, Sun JY, Guo Y, Lin DF, Guo QL, Hu FP, Zhu DM, Xu XG, Wang MG. High prevalence of vanM in vancomycin-resistant Enterococcus faecium isolates from Shanghai, China. Antimicrob Agents Chemother. 2015;59(12):7795–8.
Wardal E, Kuch A, Gawryszewska I, Żabicka D, Hryniewicz W, Sadowy E. Diversity of plasmids and Tn 1546 -type transposons among VanA Enterococcus faecium, in Poland. Eur J Clin Microbiol Infect Dis. 2017;36(2):313–28.
Arias CA, Murray BE. Emergence and management of drug-resistant enterococcal infections. Expert Rev Anti-Infect Ther. 2008;6:637–55.
Diaz L, Kiratisin P, Mendes RE, Panesso D, Singh KV, Arias CA. Transferable plasmid-mediated resistance to linezolid due to cfr in a human clinical isolate of Enterococcus faecalis. Antimicrob Agents Chemother. 2012;56(7):3917–22.
Zhang YZ, Dong GF, Li YH, Chen LJ, Liu HY, Bi WZ, Lu H, Zhou TL. A high incidence and coexistence of multiresistance genes cfr and optrA among linezolid-resistant enterococci isolated from a teaching hospital in Wenzhou, China. Eur J Clin Microbiol Infect Dis. 2018;37(8):1441–8.
Lazaris A, Coleman DC, Kearns AM, Pichon B, Kinnevey PM, Earls MR, Boyle B, O'Connell B, Brennan GI, Shore AC. Novel multiresistance cfr plasmids in linezolid-resistant methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium (VRE) from a hospital outbreak: co-location of cfr and optrA in VRE. J Antimicrob Chemother. 2017;72(12):3252–7.
Wang Y, Lv Y, Cai JC, Schwarz S, Cui L, Hu Z, Zhang R, Li J, Zhao Q, He T, et al. A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of human and animal origin. J Antimicrob Chemother. 2015;70(8):2182–90.
Upreti N, Rayamajhee B, Sherchan SP, Choudhari MK, Banjara MR. Prevalence of methicillin resistant Staphylococcus aureus, multidrug resistant and extended spectrum β-lactamase producing gram negative bacilli causing wound infections at a tertiary care hospital of Nepal. Antimicrob Resist Infect Control. 2018;7(1).
Zhou XW, Garcia-Cobos S, Ruijs GJHM, Greetje A, Kam**a AJP, Bors DM, Moller LV. Epidemiology of extended-Spectrum beta-lactamase-producing E-coli and Vancomycin-resistant Enterococci in the northern Dutch-German cross-border region. Front Microbiol. 2017;8.
Acknowledgements
We want to thank the participating hospitals for their work and cooperation. We also want to thank the drug resistance monitoring group of the Zhejiang Province.
Funding
This study was supported by grants from the National Natural Science Foundation of China (No. 81871705 from Gongxiang Chen).
Availability of data and materials
All data generated or analysed during this study are included in this manuscript.
Author information
Authors and Affiliations
Contributions
HL, CJM, LHY, CS, DSB and ZR contributed to the acquisition and analysis of the data. HL wrote the initial draft of this paper. HYY and ZHW performed the statistical analyses. CGX contributed to the concept of the study, the revision of this paper, and the final approval of the version to be published. All authors have read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Not applicable
Consent for publication
Not applicable
Competing interests
The authors declare that they have no competing interests.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
About this article
Cite this article
Huang, L., Zhang, R., Hu, Y. et al. Epidemiology and risk factors of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci infections in Zhejiang China from 2015 to 2017. Antimicrob Resist Infect Control 8, 90 (2019). https://doi.org/10.1186/s13756-019-0539-x
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s13756-019-0539-x