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Recent advances in the detection of methicillin resistant Staphylococcus aureus (MRSA)

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Abstract

According to the World Health Organization (WHO) 20% of all documented S. aureus infections are attributable to MRSA, although for some developing countries this value can exceed 80%. Thus the rapid and accurate detection of MRSA in low resource settings (LDR) is becoming essential. Yet conventional microbial detection methods take from 1-5 days to identify MRSA. Recently, new types of automated laboratory methods as well as advances in nucleic acid testing, microfluidic technology, immunosensors, biosensors and point of care testing have reduced the time to detection to <1 hr. This review examines the current limitations and advances in methodologies employed in the rapid detection of MRSA.

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References

  1. Malhotra-Kumar, S. et al. Current trends in rapid diagnostics for methicillin-resistant Staphylococcus aureus and glycopeptide-resistant enterococcus species. J. Clin. Microbiol. 46, 1577–1587 (2008).

    Article  Google Scholar 

  2. Koydemir, H.C. et al. MEMS biosensors for detection of methicillin resistant Staphylococcus aureus. Biosens. Bioelectron. 29, 1–12 (2011).

    Article  Google Scholar 

  3. Tübbicke, A., Hübner, C., Kramer, A., Hübner, N.O. & Fleßa, S. Transmission rates, screening methods and costs of MRSA -a systematic literature review related to the prevalence in Germany. Eur. J. Clin. Microbiol. Infect. Dis. 31, 2497–2511 (2012).

    Article  Google Scholar 

  4. Nonhoff, C., Roisin, S., Hallin, M. & Denis, O. Evaluation of Clearview Exact PBP2a, a New Immunochromatographic Assay, for Detection of Low-Level Methicillin-Resistant Staphylococcus aureus (LL-MRSA). J. Clin. Microbiol. 50, 3359–3360 (2012).

    Article  Google Scholar 

  5. Kong, H., Tong, L., Zhang, W., Fu, Y. & Li, X. Combined use of the BinaxNOW Staphylococcus aureus test with the Clearview PBP2a assay for the early detection of methicillin-resistant S. aureus from positive blood cultures. Diagn. Microbiol. Infect. Dis. 78, 226–228 (2014).

    Article  CAS  Google Scholar 

  6. Mantiona, B., Cavaliéa, L. & Prére, M.F. Evaluation of an immunochromatographic assay for detection of PBP2a on non-Staphylococcus aureus clinical isolates. J. Microbiol. Methods. 112, 46–48 (2015).

    Article  Google Scholar 

  7. Dupieux, C. et al. Evaluation of a commercial immunochromatographic assay for rapid routine identification of PBP2a-positive Staphylococcus aureus and coagulase-negative staphylococci. Diagn. Microbiol. Infect. Dis. 86, 262–264 (2016).

    Article  CAS  Google Scholar 

  8. Baba, T. et al. Complete genome sequence of Macrococcus caseolyticus strain JCSCS5402, [corrected] reflecting the ancestral genome of the human-pathogenic staphylococci. J. Bacteriol. 191, 1180–1190 (2009).

    Article  CAS  Google Scholar 

  9. Garcia-Alvarez, L. et al. Methicillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study. Lancet. Infect. Dis. 11, 595e603 (2011).

    Google Scholar 

  10. Harrison, E.M. et al. A novel hybrid SCCmec-mecC region in Staphylococcus sciuri. J. Antimicrob. Chemother. 69, 911e8 (2014).

    Google Scholar 

  11. Hiramatsu, K. et al. Vancomycin-intermediate resistance in Staphylococcus aureus. J. Glob. Antimicrob. Resist. 2, 213–224 (2014).

    Article  Google Scholar 

  12. Harbarth, S. et al. Update on screening and clinical diagnosis of methicillin-resistant Staphylococcus aureus (MRSA). Int. J. Antimicrob. Agents. 37, 110–117 (2011).

    Article  CAS  Google Scholar 

  13. Dunne, W.M., Westblade, L.F. & Ford, B. Next-generation and whole-genome sequencing in the diagnostic clinical microbiology laboratory. Eur. J. Clin. Microbiol. Infect. Dis. 31, 1719–1726 (2012).

    Article  CAS  Google Scholar 

  14. Toleman, M.S. et al. Systematic Surveillance Detects Multiple Silent Introductions and Household Transmission of Methicillin-Resistant Staphylococcus aureus USA300 in the East of England. J. Infect. Dis. 214, 447–453 (2016).

    Article  Google Scholar 

  15. Gardete, S. & Tomasz, A. Mechanisms of vancomycin resistance in Staphylococcus aureus. J. Clin. Invest. 124, 2836–2840 (2014).

    Article  CAS  Google Scholar 

  16. Hiramatsu, K. et al. Multi-drug-resistant Staphylococcus aureus and future chemotherapy. J. Infect. Chemother. 20, 593e601 (2014).

    Article  Google Scholar 

  17. te Witt, R., van Belkum, A. & van Leeuwen, W.B. Molecular diagnostics and genotyping of MRSA: an update. Expert. Rev. Mol. Diagn. 10, 375–380 (2010).

    Article  Google Scholar 

  18. Vandenesch, F. et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg. Infect. Dis. 9, 978–984 (2003).

    Article  Google Scholar 

  19. Park, K.H. et al. Community-associated MRSA strain ST72-SCCmecIV causing bloodstream infections: clinical outcomes and bacterial virulence. J. Antimicrob. Chemother. 70, 1185–1192 (2015).

    CAS  Google Scholar 

  20. Peng, Y. et al. Metro system in Guangzhou as a hazardous reservoir of methicillin resistant Staphylococci: findings from a point-prevalence molecular epidemiologic study. Sci. Rep. 5, 16087 (2015).

    Article  CAS  Google Scholar 

  21. Klevens, R.M. et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298, 1763–1771 (2007).

    Article  CAS  Google Scholar 

  22. Wang, J. et al. Morin hydrate attenuates Staphylococcus aureus virulence by inhibiting the self-assembly of α-hemolysin. J. Appl. Microbiol. 118, 1365–2672 (2015).

    Google Scholar 

  23. Otto, M. Staphylococcus aureus toxins. Curr. Opin. Microbiol. 17, 32–37 (2014).

    Article  CAS  Google Scholar 

  24. Kim, E.S. et al. Clinical and Epidemiological Factors Associated with Methicillin Resistance in Community-Onset Invasive Staphylococcus aureus Infections: Prospective Multicenter Cross-Sectional Study in Korea. PLoS One 9, e114127 (2014).

    Article  Google Scholar 

  25. Buchan, B.W. & Ledeboer, N.A. Emerging Technologies for the Clinical Microbiology Laboratory. Clin. Microbiol. Rev. 27, 783–822 (2014).

    Article  CAS  Google Scholar 

  26. Cohen, J. et al. Sepsis: a roadmap for future research. Lancet. Infect. Dis. 15, 581–614 (2015).

    Article  Google Scholar 

  27. Bassetti, M. et al. Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria. Intensive. Care. Med. 41, 776–795 (2015).

    Article  CAS  Google Scholar 

  28. Hager, J. Making and using spotted DNA microarrays in an academic core laboratory. Meth. Enzymol. 410, 135–168 (2006).

    Article  CAS  Google Scholar 

  29. Strauss, C., Endimiani, A. & Perreten, V. A novel universal DNA labeling and amplification system for rapid microarray-based detection of 117 antibiotic resistance genes in Gram-positive bacteria. J. Microbiol. Methods 108, 25–30 (2015).

    Article  CAS  Google Scholar 

  30. Miller, M.B. & Tang, Y.W. Basic concepts of microarrays and potential applications clinical microbiology. Clin. Microbiol. Rev. 22, 611–633 (2009).

    Article  CAS  Google Scholar 

  31. Hwang, K.Y. et al. Solid phase DNA extraction with a flexible bead-packed microfluidic device to detect methicillin-resistant Staphylococcus aureus in nasal swabs. Anal. Chem. 84, 7912–7918 (2012).

    Article  CAS  Google Scholar 

  32. Reuter, S. et al. Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland. Genome. Res. 26, 263–270 (2016).

    Article  CAS  Google Scholar 

  33. Fleurbaaij, F. et al. Capillary-Electrophoresis Mass Spectrometry for the Detection of Carbapenemases in (Multi-) Drug-Resistant Gram-Negative Bacteria. Anal. Chem. 86, 9154–9161 (2014).

    Article  CAS  Google Scholar 

  34. Rees, J.C., Pierce, C.L., Schieltz, D.M. & Barr, J.R. Simultaneous Identification and Susceptibility Determination to Multiple Antibiotics of Staphylococcus aureus by Bacteriophage Amplification Detection Combined with Mass Spectrometry. Anal. Chem. 87, 6769–6777 (2015).

    Article  CAS  Google Scholar 

  35. Aros-Calt, S. et al. Annotation of the Staphylococcus aureus Metabolome Using Liquid Chromatography Coupled to High-Resolution Mass Spectrometry and Application to the Study of Methicillin Resistance. J. Proteome. Res. 14, 4863–4875 (2015).

    Article  CAS  Google Scholar 

  36. Wang, T. et al. Determining Carbapenemase Activity with 18O Labeling and Targeted Mass Spectrometry. Anal. Chem. 85, 11014–11019 (2013).

    Article  CAS  Google Scholar 

  37. Chudobova, D. et al. 3D-printed chip for detection of methicillin-resistant Staphylococcus aureus labeled with gold nanoparticles. Electrophoresis 36, 457–466 (2015).

    Article  CAS  Google Scholar 

  38. Yuen, J.W.M., Chung, T.W.K & Loke, A.Y. Methicillin-Resistant Staphylococcus aureus (MRSA) Contamination in Bedside Surfaces of a Hospital Ward and the Potential Effectiveness of Enhanced Disinfection with an Antimicrobial Polymer Surfactant. Int. J. Environ. Res. Publ. Health. 12, 3026–3041 (2015).

    Article  CAS  Google Scholar 

  39. Silbert, S., Kubasek, C., Uy, D. & Widen, R. Comparison of ESwab with Traditional Swabs for Detection of Methicillin-Resistant Staphylococcus aureus Using Two Different Walk-Away Commercial Real-Time PCR Methods. J. Clin. Microbiol. 52, 2641–2643 (2014).

    Article  Google Scholar 

  40. Hombach, H., Maurer, F.P., Pfiffner, T., Böttger, E.C. & Furrer, R. Standardization of Operator-Dependent Variables Affecting Precision and Accuracy of the Disk Diffusion Method for Antibiotic Susceptibility Test. J. Clin. Microbiol. 53, 3864–3869 (2015).

    Article  Google Scholar 

  41. Shin, J.H. et al. A Multicentre Study about Pattern and Organisms Isolated in Follow-up Blood Cultures. Ann. Clin. Microbiol. 16, 8–12 (2013).

    Article  Google Scholar 

  42. Robotham, J.V. et al. Screening, isolation, and de-colonisation strategies in the control of methicillin resistant Staphylococcus aureus in intensive care units: cost effectiveness evaluation. BMJ 343, d5694 (2011).

    Article  Google Scholar 

  43. Stürenburg, E. Rapid detection of methicillin-resistant Staphylococcus aureus directly from clinical samples: methods, effectiveness and cost considerations. Ger. Med. Sci. 7, Doc06 (2009).

    Google Scholar 

  44. Matsui, H. et al. Development of an Immunochromatographic Strip for Simple Dtection of Penicillin-Binding Protein 2a. Clin. Vaccine Immunol. 18, 248–253 (2011).

    Article  CAS  Google Scholar 

  45. Liu, Y. et al. Development of an immunoaffinity solid phase microextraction method for the identification of pencillin binding protein 2a. J. Chromatogr. A. 1364, 64–73 (2014).

    Article  CAS  Google Scholar 

  46. Kumar, S.M. et al. Current Trends in Rapid Diagnostics for Methicillin-Resistant Staphylococcus aureus and Glycopeptide-Resistant Enterococcus Species. J. Clin. Microbiol. 46, 1577–1587 (2008).

    Article  Google Scholar 

  47. Ellem, J.A., Olma, T. & O’Sullivan, M.V.N. Rapid Detection of Methicillin-Resistant Staphylococcus aureus and Methicillin-Susceptible S. aureus Directly from Positive Blood Cultures by Use of the BD Max Staph SR Assay. J. Clin. Microbiol. 53, 3900–3904 (2015).

    Article  CAS  Google Scholar 

  48. Warnke, P., Frickmann, H., Ottl, P. & Podbielski, A. Nasal Screening for MRSA: Different Swabs -Different Results. PLoS One 9, e111627 (2014).

    Article  Google Scholar 

  49. Holtfreter, S. et al. Molecular epidemiology of Staphylococcus aureus in the general population in Northeast Germany-results of the Study of Health in Pomerania (SHIP-TREND-0). J. Clin. Microbiol. 54, doi: 10.1128/JCM.00312-16 (2016).

    Google Scholar 

  50. Faron, M.L. et al. Automated Scoring of Chromogenic Media for the Detection of MRSA Using the WASPLab Image Analysis Software. J. Clin. Microbiol. 54, 620–624 (2016).

    Article  CAS  Google Scholar 

  51. Rajendran, R. & Rayman, G. Point-of-Care Blood Glucose Testing for Diabetes Care in Hospitalized Patients: An Evidence-Based Review. J. Diabetes. Sci. Technol. 8, 1081–1090 (2014).

    Article  Google Scholar 

  52. Warnke, P. et al. Utilizing Moist or Dry Swabs for the Sampling of Nasal MRSA Carriers? An In Vivo and In Vitro Study. PLoS One 11, e0163073 (2016).

    Article  Google Scholar 

  53. Pinchuk, I.V. et al. Staphyloccocus enterotoxins. Toxins. 2, 2177–2197 (2010).

    Article  CAS  Google Scholar 

  54. Templeman, L.A. et al. Quantitating staphylococcal enterotoxin B in diverse media using a portable fiber-optic biosensor. Anal. Biochem. 233, 50–57 (1996).

    Article  Google Scholar 

  55. Goldman, E.R. et al. Conjugation of luminescent quantum dots with antibodies using an engineered adaptor protein to provide new reagents for fluorimmunoassays. Anal. Chem. 74, 841–847 (2002).

    Article  CAS  Google Scholar 

  56. Poil, M.A. et al. Sensitive and specific colorimetric ELISAS for Staphylococcus aureus enterotoxins A and B in urine buffer. Toxicon 40, 1723–1726 (2002).

    Article  Google Scholar 

  57. Wu, S. et al. A review of the methods for detection of staphylococcus aureus enterotoxins. Toxins. 8, doi: 10.3390/toxins8070176 (2016).

    Google Scholar 

  58. Robinson, A. et al. Controversies affecting the future practice of clinical microbiology. J. Clin. Microbiol. 37, 883–889 (1999).

    CAS  Google Scholar 

  59. Prevost, G. et al. Panton-Valentine leucocidin and gamma-hemolysin from Staphylococcus aureus ATCC 49775 are encoded by distinct genetic loci and have different biological activities. Infect. Immun. 63, 4121–4129 (1995).

    CAS  Google Scholar 

  60. Poojary, N.S., Ramlal, S., Urs, R.M., Sripathy, M.H. & Batra, H.V. Application of monoclonal antibodies generated against Panton-Valentine Leukocidin (PVL-S) toxin for specific identification of community acquired methicillin resistance Staphylococcus aureus. Microbiol. Res. 169, 924–930 (2014).

    Article  CAS  Google Scholar 

  61. Banada, P.P. et al. Highly Sensitive Detection of Staphylococcus aureus Directly from Patient Blood. PLoS One 7, e31126 (2012).

    Article  CAS  Google Scholar 

  62. Nijhuis, R.H., van Maarseveen, N.M., van Hannen, E.J., van Zwet, A.A. & Mascini E.M. A rapid and high-throughput screening approach for methicillin-resistant Staphylococcus aureus based on the combination of two different real-time PCR assays. J. Clin. Microbiol. 52, 2861–2867 (2014).

    Article  Google Scholar 

  63. Liu, Y. Zhang, J. & Ji, Y. PCR-based Approaches for the Detection of Clinical Methicillin-resistant Staphylococcus aureus. Open. Microbiol. J. 10, 45–56 (2016).

    Article  CAS  Google Scholar 

  64. Okolie, C.E., Wooldridge, K.G., Turner, D.P.J., Cockayne, A. & James, R. Development of a heptaplex PCR assay for identification of Staphylococcus aureus and CoNS with simultaneous detection of virulence and antibiotic resistance genes. BMC Microbiology 15, 157 (2015).

    Article  Google Scholar 

  65. Shen, F. et al. Digital isothermal quantification of nucleic acids via simultaneous chemical initiation of recombinase polymerase amplification reactions on SlipChip. Anal. Chem. 83, 3533–3540 (2011).

    Article  CAS  Google Scholar 

  66. Kelley, K. et al. Detection of Methicillin-Resistant Staphylococcus Aureus by a Duplex Droplet Digital PCR Assay. J. Clin. Microbiol. 51, 2033–2039 (2013).

    Article  Google Scholar 

  67. Yang, L., Li, P. & Liu, J. Progress in multifunctional surface-enhanced Raman scattering substrate for detection. RSC. Adv. 4, 49635–49646 (2014).

    Article  CAS  Google Scholar 

  68. Lu, X. et al. Detecting and Tracking Nosocomial Methicillin-Resistant Staphylococcus aureus Using a Microfluidic SERS Biosensor. Anal. Chem. 85, 2320–2327 (2013).

    Article  CAS  Google Scholar 

  69. Liu, J., Cheng, J. & Zhang, Y. Upconversion nanoparticle based LRET system for sensitive detection of MRSA DNA sequence. Biosens. Bioelectron. 43, 252–256 (2013).

    Article  CAS  Google Scholar 

  70. Chandan, H.R., Venkataramana, M., Kurkuri, M.D. & Balakrishna, G. Simple quantum dot bioprobe/label for sensitive detection of Staphylococcus aureus TNase. Sens. Actuators B. 222, 1201–1208 (2016).

    Article  CAS  Google Scholar 

  71. Cheng, D. et al. Dual Recognition Strategy for Specific and Sensitive Detection of Bacteria Using Aptamer-Coated Magnetic Beads and Antibiotic-Capped Gold Nanoclusters. Anal. Chem. 88, 820–825 (2016).

    Article  CAS  Google Scholar 

  72. Bandara, A.B. et al. Detection of methicillin-resistant staphylococci by biosensor assay consisting of nanoscale films on optical fiber long-period gratings. Biosens. Bioelectron. 70, 433–440 (2015).

    Article  CAS  Google Scholar 

  73. Tawil, N. et al. The differential detection of methicillin-resistant, methicillin-susceptible and borderline oxacillin-resistant Staphylococcus aureus by surface plasmon resonance. Biosens. Bioelectron. 49, 334–340 (2013)

    Article  CAS  Google Scholar 

  74. Nawattanapaiboon, K. et al. SPR-DNA array for detection of methicillin-resistant Staphylococcus aureus (MRSA) in combination with loop-mediated isothermal amplification. Biosens. Bioelectron. 15, 335–340 (2015).

    Article  Google Scholar 

  75. Wang, Z. et al. Label-free, electrochemical detection of methicillin-resistant staphylococcus aureus DNA with reduced graphene oxide-modified electrodes. Biosens. Bioelectron. 26, 3881–3886 (2011).

    Article  CAS  Google Scholar 

  76. Koydemir, H.C. et al. A Fully Microfabricated Electrochemical Sensor and its Implementation for Detection of Methicillin Resistance in Staphylococcus aureus. IEEE Sens. J. 14, 1844–1851 (2014).

    Article  CAS  Google Scholar 

  77. Watanabe, K. et al. A smart DNA sensing system for detecting methicillin-resistant Staphylococcus aureus using modified nanoparticle probes. Biosens. Bioelectron. 15, 419–423 (2015).

    Article  Google Scholar 

  78. Wang, T., Zhang, Z., Li, Y. & Xie, G. Amplified electrochemical detection of mecA gene in methicillin-resistant Staphylococcus aureus based on target recycling amplification and isothermal strand-displacement polymerization reaction. Sens. Actuators B. 221, 148–154 (2015).

    Article  CAS  Google Scholar 

  79. Corrigan, D.K. et al. Development of a PCR-free electrochemical point of care test for clinical detection of methicillin resistant Staphylococcus aureus (MRSA). Analyst 138, 6997–7005 (2013).

    Article  CAS  Google Scholar 

  80. Abeyrathne, C.D. et al. Lab on a chip sensor for rapid detection and antibiotic resistance determination of Staphylococcus aureus. Analyst 141, 1922–1929 (2016).

    Article  CAS  Google Scholar 

  81. Corrigan, D.K. et al. Impedimetric detection of single-stranded PCR products derived from methicillin resistant Staphylococcus aureus (MRSA) isolates. Biosens. Bioelectron. 34, 178–184 (2012).

    Article  CAS  Google Scholar 

  82. Lv, X. et al. Rapid and ultrasensitive electrochemical detection of multidrug-resistant bacteria based on nanostructured gold coated ITO electrode. ACS Appl. Mater. Interfaces. 6, 11025–11031 (2014).

    Article  CAS  Google Scholar 

  83. Prieto, J.L. et al. Monitoring sepsis using electrical cell profiling. Lab. Chip. 16, 4333–4340 (2016).

    Article  CAS  Google Scholar 

  84. Cihalova, K. et al. Particle-based immunochemical separation of methicillin resistant Staphylococcus aureus with indirect electrochemical detection of labeling oligonucleotides. Anal. Methods. 8, 5123–5128 (2016).

    Article  CAS  Google Scholar 

  85. Chen, Y.W., Wang, H., Hupert, M. & Soper S.A. Identification of methicillin-resistant Staphylococcus aureus using an integrated and modular microfluidic system. Analyst. 138, 1075–1083 (2013).

    Article  CAS  Google Scholar 

  86. Lafleur, L.K. et al. A rapid, instrument-free,sample-to-result nucleic acid amplification test. Lab. Chip. 16, 3777–3787 (2016).

    Article  CAS  Google Scholar 

  87. Croxatto, A., Prod’hom, G. & Greub, G. Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology. FEMS Microbiol. Rev. 36, 380–407 (2012).

    Article  CAS  Google Scholar 

  88. Jacovides, C.L. et al. Successful identification of pathogens by polymerase chain reaction (PCR)-based electron spray ionization time-of-flight mass spectrometry (ESI-TOF-MS) in culture-negative periprosthetic joint infection. J. Bone Joint Surg. Am. 94, 2247–2254 (2012).

    Article  Google Scholar 

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Hulme, J. Recent advances in the detection of methicillin resistant Staphylococcus aureus (MRSA). BioChip J 11, 89–100 (2017). https://doi.org/10.1007/s13206-016-1201-9

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