TRENDS AND DEVELOPMENTS IN MOLECULAR DIAGNOSTICS FOR ANTIBIOTIC RESISTANCE DETECTION
Abstrak
Antimicrobial Resistance (AMR) poses a global threat, necessitating a shift from slow culture-based methods (24–48 hours) to rapid molecular diagnostics to ensure timely targeted therapy. Methodology: This study employed a Systematic Literature Review (SLR) and bibliometric analysis of 10,776 Scopus-indexed articles (up to 2024) using the PRISMA protocol and VOSviewer for network visualization. Publications peaked in 2024, with the United States and China leading global contributions. Thematic analysis reveals a transition from basic genetic studies to advanced technologies like NGS, multiplex PCR, CRISPR-based systems, and microfluidic biosensors. Key markers include carbapenemase (blaNDM, blaKPC), colistin resistance (mcr-1), and ESBLs. Emerging trends emphasize AI integration and decentralized Point-of-Care (POC) testing. Conclusion: Molecular diagnostics are vital for Antimicrobial Stewardship. Despite technological leaps, clinical standardization and costs remain significant barriers. This mapping provides a strategic roadmap for enhancing global resistance surveillance and precision diagnostics.
Referensi
[1] S. Agrawal et al., “Analysis and recommendation system-based on PRISMA checklist to write systematic review,” Assess. Writ., vol. 61, 2024, doi: 10.1016/j.asw.2024.100866.
[2] N. R. Haddaway, M. J. Page, C. C. Pritchard, and L. A. McGuinness, “PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis,” Campbell Syst. Rev., vol. 18, no. 2, 2022, doi: 10.1002/cl2.1230.
[3] J. M. Merigó and J.-B. Yang, “A bibliometric analysis of operations research and management science,” Omega (United Kingdom), vol. 73, pp. 37–48, 2017, doi: 10.1016/j.omega.2016.12.004.
[4] I. Passas, “Bibliometric Analysis: The Main Steps,” Encyclopedia, vol. 4, no. 2, p. 0, 2024, doi: 10.3390/encyclopedia4020065.
[5] N. Donthu, S. Kumar, D. Mukherjee, N. Pandey, and W. M. Lim, “How to conduct a bibliometric analysis: An overview and guidelines,” J. Bus. Res., vol. 133, pp. 285–296, 2021, doi: 10.1016/j.jbusres.2021.04.070.
[6] D. Claxton et al., “Molecular analysis of retroviral transduction in chronic myelogenous leukemia,” Hum. Gene Ther., vol. 2, no. 4, pp. 317–321, 1991, doi: 10.1089/hum.1991.2.4-317.
[7] J. Oteo and M. Belén Aracil, “Molecular characterization of resistance mechanisms: Methicillin resistance Staphylococcus aureus, extended spectrum β-lactamases and carbapenemases,” Enferm. Infecc. Microbiol. Clin., vol. 33, no. S2, pp. 27–33, 2015, doi: 10.1016/S0213-005X(15)30012-4.
[8] J. Osei Sekyere, U. Govinden, L. A. Bester, and S. Y. Essack, “Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods,” J. Appl. Microbiol., vol. 121, no. 3, pp. 601–617, 2016, doi: 10.1111/jam.13169.
[9] P. Nordmann and L. Poirel, “Emerging and important antibiotic resistance in Gram negatives: Epidemiology, theory and practice,” Rev. Med. Suisse, vol. 10, no. 427, pp. 902–907, 2014, [Online]. Available: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84900537716&partnerID=40&md5=a83f59cce9ff6641908a9bf1f00ed74d
[10] A. C. Fluit, “Genetic methods for detecting bacterial resistance genes,” in Bacterial Resistance to Antimicrobials, Second Edition, Eijkman-Winkler Institute, University Medical Center Utrecht, Utrecht, Netherlands: CRC Press, 2007, pp. 183–227. doi: 10.1201/9781420008753.ch9.
[11] B. W. Shaheen, R. Nayak, and D. M. Boothe, “Antimicrobial resistance in bacterial pathogens: Mechanisms and PCR-based detection technologies,” in Veterinary PCR Diagnostics, Division of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079-9502, United States: Bentham Science Publishers Ltd., 2012, pp. 33–58. doi: 10.2174/978160805348311201010033.
[12] S. Miller, U. Karaoz, E. Brodie, and S. Dunbar, “Solid and suspension microarrays for microbial diagnostics,” in Methods in Microbiology, vol. 42, S. A. and T. Y.-W., Eds., Clinical Microbiology Laboratory, University of California, San Francisco, CA, United States: Academic Press Inc., 2015, pp. 395–431. doi: 10.1016/bs.mim.2015.04.002.
[13] J. Zhan et al., “Evaluatology: The science and engineering of evaluation,” BenchCouncil Trans. Benchmarks, Stand. Eval., vol. 4, no. 1, 2024, doi: 10.1016/j.tbench.2024.100162.
[14] Y. Dehong et al., “Nano-Bio-Analytical Systems for the Detection of Emerging Infectious Diseases,” in Surface Engineering and Functional Nanomaterials for Point-of-Care Analytical Devices, Zhejiang University, Department of Biomedical Engineering, Hangzhou, China: Springer Nature, 2024, pp. 147–172. [Online]. Available: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85216640577&partnerID=40&md5=675a45755431512a84f47b7ff2b6d3cf
[15] H. Frickmann, W. O. Masanta, and A. E. Zautner, “Emerging rapid resistance testing methods for clinical microbiology laboratories and their potential impact on patient management,” Biomed Res. Int., vol. 2014, 2014, doi: 10.1155/2014/375681.
[16] G. T. Walker, “Routine, Molecular, and Sequence-Based Antimicrobial Susceptibility Testing: Progression from Research Databases to Future Predictive Models,” Clin. Microbiol. Newsl., vol. 43, no. 19, pp. 167–172, 2021, doi: 10.1016/j.clinmicnews.2021.09.001.
[17] M. Harris, T. Fasolino, N. J. Davis, D. Ivankovic, and N. Brownlee, “Multiplex Detection of Antimicrobial Resistance Genes for Rapid Antibiotic Guidance of Urinary Tract Infections,” Microbiol. Res. (Pavia)., vol. 14, no. 2, pp. 591–602, 2023, doi: 10.3390/microbiolres14020041.
[18] N. Woodford and A. Sundsfjord, “Molecular detection of antibiotic resistance: When and where?,” J. Antimicrob. Chemother., vol. 56, no. 2, pp. 259–261, 2005, doi: 10.1093/jac/dki195.
[19] X. Jiang and Y. Ni, “Application of molecular diagnostic technology in detection of antimicrobial resistance,” Chinese J. Lab. Med., vol. 43, no. 7, pp. 702–706, 2020, doi: 10.3760/cma.j.cn114452-20200306-00190.
[20] J. N. B. de Cardenas, C. D. Garner, Y. Su, L. Tang, and R. T. Hayden, “Comparative Evaluation of Assays for Broad Detection of Molecular Resistance Mechanisms in Enterobacterales Isolates,” J. Clin. Microbiol., vol. 59, no. 11, 2021, doi: 10.1128/JCM.01033-21.
[21] M. Contreras, H. Mujica, and M. A. García-Amado, “Molecular tools of antibiotic resistance for Helicobacter pylori: an overview in Latin America,” Front. Gastroenterol., vol. 3, 2024, doi: 10.3389/fgstr.2024.1410816.
[22] E. Luby, A. Mark Ibekwe, J. Zilles, and A. Pruden, “Molecular methods for assessment of antibiotic resistance in agricultural ecosystems: Prospects and challenges,” J. Environ. Qual., vol. 45, no. 2, pp. 441–453, 2016, doi: 10.2134/jeq2015.07.0367.
[23] T. Zhang and B. Li, “Antibiotic resistance in water environment: Frontiers of fundamental research, risk assessment and control strategies,” Kexue Tongbao/Chinese Sci. Bull., vol. 65, no. 24, pp. 2543–2554, 2020, doi: 10.1360/TB-2020-0110.
[24] M. Benkova, O. Soukup, and J. Marek, “Antimicrobial susceptibility testing: currently used methods and devices and the near future in clinical practice,” J. Appl. Microbiol., vol. 129, no. 4, pp. 806–822, 2020, doi: 10.1111/jam.14704.
[25] M. R. Pulido, M. García-Quintanilla, R. Martín-Peña, J. M. Cisneros, and M. J. McConnell, “Progress on the development of rapid methods for antimicrobial susceptibility testing,” J. Antimicrob. Chemother., vol. 68, no. 12, pp. 2710–2717, 2013, doi: 10.1093/jac/dkt253.
[26] A. Aroonnual, T. Janvilisri, P. Ounjai, and S. Chankhamhaengdecha, “Microfluidics: Innovative approaches for rapid diagnosis of antibiotic-resistant bacteria,” Essays Biochem., vol. 61, no. 1, pp. 91–101, 2017, doi: 10.1042/EBC20160059.
[27] T. A. Leski et al., “Molecular Characterization of Multidrug Resistant Hospital Isolates Using the Antimicrobial Resistance Determinant Microarray,” PLoS One, vol. 8, no. 7, 2013, doi: 10.1371/journal.pone.0069507.
[28] C. P. Barrera-Patiño, J. M. Soares, K. C. Blanco, N. M. Inada, and V. S. Bagnato, “Implementation of machine learning study in Staphylococcus aureus’s FTIR spectra to antibiotic resistance identification,” in Progress in Biomedical Optics and Imaging - Proceedings of SPIE, D. T., P. J., and W. M.X., Eds., São Carlos Institute of Physics, University of São Paulo, Avenida Trabalhador São-carlense no400, Parque Arnold Schimidt, São Paulo, São Carlos, CEP 13566-590, Brazil: SPIE, 2024. doi: 10.1117/12.3001639.
[29] G. Caruso, “Antibiotic resistance in Escherichia coli from farm livestock and related analytical methods: A review,” J. AOAC Int., vol. 101, no. 4, pp. 916–922, 2018, doi: 10.5740/jaoacint.17-0445.
[30] L. Clarindo Lopes, A. Koushanpour, K. Wiebe, and S. Kuss, “Antibiotic Resistance Detection in Pseudomonas aeruginosa: Recent Strategies, Advances, and Challenges,” Anal. Sens., vol. 4, no. 4, 2024, doi: 10.1002/anse.202300058.
[31] D. Yamin et al., “Current and Future Technologies for the Detection of Antibiotic-Resistant Bacteria,” Diagnostics, vol. 13, no. 20, 2023, doi: 10.3390/diagnostics13203246.
[32] J. Horn et al., “Next-generation microbiological testing in intraabdominal infections with PCR technology,” Langenbeck’s Arch. Surg., vol. 409, no. 1, 2024, doi: 10.1007/s00423-024-03298-9.
[33] G. Vrenna et al., “Integrating Diagnostic Approaches in Infant Bacterial Meningitis Caused by a Non-K1 Escherichia coli: A Case Report,” Antibiotics, vol. 13, no. 12, 2024, doi: 10.3390/antibiotics13121144.
[34] Q. Yang et al., “Department-specific patterns of bacterial communities and antibiotic resistance in hospital indoor environments,” Appl. Microbiol. Biotechnol., vol. 108, no. 1, 2024, doi: 10.1007/s00253-024-13326-9.
[35] A. J. Greeshma, R. N. Ramani Pushpa, K. Lakshmi Kavitha, and T. Srinivasa Rao, “Efficacy of Resveratrol and Ursolic Acid on Biofilm Inhibition and Antimicrobial Resistance of Streptococcus uberis,” Indian J. Anim. Res., vol. 58, no. 12, pp. 2177–2183, 2024, doi: 10.18805/IJAR.B-4697.
[36] D. A. Negrón et al., “Loop-mediated isothermal amplification assays for the detection of antimicrobial resistance elements in Vibrio cholera,” BMC Bioinformatics, vol. 25, no. 1, 2024, doi: 10.1186/s12859-024-06001-3.
[2] N. R. Haddaway, M. J. Page, C. C. Pritchard, and L. A. McGuinness, “PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis,” Campbell Syst. Rev., vol. 18, no. 2, 2022, doi: 10.1002/cl2.1230.
[3] J. M. Merigó and J.-B. Yang, “A bibliometric analysis of operations research and management science,” Omega (United Kingdom), vol. 73, pp. 37–48, 2017, doi: 10.1016/j.omega.2016.12.004.
[4] I. Passas, “Bibliometric Analysis: The Main Steps,” Encyclopedia, vol. 4, no. 2, p. 0, 2024, doi: 10.3390/encyclopedia4020065.
[5] N. Donthu, S. Kumar, D. Mukherjee, N. Pandey, and W. M. Lim, “How to conduct a bibliometric analysis: An overview and guidelines,” J. Bus. Res., vol. 133, pp. 285–296, 2021, doi: 10.1016/j.jbusres.2021.04.070.
[6] D. Claxton et al., “Molecular analysis of retroviral transduction in chronic myelogenous leukemia,” Hum. Gene Ther., vol. 2, no. 4, pp. 317–321, 1991, doi: 10.1089/hum.1991.2.4-317.
[7] J. Oteo and M. Belén Aracil, “Molecular characterization of resistance mechanisms: Methicillin resistance Staphylococcus aureus, extended spectrum β-lactamases and carbapenemases,” Enferm. Infecc. Microbiol. Clin., vol. 33, no. S2, pp. 27–33, 2015, doi: 10.1016/S0213-005X(15)30012-4.
[8] J. Osei Sekyere, U. Govinden, L. A. Bester, and S. Y. Essack, “Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods,” J. Appl. Microbiol., vol. 121, no. 3, pp. 601–617, 2016, doi: 10.1111/jam.13169.
[9] P. Nordmann and L. Poirel, “Emerging and important antibiotic resistance in Gram negatives: Epidemiology, theory and practice,” Rev. Med. Suisse, vol. 10, no. 427, pp. 902–907, 2014, [Online]. Available: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84900537716&partnerID=40&md5=a83f59cce9ff6641908a9bf1f00ed74d
[10] A. C. Fluit, “Genetic methods for detecting bacterial resistance genes,” in Bacterial Resistance to Antimicrobials, Second Edition, Eijkman-Winkler Institute, University Medical Center Utrecht, Utrecht, Netherlands: CRC Press, 2007, pp. 183–227. doi: 10.1201/9781420008753.ch9.
[11] B. W. Shaheen, R. Nayak, and D. M. Boothe, “Antimicrobial resistance in bacterial pathogens: Mechanisms and PCR-based detection technologies,” in Veterinary PCR Diagnostics, Division of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079-9502, United States: Bentham Science Publishers Ltd., 2012, pp. 33–58. doi: 10.2174/978160805348311201010033.
[12] S. Miller, U. Karaoz, E. Brodie, and S. Dunbar, “Solid and suspension microarrays for microbial diagnostics,” in Methods in Microbiology, vol. 42, S. A. and T. Y.-W., Eds., Clinical Microbiology Laboratory, University of California, San Francisco, CA, United States: Academic Press Inc., 2015, pp. 395–431. doi: 10.1016/bs.mim.2015.04.002.
[13] J. Zhan et al., “Evaluatology: The science and engineering of evaluation,” BenchCouncil Trans. Benchmarks, Stand. Eval., vol. 4, no. 1, 2024, doi: 10.1016/j.tbench.2024.100162.
[14] Y. Dehong et al., “Nano-Bio-Analytical Systems for the Detection of Emerging Infectious Diseases,” in Surface Engineering and Functional Nanomaterials for Point-of-Care Analytical Devices, Zhejiang University, Department of Biomedical Engineering, Hangzhou, China: Springer Nature, 2024, pp. 147–172. [Online]. Available: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85216640577&partnerID=40&md5=675a45755431512a84f47b7ff2b6d3cf
[15] H. Frickmann, W. O. Masanta, and A. E. Zautner, “Emerging rapid resistance testing methods for clinical microbiology laboratories and their potential impact on patient management,” Biomed Res. Int., vol. 2014, 2014, doi: 10.1155/2014/375681.
[16] G. T. Walker, “Routine, Molecular, and Sequence-Based Antimicrobial Susceptibility Testing: Progression from Research Databases to Future Predictive Models,” Clin. Microbiol. Newsl., vol. 43, no. 19, pp. 167–172, 2021, doi: 10.1016/j.clinmicnews.2021.09.001.
[17] M. Harris, T. Fasolino, N. J. Davis, D. Ivankovic, and N. Brownlee, “Multiplex Detection of Antimicrobial Resistance Genes for Rapid Antibiotic Guidance of Urinary Tract Infections,” Microbiol. Res. (Pavia)., vol. 14, no. 2, pp. 591–602, 2023, doi: 10.3390/microbiolres14020041.
[18] N. Woodford and A. Sundsfjord, “Molecular detection of antibiotic resistance: When and where?,” J. Antimicrob. Chemother., vol. 56, no. 2, pp. 259–261, 2005, doi: 10.1093/jac/dki195.
[19] X. Jiang and Y. Ni, “Application of molecular diagnostic technology in detection of antimicrobial resistance,” Chinese J. Lab. Med., vol. 43, no. 7, pp. 702–706, 2020, doi: 10.3760/cma.j.cn114452-20200306-00190.
[20] J. N. B. de Cardenas, C. D. Garner, Y. Su, L. Tang, and R. T. Hayden, “Comparative Evaluation of Assays for Broad Detection of Molecular Resistance Mechanisms in Enterobacterales Isolates,” J. Clin. Microbiol., vol. 59, no. 11, 2021, doi: 10.1128/JCM.01033-21.
[21] M. Contreras, H. Mujica, and M. A. García-Amado, “Molecular tools of antibiotic resistance for Helicobacter pylori: an overview in Latin America,” Front. Gastroenterol., vol. 3, 2024, doi: 10.3389/fgstr.2024.1410816.
[22] E. Luby, A. Mark Ibekwe, J. Zilles, and A. Pruden, “Molecular methods for assessment of antibiotic resistance in agricultural ecosystems: Prospects and challenges,” J. Environ. Qual., vol. 45, no. 2, pp. 441–453, 2016, doi: 10.2134/jeq2015.07.0367.
[23] T. Zhang and B. Li, “Antibiotic resistance in water environment: Frontiers of fundamental research, risk assessment and control strategies,” Kexue Tongbao/Chinese Sci. Bull., vol. 65, no. 24, pp. 2543–2554, 2020, doi: 10.1360/TB-2020-0110.
[24] M. Benkova, O. Soukup, and J. Marek, “Antimicrobial susceptibility testing: currently used methods and devices and the near future in clinical practice,” J. Appl. Microbiol., vol. 129, no. 4, pp. 806–822, 2020, doi: 10.1111/jam.14704.
[25] M. R. Pulido, M. García-Quintanilla, R. Martín-Peña, J. M. Cisneros, and M. J. McConnell, “Progress on the development of rapid methods for antimicrobial susceptibility testing,” J. Antimicrob. Chemother., vol. 68, no. 12, pp. 2710–2717, 2013, doi: 10.1093/jac/dkt253.
[26] A. Aroonnual, T. Janvilisri, P. Ounjai, and S. Chankhamhaengdecha, “Microfluidics: Innovative approaches for rapid diagnosis of antibiotic-resistant bacteria,” Essays Biochem., vol. 61, no. 1, pp. 91–101, 2017, doi: 10.1042/EBC20160059.
[27] T. A. Leski et al., “Molecular Characterization of Multidrug Resistant Hospital Isolates Using the Antimicrobial Resistance Determinant Microarray,” PLoS One, vol. 8, no. 7, 2013, doi: 10.1371/journal.pone.0069507.
[28] C. P. Barrera-Patiño, J. M. Soares, K. C. Blanco, N. M. Inada, and V. S. Bagnato, “Implementation of machine learning study in Staphylococcus aureus’s FTIR spectra to antibiotic resistance identification,” in Progress in Biomedical Optics and Imaging - Proceedings of SPIE, D. T., P. J., and W. M.X., Eds., São Carlos Institute of Physics, University of São Paulo, Avenida Trabalhador São-carlense no400, Parque Arnold Schimidt, São Paulo, São Carlos, CEP 13566-590, Brazil: SPIE, 2024. doi: 10.1117/12.3001639.
[29] G. Caruso, “Antibiotic resistance in Escherichia coli from farm livestock and related analytical methods: A review,” J. AOAC Int., vol. 101, no. 4, pp. 916–922, 2018, doi: 10.5740/jaoacint.17-0445.
[30] L. Clarindo Lopes, A. Koushanpour, K. Wiebe, and S. Kuss, “Antibiotic Resistance Detection in Pseudomonas aeruginosa: Recent Strategies, Advances, and Challenges,” Anal. Sens., vol. 4, no. 4, 2024, doi: 10.1002/anse.202300058.
[31] D. Yamin et al., “Current and Future Technologies for the Detection of Antibiotic-Resistant Bacteria,” Diagnostics, vol. 13, no. 20, 2023, doi: 10.3390/diagnostics13203246.
[32] J. Horn et al., “Next-generation microbiological testing in intraabdominal infections with PCR technology,” Langenbeck’s Arch. Surg., vol. 409, no. 1, 2024, doi: 10.1007/s00423-024-03298-9.
[33] G. Vrenna et al., “Integrating Diagnostic Approaches in Infant Bacterial Meningitis Caused by a Non-K1 Escherichia coli: A Case Report,” Antibiotics, vol. 13, no. 12, 2024, doi: 10.3390/antibiotics13121144.
[34] Q. Yang et al., “Department-specific patterns of bacterial communities and antibiotic resistance in hospital indoor environments,” Appl. Microbiol. Biotechnol., vol. 108, no. 1, 2024, doi: 10.1007/s00253-024-13326-9.
[35] A. J. Greeshma, R. N. Ramani Pushpa, K. Lakshmi Kavitha, and T. Srinivasa Rao, “Efficacy of Resveratrol and Ursolic Acid on Biofilm Inhibition and Antimicrobial Resistance of Streptococcus uberis,” Indian J. Anim. Res., vol. 58, no. 12, pp. 2177–2183, 2024, doi: 10.18805/IJAR.B-4697.
[36] D. A. Negrón et al., “Loop-mediated isothermal amplification assays for the detection of antimicrobial resistance elements in Vibrio cholera,” BMC Bioinformatics, vol. 25, no. 1, 2024, doi: 10.1186/s12859-024-06001-3.
Diterbitkan
2025-12-24
##submission.howToCite##
IsangS. A. N. (2025). TRENDS AND DEVELOPMENTS IN MOLECULAR DIAGNOSTICS FOR ANTIBIOTIC RESISTANCE DETECTION. Journal of Health, Technology and Science (JHTS), 6(4), 304-316. https://doi.org/10.47918/jhts.v6i4.2668
Bagian
Articles
##submission.copyrightStatement##
##submission.license.cc.by4.footer##
