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Fenotipik Karbapenemaz Tespit Yöntemlerinin İncelenmesi

Year 2025, Volume: 5 Issue: 3, 114 - 120, 23.09.2025

Abstract

Karbapenemler, Gram-negatif, Gram-pozitif ve anaerobik bakteriler tarafından kaynaklanan çoklu ilaç dirençli enfeksiyonların tedavisinde kullanılan geniş spektrumlu antibiyotiklerdir. Ancak, bu antibiyotikleri aşırı kullanımı, karbapenem dirençli bakterilerin (CRB) artışına yol açmış ve bu durum tedavi açısından önemli zorluklar yaratmıştır. Karbapenem direnci, öncelikle karbapenemleri hidrolize eden ve genellikle plazmidler tarafından kodlanan karbapenemaz enzimlerinin üretimiyle aracılık edilmektedir, bu da genetik materyalin yatay transferini kolaylaştırır. Karbapenemaz üreten organizmaların hızlı bir şekilde tespiti, etkili antimikrobiyal yönetim ve direnç yayılmasının önlenmesi için çok önemlidir. Karbapenemazları tespit etmek için fenotipik yöntemler arasında disk difüzyon, minimum inhibitör konsantrasyon (MIC) yöntemleri, gradyan difüzyon, otomatik sistemler ve kromojenik ortamlar bulunmaktadır. Carba NP testi ve immünokromatografik analizler gibi daha ileri teknikler, direnç profillerinin hızlı bir şekilde tanımlanmasını sağlarken, spektrofotometrik analizler enzimatik hidrolizi tespit eder. Yöntem seçimi, duyarlılık, özgüllük ve klinik bağlama bağlıdır. Erken ve doğru tespit, tedavinin zamanında ayarlanmasına olanak tanır, hasta sonuçlarını optimize eder ve geniş spektrumlu antibiyotikleri yanlış kullanımı sınırlayarak hastaların tedavi süreçlerini iyileştirir.

Project Number

yok

References

  • 1. Armstrong T, Fenn SJ, Hardie KR. JMM Profile: Carbapenems: a broad-spectrum antibiotic. J Med Microbiol. 2021;70(12):001462.
  • 2. Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: Past, Present, and Future. Antimicrob Agents Chemother. 2011, 55, 4943–4960.
  • 3. Otlu B, Yakupoğulları Y, Gürsoy Nc, Duman Y, Bayındır Y, Tekerekoğlu MS, et all. Co-Production of OXA-48 and NDM-1 Carbapenemases in Providencia rettgeri: the First Report. Mikrobiyol Bul. 2018; 52(3): 300-307.
  • 4. Jean SS, Harnod D, Hsueh PR. Global Threat of Carbapenem-Resistant Gram-Negative Bacteria. Front Cell Infect Microbiol. 2022; 15(12): 823684.
  • 5. Zhu Y, Huang WE, Yang Q. Clinical Perspective of Antimicrobial Resistance in Bacteria. Infect Drug Resist. 2022; 2:15:735-746.
  • 6. Duman Y, Ersoy Y, Tanriverdi ES, Otlu B, Toplu SA, Gozükara G, et all. Oral colonization of Acinetobacter baumannii in intensive care units: Risk factors, incidence, molecular epidemiology, association with the occur of pneumonia and sepsis, and infection control measures. Iranıan J Basıc Med Scı. 2022;25 (2): 239-244.
  • 7. Codjoe FS, Donkor ES. Carbapenem resistance: a review. Med Sci. 2018;6:1.
  • 8. Lepe JA, Martínez-Martínez L. Resistance mechanisms in Gram-negative bacteria. Med Intensiva. 2022;46(7):392-402.
  • 9. Elshamy AA, Aboshanab KM. A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options. Future Sci OA. 2020;6:FSO438.
  • 10. Paudel R, Shrestha E, Chapagain B, Tiwari BR. Carbapenemase producing Gram negative bacteria: Review of resistance and detection methods. Diagn Microbiol Infect Dis. 2024; 110: 116370.
  • 11. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 15.0, 2025. http://www.eucast.org/clinical_breakpoints
  • 12. CLSI. Performance standards for antimicrobial susceptibility testing. 35th ed. CLSI supplement M100. Clinical and laboratory standards institute; 2025. ISBN: 978-1-68440-263-2
  • 13. Aruhomukama D. Review of phenotypic assays for detection of extended-spectrum β-lactamases and carbapenemases: a microbiology laboratory bench guide. Afr Health Sci. 2020;20(3):1090-1108.
  • 14. Girlich D, Halimi D, Zambardi G, Nordmann P. Evaluation of Etest strips for detection of KPC and metallo-carbapenemases in enterobacteriaceae. Diagn Microbiol Infect Dis. 2013;77:200–1.
  • 15. Zarakolu P, Day KM, Sidjabat HE, Kamolvit W, Lanyon CV, Cummings SP, et al. Evaluation of a new chromogenic medium, chromID OXA-48, for recovery of carbapenemase-producing Enterobacteriaceae from patients at a university hospital in Turkey. Eur J Clin Microbiol Infect Dis. 2015;34:519–525.
  • 16. Seah C, Low DE, Patel SN, Melano RG. Comparative evaluation of a chromogenic agar medium, the Modified Hodge Test, and a battery of meropenem-inhibitor discs for detection of carbapenemase activity in enterobacteriaceae. J Clin Microbiol. 2011;49:1965–9.
  • 17. Caliskan-Aydogan O, Alocilja EC. A Review of Carbapenem Resistance in Enterobacterales and Its Detection Techniques. Microorganisms. 2023: 3;11(6):1491.
  • 18. Pandurangan S, BegumEsak S, Narayanasamy A. Phenotypic detection methods of carbapenemase production in Enterobacteriaceae. Int J Curr Microbiol Appl Sci. 2015;4:547–52.
  • 19. Rabaan AA, Eljaaly K, Alhumaid S, Albayat H, Al-Adsani W, Sabour AA, et al. An overview on phenotypic and genotypic characterisation of carbapenem-resistant enterobacterales. Medicina. 2022;58:1675.
  • 20. Simner PJ, Pitout JDD, Dingle TC. Laboratory detection of carbapenemases among Gram-negative organisms. Clin Microbiol Rev. 2024; 10;37(4):e0005422.
  • 21. Suriya R V, Kv L, Feliciana J H, R A. Diagnostic Test Precision of Modified Carbapenem Inactivation Method and Carbapenemase Nordmann-Poirel Test for Phenotypic Detection of Carbapenemase Production in Enterobacterales: A Systematic Review. Cureus. 2024; 20;16(8):e67322.
  • 22. Pasteran F, Veliz O, Ceriana P, Lucero C, Rapoport M, Albornoz E, et al. Evaluation of the blue-carba test for rapid detection of carbapenemases in Gram-negative Bacilli. J Clin Microbiol. 2015;53:1996–1998.
  • 23. Buehler SS, Madison B, Snyder SR, Derzon J, Cornish NE, Saubolle MA, et al. Effectiveness of Practices To Increase Timeliness of Providing Targeted Therapy for Inpatients with Bloodstream Infections: A Laboratory Medicine Best Practices Systematic Review and Meta-analysis. Clin Microbiol Rev. 2016; 29: 59–103.
  • 24. Tsai YM, Wang S, Chiu HC, Kao CY, Wen LL. Combination of modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) for phenotypic detection of carbapenemase-producing Enterobacteriaceae. BMC Microbiol. 2020; 20:315.
  • 25. Bernabeu S, Poirel L, Nordmann P. Spectrophotometry-based detection of carbapenemase producers among Enterobacteriaceae. Diagn Microbiol Infect Dis. 2012;74:88–90.
  • 26. Gato E, Anantharajah A, Arroyo MJ, Artacho MJ, Caballero J de D, Candela A, et al. Multicenter performance evaluation of MALDI-TOF MS for rapid detection of carbapenemase activity in Enterobacterales: the future of networking data analysis with online software. Front Microbiol. 2022;12.
  • 27. Süzük Yıldız S, Şimşek H, Bakkaloğlu Z, Numanoğlu Çevik Y, Hekimoğlu CH, Kılıç S ve ark. The Epidemiology of Carbapenemases in Escherichia coli and Klebsiella pneumoniae Isolated in 2019 in Turkey. Mikrobiyol Bul 2021;55(1):1-16.
  • 28. Duman Y, Ersoy Y, Gürsoy NC, Toplu S, Otlu B. A silent outbreak due to Klebsiella pneumoniae that co-produced NDM-1 and OXA-48 carbapenemases, and infection control measures. Iranian J Basıc Med Scıen. 2020; 23 (1): 46-50.
  • 29. Gordon N, Bawa R, Palmateer G. Carbapenem-Resistant Enterobacteriaceae Testing in 45 Minutes Using an Electronic Sensor. Curr. Issues Med. Diagn. Imaging 2021, 4, 1–18

A Review of Phenotypic Carbapenemase Detection Methods

Year 2025, Volume: 5 Issue: 3, 114 - 120, 23.09.2025

Abstract

Carbapenems are broad-spectrum antibiotics used to treat multidrug-resistant infections caused by Gram-negative, Gram-positive, and anaerobic bacteria. However, the overuse of these antibiotics has led to the rise of carbapenem-resistant bacteria (CRB), which present significant treatment challenges. Carbapenem resistance is primarily mediated by the production of carbapenemase enzymes, which hydrolyze carbapenems and are often encoded by plasmids, facilitating horizontal gene transfer. Rapid detection of carbapenemase-producing organisms is crucial for effective antimicrobial stewardship and preventing the spread of resistance. Phenotypic methods for detecting carbapenemases include disk diffusion, minimum inhibitory concentration (MIC) methods, gradient diffusion, automated systems, and chromogenic media. More advanced techniques, such as the Carba NP test and immunochromatographic assays, provide rapid identification of resistance profiles, while spectrophotometric analysis detects enzymatic hydrolysis. The choice of method depends on sensitivity, specificity, and clinical context. Early and accurate detection allows for timely adjustments to treatment, optimizing patient outcomes and limiting the misuse of broad-spectrum antibiotics.

Ethical Statement

We hereby confirm that our manuscript entitled “A Review of Phenotypic Carbapenemase Detection Methods” is a narrative review article based entirely on previously published data and does not involve any human or animal subjects, experiments, or patient-identifiable information. Therefore, ethical approval was not required for this type of article.

Supporting Institution

No financial or personal relationships with other individuals or organizations have influenced the content or interpretation of this work.

Project Number

yok

Thanks

We hope that the manuscript will be of interest to your readers and look forward to your favorable consideration.

References

  • 1. Armstrong T, Fenn SJ, Hardie KR. JMM Profile: Carbapenems: a broad-spectrum antibiotic. J Med Microbiol. 2021;70(12):001462.
  • 2. Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: Past, Present, and Future. Antimicrob Agents Chemother. 2011, 55, 4943–4960.
  • 3. Otlu B, Yakupoğulları Y, Gürsoy Nc, Duman Y, Bayındır Y, Tekerekoğlu MS, et all. Co-Production of OXA-48 and NDM-1 Carbapenemases in Providencia rettgeri: the First Report. Mikrobiyol Bul. 2018; 52(3): 300-307.
  • 4. Jean SS, Harnod D, Hsueh PR. Global Threat of Carbapenem-Resistant Gram-Negative Bacteria. Front Cell Infect Microbiol. 2022; 15(12): 823684.
  • 5. Zhu Y, Huang WE, Yang Q. Clinical Perspective of Antimicrobial Resistance in Bacteria. Infect Drug Resist. 2022; 2:15:735-746.
  • 6. Duman Y, Ersoy Y, Tanriverdi ES, Otlu B, Toplu SA, Gozükara G, et all. Oral colonization of Acinetobacter baumannii in intensive care units: Risk factors, incidence, molecular epidemiology, association with the occur of pneumonia and sepsis, and infection control measures. Iranıan J Basıc Med Scı. 2022;25 (2): 239-244.
  • 7. Codjoe FS, Donkor ES. Carbapenem resistance: a review. Med Sci. 2018;6:1.
  • 8. Lepe JA, Martínez-Martínez L. Resistance mechanisms in Gram-negative bacteria. Med Intensiva. 2022;46(7):392-402.
  • 9. Elshamy AA, Aboshanab KM. A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options. Future Sci OA. 2020;6:FSO438.
  • 10. Paudel R, Shrestha E, Chapagain B, Tiwari BR. Carbapenemase producing Gram negative bacteria: Review of resistance and detection methods. Diagn Microbiol Infect Dis. 2024; 110: 116370.
  • 11. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 15.0, 2025. http://www.eucast.org/clinical_breakpoints
  • 12. CLSI. Performance standards for antimicrobial susceptibility testing. 35th ed. CLSI supplement M100. Clinical and laboratory standards institute; 2025. ISBN: 978-1-68440-263-2
  • 13. Aruhomukama D. Review of phenotypic assays for detection of extended-spectrum β-lactamases and carbapenemases: a microbiology laboratory bench guide. Afr Health Sci. 2020;20(3):1090-1108.
  • 14. Girlich D, Halimi D, Zambardi G, Nordmann P. Evaluation of Etest strips for detection of KPC and metallo-carbapenemases in enterobacteriaceae. Diagn Microbiol Infect Dis. 2013;77:200–1.
  • 15. Zarakolu P, Day KM, Sidjabat HE, Kamolvit W, Lanyon CV, Cummings SP, et al. Evaluation of a new chromogenic medium, chromID OXA-48, for recovery of carbapenemase-producing Enterobacteriaceae from patients at a university hospital in Turkey. Eur J Clin Microbiol Infect Dis. 2015;34:519–525.
  • 16. Seah C, Low DE, Patel SN, Melano RG. Comparative evaluation of a chromogenic agar medium, the Modified Hodge Test, and a battery of meropenem-inhibitor discs for detection of carbapenemase activity in enterobacteriaceae. J Clin Microbiol. 2011;49:1965–9.
  • 17. Caliskan-Aydogan O, Alocilja EC. A Review of Carbapenem Resistance in Enterobacterales and Its Detection Techniques. Microorganisms. 2023: 3;11(6):1491.
  • 18. Pandurangan S, BegumEsak S, Narayanasamy A. Phenotypic detection methods of carbapenemase production in Enterobacteriaceae. Int J Curr Microbiol Appl Sci. 2015;4:547–52.
  • 19. Rabaan AA, Eljaaly K, Alhumaid S, Albayat H, Al-Adsani W, Sabour AA, et al. An overview on phenotypic and genotypic characterisation of carbapenem-resistant enterobacterales. Medicina. 2022;58:1675.
  • 20. Simner PJ, Pitout JDD, Dingle TC. Laboratory detection of carbapenemases among Gram-negative organisms. Clin Microbiol Rev. 2024; 10;37(4):e0005422.
  • 21. Suriya R V, Kv L, Feliciana J H, R A. Diagnostic Test Precision of Modified Carbapenem Inactivation Method and Carbapenemase Nordmann-Poirel Test for Phenotypic Detection of Carbapenemase Production in Enterobacterales: A Systematic Review. Cureus. 2024; 20;16(8):e67322.
  • 22. Pasteran F, Veliz O, Ceriana P, Lucero C, Rapoport M, Albornoz E, et al. Evaluation of the blue-carba test for rapid detection of carbapenemases in Gram-negative Bacilli. J Clin Microbiol. 2015;53:1996–1998.
  • 23. Buehler SS, Madison B, Snyder SR, Derzon J, Cornish NE, Saubolle MA, et al. Effectiveness of Practices To Increase Timeliness of Providing Targeted Therapy for Inpatients with Bloodstream Infections: A Laboratory Medicine Best Practices Systematic Review and Meta-analysis. Clin Microbiol Rev. 2016; 29: 59–103.
  • 24. Tsai YM, Wang S, Chiu HC, Kao CY, Wen LL. Combination of modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) for phenotypic detection of carbapenemase-producing Enterobacteriaceae. BMC Microbiol. 2020; 20:315.
  • 25. Bernabeu S, Poirel L, Nordmann P. Spectrophotometry-based detection of carbapenemase producers among Enterobacteriaceae. Diagn Microbiol Infect Dis. 2012;74:88–90.
  • 26. Gato E, Anantharajah A, Arroyo MJ, Artacho MJ, Caballero J de D, Candela A, et al. Multicenter performance evaluation of MALDI-TOF MS for rapid detection of carbapenemase activity in Enterobacterales: the future of networking data analysis with online software. Front Microbiol. 2022;12.
  • 27. Süzük Yıldız S, Şimşek H, Bakkaloğlu Z, Numanoğlu Çevik Y, Hekimoğlu CH, Kılıç S ve ark. The Epidemiology of Carbapenemases in Escherichia coli and Klebsiella pneumoniae Isolated in 2019 in Turkey. Mikrobiyol Bul 2021;55(1):1-16.
  • 28. Duman Y, Ersoy Y, Gürsoy NC, Toplu S, Otlu B. A silent outbreak due to Klebsiella pneumoniae that co-produced NDM-1 and OXA-48 carbapenemases, and infection control measures. Iranian J Basıc Med Scıen. 2020; 23 (1): 46-50.
  • 29. Gordon N, Bawa R, Palmateer G. Carbapenem-Resistant Enterobacteriaceae Testing in 45 Minutes Using an Electronic Sensor. Curr. Issues Med. Diagn. Imaging 2021, 4, 1–18
There are 29 citations in total.

Details

Primary Language English
Subjects Clinical Microbiology
Journal Section Review Articles
Authors

Yücel Duman 0000-0002-9090-2096

Altan Akıneden 0000-0002-1434-6892

Selçuk Türkel 0000-0001-5392-8679

Project Number yok
Publication Date September 23, 2025
Submission Date April 10, 2025
Acceptance Date August 25, 2025
Published in Issue Year 2025 Volume: 5 Issue: 3

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