Kombinasyon Disk Testi
Özet
Karbapenemaz üreten Enterobacterales (KÜE) suşlarının küresel yayılımı, halk sağlığı açısından ciddi bir tehdit oluşturmaktadır. Bu direnç mekanizmasının doğru ve hızlı saptanması, enfeksiyon kontrolü ve hastaya özgü tedavi rejimlerinin belirlenmesi açısından çok önemlidir. Fenotipik testler arasında yer alan kombinasyon disk testi (KDT), özgül inhibitörler kullanarak karbapenemaz sınıflarını ayırt etme yeteneğiyle öne çıkar. Test, özellikle tek tip Sınıf A (KPC) veya Sınıf B (MBL) karbapenemaz üreten izolatlarda başarılı sonuçlar verse de Sınıf D (OXA-48 benzeri) enzimlerini saptayamaması ve aynı anda birden çok karbapenemaz üreten izolatlarda başarısız olması gibi sınırlamaları vardır. Ayrıca, AmpC ß-laktamazları veya bazı OXA enzimleri nedeniyle yanlış pozitif sonuçlar ortaya çıkabilir. Lateral akış immünoassayları gibi daha yeni, hızlı ve kapsamlı teknolojilerin geliştirilmesiyle KDT'nin tanısal rolü değişmektedir. Bu makalede, KDT'nin temel prensipleri, yöntemi, ticari kitleri, tanısal performansı, avantajları ve sınırlılıkları, güncel araştırma verileriyle ayrıntılı şekilde incelenmiştir.
The global dissemination of carbapenemase-producing Enterobacterales (CPE) strains represents a serious public health concern. Accurate and rapid detection of this resistance mechanism is crucial for effective infection control and for determining patient-specific therapeutic regimens. Among phenotypic methods, the combination disk test (CDT) stands out with its ability to differentiate between carbapenemase classes using specific inhibitors. Although the test yields reliable results for isolates producing a single carbapenemase class—such as Class A (KPC) or Class B (MBL)—it has significant limitations in detecting Class D (OXA-48-like) enzymes and often fails when multiple carbapenemases are co-produced. Furthermore, false-positive results may occur due to the presence of AmpC β-lactamases or certain OXA enzymes. With the development of newer, faster, and more comprehensive technologies such as lateral flow immunoassays, the diagnostic role of CDT is evolving. This article provides a detailed analysis of the fundamental principles, methodology, commercial kits, diagnostic performance, advantages, and limitations of the combination disk test, supported by up-to-date research data.
Referanslar
Hrabak J, Chudáčková E, Papagiannitsis CC. Detection of carbapenemases in Enterobacteriaceae: a challenge for diagnostic microbiological laboratories. Clinical Microbiology and Infection. 2014;20(9): 839-853.
Tamma P D, Simner PJ. Phenotypic Detection of Carbapenemase-Producing Organisms from Clinical Isolates. Journal of Clinical Microbiology. 2018;56(11): e01140-18.
Bartolini A, Frasson I, Cavallaro A, Richter SN, Palù G. Comparison of phenotypic methods for the detection of carbapenem non-susceptible Enterobacteriaceae. Gut Pathogens. 2014;6(1), 13.
Pournaras S, Poulou A, Tsakris A. Inhibitor-based methods for the detection of KPC carbapenemase-producing Enterobacteriaceae in clinical practice by using boronic acid compounds. Journal of Antimicrobial Chemotherapy. 2010;65(7):1319-1321.
Josa MD, Leal R, Rojas J, Torres MI, Cortés-Muñoz F, Esparza G, Reyes LF. Comparative Evaluation of Phenotypic Synergy Tests versus RESIST-4 O.K.N.V. and NG Test Carba 5 Lateral Flow Immunoassays for the Detection and Differentiation of Carbapenemases in Enterobacterales and Pseudomonas aeruginosa. Microbiology Spectrum. 2022;10(1):e01080-21..
Cordeiro-Moura JR, Fehlberg LCC, Nodari CS et al. Performance of distinct phenotypic methods for carbapenemase detection: The influence of culture media. Diagnostic Microbiology and Infectious Disease. 2020;96(3): 114912.
Li J, Li C, Cai X et al. Performance of modified carbapenem inactivation method and inhibitor-based combined disk test in the detection and distinguishing of carbapenemase producing Enterobacteriaceae. Annals of Translational Medicine. 2019;7(20):566.
Noubam-Tchatat CC, Maurin E, Proust S, Beyrouthy R, Bonnet R, Robin F. MAST® D72C test: a novel option for ESBL, AmpC and carbapenemase detection. European Journal of Clinical Microbiology & Infectious Diseases. 2024;43, 1181–1192.
Solgi H, Badamchi A, Shahcheraghi F, Badmasti F, Akbari M, Behzadfar M. A comparative evaluation of five phenotypic methods for identification of carbapenemase-producing Enterobacteriaceae: a modified carbapenemase detection test. Microbiology Spectrum. 2024;12(7):e00386-24.
AbdelGhani S, Thomson GK, Snyder JW, Thomson KS. Comparison of the Carba NP, Modified Carba NP, and Updated Rosco Neo-Rapid Carb Kit Tests for Carbapenemase Detection. Journal of Clinical Microbiology. 2015;53(11):3539-3542.
Referanslar
Hrabak J, Chudáčková E, Papagiannitsis CC. Detection of carbapenemases in Enterobacteriaceae: a challenge for diagnostic microbiological laboratories. Clinical Microbiology and Infection. 2014;20(9): 839-853.
Tamma P D, Simner PJ. Phenotypic Detection of Carbapenemase-Producing Organisms from Clinical Isolates. Journal of Clinical Microbiology. 2018;56(11): e01140-18.
Bartolini A, Frasson I, Cavallaro A, Richter SN, Palù G. Comparison of phenotypic methods for the detection of carbapenem non-susceptible Enterobacteriaceae. Gut Pathogens. 2014;6(1), 13.
Pournaras S, Poulou A, Tsakris A. Inhibitor-based methods for the detection of KPC carbapenemase-producing Enterobacteriaceae in clinical practice by using boronic acid compounds. Journal of Antimicrobial Chemotherapy. 2010;65(7):1319-1321.
Josa MD, Leal R, Rojas J, Torres MI, Cortés-Muñoz F, Esparza G, Reyes LF. Comparative Evaluation of Phenotypic Synergy Tests versus RESIST-4 O.K.N.V. and NG Test Carba 5 Lateral Flow Immunoassays for the Detection and Differentiation of Carbapenemases in Enterobacterales and Pseudomonas aeruginosa. Microbiology Spectrum. 2022;10(1):e01080-21..
Cordeiro-Moura JR, Fehlberg LCC, Nodari CS et al. Performance of distinct phenotypic methods for carbapenemase detection: The influence of culture media. Diagnostic Microbiology and Infectious Disease. 2020;96(3): 114912.
Li J, Li C, Cai X et al. Performance of modified carbapenem inactivation method and inhibitor-based combined disk test in the detection and distinguishing of carbapenemase producing Enterobacteriaceae. Annals of Translational Medicine. 2019;7(20):566.
Noubam-Tchatat CC, Maurin E, Proust S, Beyrouthy R, Bonnet R, Robin F. MAST® D72C test: a novel option for ESBL, AmpC and carbapenemase detection. European Journal of Clinical Microbiology & Infectious Diseases. 2024;43, 1181–1192.
Solgi H, Badamchi A, Shahcheraghi F, Badmasti F, Akbari M, Behzadfar M. A comparative evaluation of five phenotypic methods for identification of carbapenemase-producing Enterobacteriaceae: a modified carbapenemase detection test. Microbiology Spectrum. 2024;12(7):e00386-24.
AbdelGhani S, Thomson GK, Snyder JW, Thomson KS. Comparison of the Carba NP, Modified Carba NP, and Updated Rosco Neo-Rapid Carb Kit Tests for Carbapenemase Detection. Journal of Clinical Microbiology. 2015;53(11):3539-3542.
