Çeşitli Klinik Örneklerden İzole Edilen Pseudomonas aeruginosa'nın Karbapenemaz Üretimi ve Tiplendirilmesinde Fenotipik ve Genotipik Yöntemlerin Değerlendirilmesi
Year 2024,
Volume: 4 Issue: 2, 42 - 49, 30.05.2024
Hatice Karali
,
Mehmet Mücahit Güncü
,
Mehmet Burak Aksu
Abstract
Amaç: Son on yılda karbapenem dirençli Pseudomonas aeruginosa izolatlarının artışı enfeksiyon tedavisinde önemli bir sağlık sorunu haline gelmiştir. Rutin laboratuvarda karbapenem direncinin saptanması için gereken süre yaklaşık 48 saattir. Bu durum, özellikle kritik hastalarda etkili tedavinin başlatılmasında gecikmeye neden olur. Bu nedenle çalışmalar antimikrobiyal direncin daha erken tespit edilmesi için yeni yöntemlere odaklanmaktadır. Bu çalışmada, karbapenem dirençli P. aeruginosa izolatlarında karbapenemaz üretimine bağlı direncin fenotipik ve genotipik yöntemlerle araştırılması amaçlanmıştır.
Yöntemler: Marmara Üniversitesi Pendik Eğitim ve Araştırma Hastanesi Mikrobiyoloji Laboratuvarı’nda Ocak 2018 ile Şubat 2023 tarihleri arasında çeşitli klinik örneklerden izole edilen 120 P. aeruginosa izolatı rutin antibiyogram sonuçlarına bakılarak çalışmamıza dahil edilmiştir. Karbapenemaz üretimi fenotipik test olarak enzim-substrat etkileşimine dayalı reaksiyon temelli kolormatik yöntem ve genotipik test olarak polimeraz zincir reaksiyonu ile tespit edilmiştir.
Bulgular: Bu çalışmada karbapenem dirençli 100 izolatın 46'sında (%46) genotipik yöntemle karbapenemaz kodlayan genler tespit edilmiştir. Fenotipik test ile karbapenemaz enzimi taşıyan 46 izolatın 31’inde (%67) 1 saat içinde pozitif sonuçlar kaydedilmiştir. Geriye kalan 13 izolat yanlış negatif olarak; moleküler yöntem ile direnç genlerini taşımadığı belirlenen 2 izolat ise yanlış pozitif olarak değerlendirilmiştir. Fenotipik testin duyarlılık ve özgüllüğü sırasıyla; %67.4 ve %97.3 (p<0.0001) olarak bulunmuştur.
Sonuç: Sonuç olarak, karbapenem dirençli P. aeruginosa izolatlarının hızlı ve doğru tanımlanması, zamanında uygun tedavinin verilmesi ve enfeksiyon kontrol önlemlerinin başarılı bir şekilde uygulanması açısından oldukça önemlidir. Çalışmamızda kullandığımız enzim-substrat etkileşimine dayalı reaksiyon temelli kolormatik testin performansının değerlendirilebilmesi için daha fazla örnek içeren in vitro çalışmalara ihtiyaç vardır.
Ethical Statement
Bu çalışma, Marmara Üniversitesi Tıp Fakültesi Klinik Araştırmalar Etik Kurulu tarafından (03.02.2023 tarih ve 265 kayıt numarası) onaylanmıştır.
Supporting Institution
Marmara Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi (BAPKO)
Project Number
TYL-2023-11039
References
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- 24. Osei SJ, Govinden U, Essack SY. Review of established and innovative detection methods for carbapenemase‐producing Gram‐negative bacteria. Journal of Applied Microbiology, 2015;119 (5): 1219-1233.
- 25. Perry JD, Naqvi SH, Mirza IA., Alizai SA, Hussain A, Ghirardi S & Raza MW. Prevalence of faecal carriage of Enterobacteriaceae with NDM-1 carbapenemase at military hospitals in Pakistan and evaluation of two chromogenic media. Journal of Antimicrobial Chemotherapy. 2011;66(10): 2288-2294.
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- 29. Rizek C, Fu L, Dos Santos LC, Leite G, Ramos J, Rossi F, & Costa SF. Characterization of carbapenem-resistant Pseudomonas aeruginosa clinical isolates, carrying multiple genes coding for this antibiotic resistance. Annals of Clinical Microbiology and Antimicrobials. 2014; 13: 1-5.
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- 31. Shaaban M, Al-Qahtani A, Al-Ahdal M, Barwa R. Molecular characterization of resistance mechanisms in Pseudomonas aeruginosa isolates resistant to carbapenems. The Journal of Infection in Developing Countries. 2017; 11(12): 935-943.
- 32. Simner PJ, Johnson JK, Brasso WB, Anderson K, Lonsway DR, Pierce VM & Roe-Carpenter DE. Multicenter evaluation of the modified carbapenem inactivation method and the Carba NP for detection of carbapenemase-producing Pseudomonas aeruginosa and Acinetobacter baumannii. Journal of Clinical Microbiology. 2018);56(1): 10-1128.
- 33. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL& Zorzet A. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet İnfectious Diseases. 2018;18(3): 318-327.
- 34. Tamma PD, Opene BN, Gluck A, Chambers KK, Carroll KC, & Simner PJ. Comparison of 11 phenotypic assays for accurate detection of carbapenemase-producing Enterobacteriaceae. Journal of Clinical Microbiology. 2017; 55(4): 1046-1055.
- 35. The European Committee on Antimicrobial Susceptibility Testing. EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance. 2017.
- 36. Thomson G, Turner D, Brasso W, Kircher S, Guillet T, Thomson K. High-stringency evaluation of the automated BD Phoenix CPO detect and Rapidec Carba NP tests for detection and classification of carbapenemases. Journal of Clinical Microbiology. 2017;55(12): 3437-3443.
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- 38. Tijet N, Boyd D, Patel SN, Mulvey MR, Melano RG. Evaluation of the Carba NP test for rapid detection of carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy. 2013;57(9): 4578-4580.
- 39. Walsh, TR, Toleman MA, Poirel L, Nordmann P. Metallo-β-lactamases: the quiet before the storm? Clinical Microbiology Reviews, 2005;18(2): 306-325.
- 40. Yusuf E, Van Der Meeren S, Schallier A, Piérard D. Comparison of the Carba NP test with the Rapid CARB Screen Kit for the detection of carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa. European Journal of Clinical Microbiology & İnfectious Diseases, 2014; 33: 2237-2240.
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Evaluation of Phenotypİc and Genotypic Methods for Carbapenemase Production and Typing In Pseudomonas aeruginosa Isolates from Various Clinical Samples
Year 2024,
Volume: 4 Issue: 2, 42 - 49, 30.05.2024
Hatice Karali
,
Mehmet Mücahit Güncü
,
Mehmet Burak Aksu
Abstract
Objective: The increase in carbapenem-resistant Pseudomonas aeruginosa isolates has become an important health problem in infection treatment in the last decade. The time required to detect carbapenem resistance in the routine laboratory setting is about 48 hours. So, it causes a delay in the initiation of effective treatment, especially in critically ill patients. For this reason, studies focus on new methods to detect antimicrobial resistance earlier. It aimed to investigate carbapenemase-dependent resistance by phenotypic and genotypic methods in carbapenem-resistant clinical P. aeruginosa isolates in this study.
Methods: A hundred twenty P. aeruginosa isolates obtained from clinical samples between January 2018 to February 2023 in the Microbiology Laboratory of Marmara University Pendik Training and Research Hospital, were included in our study based on routine antibiogram results. Carbapenemase production was detected by enzyme-substrate reaction-based colorimetric method as a phenotypic test and polymerase chain reaction as a genotypic test.
Results: In this study, carbapenemase-coding genes were detected in 46 (46%) of 100 carbapenem-resistant isolates by genotypic method. With the phenotypic test, positive results were recorded within 1 hour in 31 of 46 isolates (67%) carrying the carbapenemase enzyme. The remaining 13 isolates were false negatives; 2 isolates determined not to carry the resistance genes by molecular method were evaluated as false positives. The sensitivity and specificity of the phenotypic test were 67.4% and 97.3%, respectively (p<0.0001).
Conclusion: In conclusion, rapid and accurate identification of carbapenem-resistant P. aeruginosa isolates is very important for the timely administration of appropriate treatment and successful implementation of infection control measures. In vitro studies with a larger number of samples are needed to evaluate the performance of the enzyme-substrate reaction-based colorimetric test that we used in our study.
Project Number
TYL-2023-11039
References
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- 2. Aguirre-Quiñonero A & Martínez-Martínez L. Non-molecular detection of carbapenemases in Enterobacteriaceae clinical isolates. Journal of Infection and Chemotherapy. 2017; 23(1):1-11.
- 3. Akhi MT, Khalili Y, Ghotaslou R, Kafil HS, Yousefi S, Nagili B & Goli HR. Carbapenem inactivation: a very affordable and highly specific method for phenotypic detection of carbapenemase-producing Pseudomonas aeruginosa isolates compared with other methods. Journal of Chemotherapy. 2017; 29(3):144-149.
- 4. Aktaş E, Malkoçoğlu G, Otlu B, Çopur ÇA, Külah C, Cömert F, & Bulut ME. Evaluation of the carbapenem inactivation method for detection of carbapenemase-producing gram-negative bacteria in comparison with the rapıdec carba np. Microbial Drug Resistance. 2017;23 (4): 457-461.
- 5. Aktaş Z, Kayacan ÇB, Schneider I, Can B, Midilli K, Bauernfeind A. Carbapenem-hydrolyzing oxacillinase, OXA-48, persists in Klebsiella pneumoniae in Istanbul, Turkey. Chemotherapy. 2008; 54(2): 101-106.
- 6. Bayramoğlu G, Ulucam G, Gençoğlu ÖÇ, Kılıç A, Aydin F. Comparison of the modified hodge test and the carba NP test for detection of carbapenemases in enterobacteriaceae isolates enterobacteriaceae izolatlarinda karbapenemazlarin saptanmasinda modifiye hodge testi ve carba NP testlerinin karşilaştirilmasi. Mikrobiyoloji Bulteni, 2016;50(1):1-10.
- 7. Castanheira M, Deshpande LM, Costello A, Davies TA, Jones RN. Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009–11 in 14 European and Mediterranean countries. Journal Of Antimicrobial Chemotherapy. 2014; 69(7):1804-1814.
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- 9. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth informational supplement M100-S25. CLSI, Wayne, PA. 2015.
- 10. Çelik N. Çoğul dirençli nozokomiyal pseudomonas aeruginosa suşlarında beta laktamazların fenotipik ve genotipik olarak incelenmesi.2007.
- 11. Çopur ÇA, Ertürk A, Ejder N, Rakici E, Kostakoğlu U, Esen Yİ, Sönmez E. Screening of antimicrobial resistance genes and epidemiological features in hospital and community-associated carbapenem-resistant pseudomonas aeruginosa infections. Infection and Drug Resistance. 2021; 14: 1517-1526.
- 12. Dortet L, Bréchard L, Cuzon G, Poirel L, Nordmann P. Strategy for rapid detection of carbapenemase-producing Enterobacteriaceae. Antimicrobial Agents And Chemotherapy, 2014; 58(4): 2441-2445.
- 13. Dortet L, Poirel L, Errera C, Nordmann P. CarbAcineto NP test for rapid detection of carbapenemase-producing acinetobacter spp. Journal off Clinical Microbiology. 2014; 52(7): 2359-2364.
- 14. ECDC, European Centre for Disease Prevention and Control, Surveillance Report Antimicrobial Resistance İn The Eu/Eea (Ears-Net) ,2022.
- 15. Halat DH, Moubareck CA. The intriguing carbapenemases of Pseudomonas aeruginosa: current status, genetic profile, and global epidemiology. The Yale Journal of Biology and Medicine, 2022; 95(4): 507.
- 16. Henry DA, Speert DP. Pseudomonas. in: Versalovic J, Carroll KC, Jorgensen JH, Funke G, Landry ML, Warnock DW (eds), Manual of Clinical Microbiology. 2011;Vol.1. (10th ed) Washington DC, s: 677-691.
- 17. Jean, SS, Harnod D, Hsueh PR. Global threat of carbapenem-resistant Gram-negative bacteria. Frontiers in Cellular and İnfection Microbiology. 2022; 12: 823684.
- 18. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE., Sharma S,& Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical Care Medicine. 2006; 34(6): 1589-1596.
- 19. Malkoçoğlu G, Aktaş E, Bayraktar B, Otlu B, Bulut ME. VIM-1, VIM-2, and GES-5 carbapenemases among Pseudomonas aeruginosa isolates at a tertiary hospital in Istanbul, Turkey. Microbial Drug Resistance. 2017; 23(3): 328-334.
- 20. Mangayarkarasi V, Moses SP, Swarna SR, Kalaiselvi K, Fathima SS. In-house standardization of Carba NP test for carbapenemase detection in gram negative bacteria. Int J Curr Microbiol Appl Sci, 2018; 7(01): 2876-2881.
- 21. Nordmann, P. Carbapenemase-producing Enterobacteriaceae: overview of a major public health challenge. Medecine et Maladies İnfectieuses. 2014; 44(2): 51-56.
- 22. Nordmann P, Poirel L. Strategies for identification of carbapenemase-producing Enterobacteriaceae. Journal of Antimicrobial Chemotherapy. 2013); 68(3): 487-489.
- 23. Nordmann P, Poirel L, Dortet L. Rapid detection of carbapenemase-producing Enterobacteriaceae. Emerging İnfectious Diseases. 2012; 18(9): 1503.
- 24. Osei SJ, Govinden U, Essack SY. Review of established and innovative detection methods for carbapenemase‐producing Gram‐negative bacteria. Journal of Applied Microbiology, 2015;119 (5): 1219-1233.
- 25. Perry JD, Naqvi SH, Mirza IA., Alizai SA, Hussain A, Ghirardi S & Raza MW. Prevalence of faecal carriage of Enterobacteriaceae with NDM-1 carbapenemase at military hospitals in Pakistan and evaluation of two chromogenic media. Journal of Antimicrobial Chemotherapy. 2011;66(10): 2288-2294.
- 26. Pitout JD, Gregson DB, Poirel L, McClure JA, Le P, Church DL. Detection of Pseudomonas aeruginosa producing metallo-β-lactamases in a large centralized laboratory. Journal Of Clinical Microbiology. 2005; 43(7): 3129-3135.
- 27. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagnostic Microbiology and Infectious Disease, 2011; 70(1): 119–123.
- 28. Potron A, Poirel L, Nordmann P. Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: mechanisms and epidemiology. International Journal Of Antimicrobial Agents. 2015; 45(6): 568-585.
- 29. Rizek C, Fu L, Dos Santos LC, Leite G, Ramos J, Rossi F, & Costa SF. Characterization of carbapenem-resistant Pseudomonas aeruginosa clinical isolates, carrying multiple genes coding for this antibiotic resistance. Annals of Clinical Microbiology and Antimicrobials. 2014; 13: 1-5.
- 30. Rudresh SM, Ravi GS, Sunitha L, Hajira SN, Kalaiarasan E, Harish BN. Simple, rapid, and cost-effective modified Carba NP test for carbapenemase detection among Gram-negative bacteria. Journal of Laboratory Physicians. 2017; 9(04): 303-307.
- 31. Shaaban M, Al-Qahtani A, Al-Ahdal M, Barwa R. Molecular characterization of resistance mechanisms in Pseudomonas aeruginosa isolates resistant to carbapenems. The Journal of Infection in Developing Countries. 2017; 11(12): 935-943.
- 32. Simner PJ, Johnson JK, Brasso WB, Anderson K, Lonsway DR, Pierce VM & Roe-Carpenter DE. Multicenter evaluation of the modified carbapenem inactivation method and the Carba NP for detection of carbapenemase-producing Pseudomonas aeruginosa and Acinetobacter baumannii. Journal of Clinical Microbiology. 2018);56(1): 10-1128.
- 33. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL& Zorzet A. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet İnfectious Diseases. 2018;18(3): 318-327.
- 34. Tamma PD, Opene BN, Gluck A, Chambers KK, Carroll KC, & Simner PJ. Comparison of 11 phenotypic assays for accurate detection of carbapenemase-producing Enterobacteriaceae. Journal of Clinical Microbiology. 2017; 55(4): 1046-1055.
- 35. The European Committee on Antimicrobial Susceptibility Testing. EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance. 2017.
- 36. Thomson G, Turner D, Brasso W, Kircher S, Guillet T, Thomson K. High-stringency evaluation of the automated BD Phoenix CPO detect and Rapidec Carba NP tests for detection and classification of carbapenemases. Journal of Clinical Microbiology. 2017;55(12): 3437-3443.
- 37. Tijet N, Boyd D, Patel SN, Mulvey MR, Melano RG. Reply to “further proofs of concept for the Carba NP test.” Antimicrob Agents Chemother. 2014; 58:1270.
- 38. Tijet N, Boyd D, Patel SN, Mulvey MR, Melano RG. Evaluation of the Carba NP test for rapid detection of carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy. 2013;57(9): 4578-4580.
- 39. Walsh, TR, Toleman MA, Poirel L, Nordmann P. Metallo-β-lactamases: the quiet before the storm? Clinical Microbiology Reviews, 2005;18(2): 306-325.
- 40. Yusuf E, Van Der Meeren S, Schallier A, Piérard D. Comparison of the Carba NP test with the Rapid CARB Screen Kit for the detection of carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa. European Journal of Clinical Microbiology & İnfectious Diseases, 2014; 33: 2237-2240.
- 41. Zhang Y, Chen XL, Huang AW, Liu SL, Liu WJ, Zhang N, Lu XZ. Mortality attributable to carbapenem-resistant Pseudomonas aeruginosa bacteremia: a meta-analysis of cohort studies. Emerging Microbes & İnfections, 2016;5(1): 1-6.