Karbapenem dirençli Pseudomonas ve Acinetobacter türlerinde metallo-beta-laktamaz üretiminin saptanması ve risk faktörlerinin değerlendirilmesi

Abstract

Amaç: Pseudomonas ve Acinetobacter türlerinde, E-test ile MBL sıklığının araştırılması, risk faktörlerinin belirlenmesi ve enfekte hastaların demografik ve klinik özelliklerini değerlendirilmesi.
Materyal ve metod: Çeşitli klinik örneklerden konvansiyonel yöntemlerle izole edilen Pseudomonas ve Acinetobacter türlerinin imipenem veya meropenem direnci imipenem EDTA E-test ile değerlendirildilerek, Metallo-beta-laktamaz (MBL) varlığı incelendi. MBL varlığı saptanan izolatlardan örnekler alınarak, PCR testi ile VIM-1, VIM-2, IMP-1 ve IMP-2 taraması yapıldı.
Bulgular: 46 karbapenem dirençli Acinetobacter spp. izolatından 41'i (%89) ve 19 karbapenem dirençli Pseudomonas spp. izolatından 5'inde (%26) imipenem-EDTA E-testi ile MBL- pozitifliği saptandı. Yoğun bakımda yatış öyküsü, mekanik ventilasyon ve sefalosporin kullanımı MBL üretimi açısından önemli risk faktörleri olarak bulundu.
Sonuç: Özellikle yoğun bakım üniteleri hastalarından izole edilen Acinetobacter ve Pseudomonas türlerinde MBL üretiminin pratik yöntemlerle kısa sürede saptanması, enfeksiyonların hızlı ve etkin bir şekilde kontrol altına alınmasını kolaylaştırarak, salgınların önlenmesinde büyük önem taşımaktadır. 

Keywords

• Metallo-beta-laktamazlar
• Acinetobacter spp
• Pseudomonas spp

Evaluation of risk factors and detection of metallo-beta-lactamase enzyme production in carbapenem-resistant Pseudomonas and Acinetobacter species

Abstract

Purpose: To investigate the frequency of MBLs in Pseudomonas and Acinetobacter species with E-test, to determine the risk factors and to evaluate the demographic and clinical features of infected patients.
Materials and methods: Imipenem or meropenem resistance of Pseudomonas and Acinetobacter isolated from several clinical samples with conventional methods were evaluated with imipenem EDTA E-test and the presence of Metallo-β-lactameses MBL was examined. Several isolates were screened for VIM-1, VIM-2, IMP-1, and IMP-2 with a PCR test.
Results: Of 46 carbapenem resistant Acinetobacter isolates, 41 (89%), as well as of 19 carbapenem resistant Pseudomonas isolates, 5 (26%) had MBL positivity with imipenem-EDTA E-test. A history of Intensive Care Unit stay, mechanical ventilation and cephalosporin use were found to be significant risk factors with respect to MBL production.
Conclusion: Detection of MBL production in Acinetobacter and Pseudomonas species especially in ICU patients is of prime importance to control infection rapidly and effectively, which contribute to prevention of outbreaks. 

Keywords

• Metallo-beta-lactameses
• Acinetobacter spp
• Pseudomonas spp

References

1. Resources 1. Chhatwal P, Ebadi E, Schwab F, et al. Epidemiology and infection control of carbapenem resistant Acinetobacter baumannii and Klebsiella pneumoniae at a German university hospital: a retrospective study of 5 years (2015-2019). BMC Infect Dis. 2021 Nov 27;21(1):1196. doi: 10.1186/s12879-021-06900-3 PMID: 34837973; PMCID: PMC8627082.
2. 2. Zarrilli R, Bagattini M, Migliaccio A, Esposito EP, Triassi M. Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in Italy. Ann Ig. 2021 Sep-Oct;33(5):401-409. doi: 10.7416/ai.2020.2395 Epub 2020 Dec 4. PMID: 33270079.
3. 3. Ling, W., Furuya-Kanamori, L., Ezure, Y., Harris, P., & Paterson, D. L. (2021). Adverse clinical outcomes associated with carbapenem-resistant Acinetobacter (CRA) infections: a systematic review and meta-analysis. JAC-antimicrobial resistance, 3(4), dlab157. https://doi.org/10.1093/jacamr/dlab157
4. 4. David L. Paterson. The Epidemiological Profile of Infections with Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter Species, Clinical Infectious Diseases, Volume 43, Issue Supplement_2, September 2006, Pages S43–S48, https://doi.org/10.1086/504476
5. 5. Ferreira, K. M. Rodrigues, A. C. D. S., Watanabe, A. C., Ferreira, Y. M., & Chang, M. R. (2017). First case of infection by metallo-β-lactamase-producing Pseudomonas aeruginosa in Mato Grosso do Sul, Brazil. Brazilian Journal of Infectious Diseases, 21, 359-360. http://dx.doi.org/10.1016/j.bjid.2016.12.005
6. 6.Yong D, Lee K, Yum JH, et al. Imipenem-EDTA Disk Method for Differentiation of Metallo-ß-Lactamase- Producing Clinical Isolates of Pseudomonas spp. and Acinetobacter spp. Journal of Clinical Microbiology.2002 Oct; 40 (10): 3798-3801. https://doi.org/10.1128/JCM.40.10.3798-3801.2002
7. 7. Pitout JDD, Gregson DB, Poirel L, et al. Detection of Pseudomonas aeruginosa Producing Metallo-ß-Lactamases in a Large centralized Laboratory. Journal of Clinical Microbiology 2005 July; 43 (7): 3129-3135.https://doi.org/10.1128/JCM.43.7.3129-3135.2005
8. 8. Doi Y. Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections. Clin Infect Dis. 2019 Nov 13;69(Suppl 7):S565-S575. doi: 10.1093/cid/ciz830. PMID: 31724043; PMCID: PMC6853760.

9. 9. Nordmann P, Poirel L. Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria. Clin Infect Dis. 2019 Nov 13;69(Suppl 7):S521-S528. doi: 10.1093/cid/ciz824. PMID: 31724045; PMCID: PMC6853758. 10.Brink AJ. Epidemiology of carbapenem-resistant Gram-negative infections globally. Curr Opin Infect Dis. 2019 Dec;32(6):609-616. doi: 10.1097/QCO.0000000000000608. PMID: 31567571.
10. 11.Shortridge D, Gales AC, Streit JM, Huband MD, Tsakris A, Jones RN. Geographic and Temporal Patterns of Antimicrobial Resistance in Pseudomonas aeruginosa Over 20 Years From the SENTRY Antimicrobial Surveillance Program, 1997-2016. Open Forum Infect Dis. 2019 Mar 15;6(Suppl 1):S63-S68. doi: 10.1093/ofid/ofy343. PMID: 30895216; PMCID: PMC6419917.
11. 12. Gales, A. C., Seifert, H., Gur, D., Castanheira, M., Jones, R. N., & Sader, H. S. (2019). Antimicrobial Susceptibility of Acinetobacter calcoaceticus-Acinetobacter baumannii Complex and Stenotrophomonas maltophilia Clinical Isolates: Results From the SENTRY Antimicrobial Surveillance Program (1997-2016). Open forum infectious diseases, 6(Suppl 1), S34–S46. https://doi.org/10.1093/ofid/ofy293
12. 13. John E, McGowan J. Resistance in nonfermenting gram-negative bacteria: Multidrug resistance to the maximum Am J Infect Control 2006 June; 34 (5) Suppl. 1: S29-37. https://doi.org/10.1016/j.ajic.2006.05.226
13. 14. Giske GC, Monnet DL, Cars O, et al. Clinical and Economic Impact of Common Multidrug-Resistant Gram-negative Bacilli. Antimicrobial Agents and Chemotherapy 2008 Mar; 52 (3): 813-821. https://doi.org/10.1128/AAC.01169-07
14. 15. Rostami S, Farajzadeh Sheikh A, Shoja S, Farahani A, Tabatabaiefar MA, Jolodar A, Sheikhi R. Investigating of four main carbapenem-resistance mechanisms in high-level carbapenem resistant Pseudomonas aeruginosa isolated from burn patients. J Chin Med Assoc. 2018 Feb;81(2):127-132. doi: 10.1016/j.jcma.2017.08.016. Epub 2017 Oct 9. PMID: 29033110.
15. 16. Cornaglia G, Akova M, Amicosante G, et al. Metallo-ß-lactamases as emerging resistance determinants in Gram- negative pathogens: open issues. International Journal of Antimicrobial Agents 2007 Apr, 29 (4): 380-388. https://doi.org/10.1016/j.ijantimicag.2006.10.008
16. 17. Thomas R. F., Sader H. S., Toleman A., et al. Emerging Metallo-ß-lactamase-Mediated Resistances: A Summary Report from the Worldwide SENTRY Antimicrobial Surveillance Program. Clinical Infectious Diseases 2005 Aug; 15; 41 Suppl 4: S276-278. https://doi.org/10.1086/430790
17. 18. Yan JJ, Wu JJ, Tsai SH, Chuang CL. Comparison of the double-disk, combined disk, and E-test methods for detecting metallo-ß-lactamases in gram-negative bacilli. Diagnostic Microbiology and Infectious Disease 2004 May; 49 (1): 5-11. https://doi.org/10.1016/j.diagmicrobio.2004.01.002
18. 19. Moulana Z, Babazadeh A, Eslamdost Z, Shokri M, Ebrahimpour S. Phenotypic and genotypic detection of metallo-beta-lactamases in Carbapenem resistant Acinetobacter baumannii. Caspian J Intern Med. 2020;11(2):171-176. doi: 10.22088/cjim.11.2.171. PMID: 32509245; PMCID: PMC7265521.
19. 20. Massik A, Hibaoui L, Arhoune B, Yahyaoui G, Oumokhtar B, Mahmoud M. Detection of metallo-beta lactamases and oxacillinase genes in carbapenem-resistant Acinetobacter baumannii strains isolated in Morocco. Pan Afr Med J. 2021 Dec 7;40:210. doi: 10.11604/pamj.2021.40.210.28663. PMID: 35136473; PMCID: PMC8783299.
20. 21. Arakawa Y, Shibata N, Shibayama K., et al. Convenient Test for Screenin Metallo-ß-lactamase-Producing Gram-Negative Bacteria by Using Thiol Compounds. Journal Of Clinical Microbiology, 2000 Jan; 38 (1): 40-43. https://doi.org/10.1128/JCM.38.1.40-43.2000
21. 22. Vural, E., Delialioğlu, N., Ulger, S. T., Emekdas, G., & Serin, M. S. (2020). Phenotypic and molecular detection of the metallo-Beta-lactamases in carbapenem-resistant Pseudomonas aeruginosa isolates from clinical samples. Jundishapur Journal of Microbiology, 13(2). doi: 10.5812/jjm. 90034
22. 23. Walsh TR, Bolmström A, Qwarnström A; Gales A, et al. Evaluation of New Etest for Detecting Metallo-ß-lactamases in Routine Clinical Testing. Journal of Clinical Microbiology. 2002 Aug; 40 (8): 2755-2759. https://doi.org/10.1128/JCM.40.8.2755-2759.2002
23. 24. Samuelsen Ø, Buarø .L, Giske CG, et al. Evaluation of phenotyphic tests for the detection of metallo ß-lactamase-producing Pseudomonas aeruginosa in low prevalance country. Journal of Antimicrobial Chemotherapy. 2008 Jan; 61 (4): 827-830. https://doi.org/10.1093/jac/dkn016
24. 25. Bayraktar B, Yıldız D, Bulut E. Investigation of Metallo beta-lactamase Production in Carbapenem resistant Pseudomonas aeruginosa Strains Isolated in Intensive Care Unit. Journal of Turkish Society of Microbiology.2004; 34: 248-252. 26. Aksoy, M. D., Çavuşlu, Ş., & Tuğrul, H. M. (2015). Investigation of metallo beta lactamases and oxacilinases in carbapenem resistant Acinetobacter baumannii strains isolated from inpatients. Balkan medical journal, 32(1), 79-83. DOI: 10.5152/balkanmedj.2015.1530
25. 27. Aktaş Z, Kayacan ÇB. Investigation of metallo-beta-lactamase producing strains of Pseodomonas aeruginosa and Acinetobacter baumannii by E-test, disk synergy and PCR. Scandinavian Journal of Infectious Diseases. 2008;40 (4): 320-325. https://doi.org/10.1080/00365540701704698
26. 28. Chu YW, Cheung TKM, Ngan KM, Kam KM. EDTA susceptibility leading to false detection of metallo- ß-lactamase in Pseudomonas aeruginosa by Etest and an imipenem–EDTA disk method. Letters to the Editor. International Journal of Antimicrobial Agents 2005 Oct; 26 (4): 340-341.
27. 29. Berges L, Villalobos HR, Deplano A, Struelens MJ. Prospective evaluation of imipenem/EDTA combined disc and Etest for detection of metallo-ß-lactamase-producing Pseudomonas aeruginosa. Journal of Antimicrobial Chemotheray 2007; Apr; 59 (4): 812-813. https://doi.org/10.1093/jac/dkm001
28. 30. Tam VH, Chang KT, LaRocco MT, et al. Prevalance, mechanism, and risk factors of carbapenem resistance in bloodstream isolates of Pseudomonas aeruginosa. Diagnostic Microbiology and Infectious Disease 2007 Jul; 58 (3): 309-314. https://doi.org/10.1016/j.diagmicrobio.2007.05.006
29. 31. Hirakata Y, Yamaguchi T, Nakano M, et al. Clinical and Bacteriological Characteristics of IMP-Type Metallo-ß-lactamase-Producing Pseudomonas aeruginosa. Clin Infect Dis 2003 Jul; 1;37 (1): 26-32. https://doi.org/10.1086/375594
30. 32. Marra AR, Pereira CA, Gales AC, Menezes LC. Bloodstream Infections with Metallo-ß-Lactamase-Producing Pseudomonas aeruginosa: Epidemiology, Microbiology, and Clinical Outcomes. Antimicrob Agents Chemother. 2006 Jan; 50 (1): 388-390. https://doi.org/10.1128/AAC.50.1.388-390.2006
31. 33. Deeba, B., Manzoor, A. T., Bashir, A. F., Gulnaz, B., Danish, Z., Shabir, A., & Abubaker, S. T. (2011). Detection of metallo-beta-lactamase (MBL) producing Pseudomonas aeruginosa at a tertiary care hospital in Kashmir. African Journal of Microbiology Research, 5(2), 164-172. DOI: 10.5897/AJMR10.694
32. 34. Nakano T, Hiramatsu K, Hirata N, et al. Clinical characterization of blaIMP positive gram-negative rods isolated cases..Kansenshogaku Zasshi 2001 Nov; 75 (11): 946-954 DOI: 10.11150/kansenshogakuzasshi1970.75.946 PMID: 11766377
33. 35. Abbo A, Navon-Venezia S, Hammer-Muntz O, et al. Multidrug-resistant Acinetobacter baumannii. Emerging Infectious Diseases 2005 Jan; 11(1): 22-29.
34. 36. Laupland KB, Parkins MD, Church DL, et al. Population-based epidemiological study of infections caused by carbapenem-resistant Pseudomonas aeruginosa in the Calgary Health Region: importance of metallo-beta-lactamase (MBL)-producing strains. J Infect Dis. 2005 Nov; 1;192 (9): 1606-12. https://doi.org/10.1086/444469