IN VITRO ACTIVITY OF CEFTAZIDIME-AVIBACTAM AND COLISTIN AGAINST CARBAPENEM-RESISTANT PSEUDOMONAS AERUGINOSA CLINICAL ISOLATES

Öz

Objective: Infections caused by multi drug-resistant Gram-neg- ative bacilli are increasingly reported worldwide. Ceftazi- dime-avibactam is a novel antibiotic combination that presents good activity against carbapenem-resistant Enterobacterales members and Pseudomonas aeruginosa isolates. The objec- tive of this study was to evaluate the in vitro activity of ceftazi- dime-avibactam and colistin against carbapenem-resistant P. aeruginosa isolates.
Materials and Methods: A total of 100 carbapenem-resistant and non-duplicate P. aeruginosa isolates obtained from patient samples in our hospital between 2016-2021 were included in the study. The isolates were identified by MALDI-TOF MS (Bruker Daltonics, Germany). The minimum inhibitory concentration (MIC) values of meropenem, colistin, ceftazidime, and ceftazi- dime-avibactam were determined by the broth microdilution method. The presence of carbapenemase genes bla KPC, bla NDM, bla OXA-48, bla IMP, and bla VIM were investigated using PCR.
Results: Carbapenemase genes were not detected among the isolates except for one isolate producing bla VIM. The susceptibil- ity rates of ceftazidime-avibactam and colistin were 90% (n=90) and 100% (n=100), respectively. The MIC50 and MIC90 values for meropenem, ceftazidime, ceftazidime-avibactam, and colistin against P. aeruginosa isolates were found to be 32/64, 8/64, 4/8, 0.5/2 μg/mL, respectively.

Anahtar Kelimeler

• Ceftazidime-avibactam
• colistin
• carbapenem
• Pseudomonas aeruginosa

SEFTAZİDİM-AVİBAKTAM VE KOLİSTİNİN KARBAPENEM DİRENÇLİ PSEUDOMONAS AERUGİNOSA KLİNİK İZOLATLARINA KARŞI İN VİTRO AKTİVİTESİ

Öz

Amaç: Çok ilaca dirençli Gram negatif basillerin neden olduğu enfeksiyonlar dünya genelinde giderek daha fazla rapor edilmektedir. Seftazidim-avibaktam, karbapenem dirençli Entero- bacterales üyelerine ve Pseudomonas aeruginosa izolatlarına karşı iyi etkinlik gösteren yeni bir antibiyotik kombinasyonudur. Bu çalışmanın amacı, seftazidim-avibaktam ve kolistinin karbapenem dirençli P. aeruginosa izolatlarına karşı in vitro aktivitesini değerlendirmektir.
Gereç ve Yöntem: Hastanemizde 2016-2021 yılları arasında hasta örneklerinden elde edilen toplam 100 karbapenem dirençli ve tekrar içermeyen P. aeruginosa izolatı çalışmaya dahil edildi. İzo- latlar MALDI-TOF MS (Bruker Daltonics, Almanya) ile tanımlandı. Meropenem, kolistin, seftazidim ve seftazidim-avibaktamın mini- mum inhibitör konsantrasyon (MİK) değerleri sıvı mikrodilüsyon yöntemi ile belirlendi. Karbapenemaz genlerinden bla KPC, bla NDM, bla OXA-48, bla IMP, ve bla VIM varlığı PCR ile araştırıldı.
Bulgular: Bir bla VIM üreten izolat dışında izolatlarda karbapenemaz genleri saptanmadı. Seftazidim-avibaktam ve kolistinin duyarlılık oranları sırasıyla %90 (n=90) ve %100 (n=100) bulundu. P. aeruginosa izolatlarına karşı meropenem, seftazidim, seftazidim-avibaktam ve kolistin için MİK50 ve MİK90 değerleri sırasıyla 32/64, 8/64, 4/8, 0,5/2 μg/mL olarak bulundu.
Sonuç: Verilerimiz seftazidim-avibaktamın karbapenem dirençli P. aeruginosa izolatlarının tedavisi için iyi bir alternatif seçenek olduğunu göstermektedir. Çalışma izolatları arasında kolistin direnci tespit edilmemesi dikkat çekicidir. Antibiyotiklere direnç gelişiminin önlenmesi için akılcı antibiyotik kullanımına önem verilmelidir. Seftazidim-avibaktam ve kolistin sürveyansı rutin anti- mikrobiyal duyarlılık testleri ile takip edilmelidir.

Anahtar Kelimeler

• Seftazidim-avibaktam
• kolistin
• karbapenem
• Pseudomonas aeruginosa

Kaynakça

1. 1. Shrivastava S, Shrivastava P, Ramasamy J. World Health Organization releases global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. J Med Soc 2018;32(1):76-7. [CrossRef] google scholar
2. 2. Mirza HC, Hortaç E, Koçak AA, Demirkaya MH, Yayla B, Güçlü AÜ, et al. In vitro activity of ceftolozane-tazobactam and ceftazidime-avibactam against clinical isolates of meropenem-non-susceptible Pseudomonas aeruginosa: A two-centre study. J Glob Antimicrob Resist 2020;20:334-8. [CrossRef] google scholar
3. 3. Buehrle DJ, Shields RK, Chen L, Hao B, Press EG, Alkrouk A, et al. Evaluation of the in vitro activity of ceftazidime-avibactam and ceftolozane-tazobactam against meropenem-resistant Pseudomonas aeruginosa isolates Antimicrob Agents Chemother 2016;60(5):3227-31. [CrossRef] google scholar
4. 4. Mataraci Kara E, Yilmaz M, İstanbullu Tosun A, Özbek Çelik B. Synergistic activities of ceftazidime-avibactam in combination with different antibiotics against colistin-nonsusceptible clinical strains of Pseudomonas aeruginosa. Infect Dis (Lond) 2020;52(9):616-24. [CrossRef] google scholar
5. 5. Stone GG, Smayevsky J, Kazmierczak K. Longitudinal analysis of the in vitro activity of ceftazidime-avibactam vs. Pseudomonas aeruginosa, 2012-2016. Diagn Microbiol Infect Dis 2020;96(1):114835. [CrossRef] google scholar
6. 6. Soriano A, Carmeli Y, Omrani AS, Moore LSP, Tawadrous M, Irani P. Ceftazidime-avibactam for the treatment of serious Gram-negative infections with limited treatment options: A systematic literature review. Infect Dis Ther 2021;10(4):1989-2034. [CrossRef] google scholar
7. 7. Andrade FF, Silva D, Rodrigues A, Pina-Vaz C. Colistin update on its mechanism of action and resistance, present and future challenges. Microorganisms 2020;8(11):1716. [CrossRef] google scholar
8. 8. Bialvaei AZ, Samadi Kafil H. Colistin, mechanisms and prevalence of resistance. Curr Med Res Opin 2015;31(4):707-21. [CrossRef] google scholar

9. 9. Clinical and Laboratory Standards Institute. 2015. M07-A9. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard, 10th ed. Clinical and Laboratory Standards Institute, Wayne, PA. Available from: https://clsi.org google scholar
10. 10. European Committee on Antimicrobial Susceptibility Testing. 2022. Breakpoint tables for interpretation of MICs and zone diameters. Version 12.0, valid from 2022-0101. European Committee on Antimicrobial Susceptibility Testing, Vaxjo, Sweden. Available from: https://www.eucast. org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_ tables/v_12.0_Breakpoint_Tables.pdf google scholar
11. 11. Çakar A, Akyön Y, Gür D, Karatuna O, Öğünç D, Özhak Baysan B, et al. Investigation of Carbapenemases in Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae Strains Isolated in 2014 in Turkey. Mikrobiyol Bul 2016;50(1):21-33. [CrossRef] google scholar
12. 12. Doyle D, Peirano G, Lascols C, Lloyd T, Church DL, Pitout JDD. Laboratory detection of Enterobacteriaceae that produce carbapenemases. J Clin Microbiol 2012;50(12):3877-80. [CrossRef] google scholar
13. 13. Ellington MJ, Kistler J, Livermore DM, Woodford N. Multiplex PCR for rapid detection of genes encoding acquired metallo- B-lactamases. J Antimicrob Chemother 2007;59(2):321-2. [CrossRef] google scholar
14. 14. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing B-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001;45(4):1151-61. [CrossRef] google scholar
15. 15. Sid Ahmed MA, Abdel Hadi H, Hassan AAI, Abu Jarir S, Al-Maslamani MA, Eltai NO, et al. Evaluation of in vitro activity of ceftazidime/avibactam and ceftolozane/tazobactam against MDR Pseudomonas aeruginosa isolates from Qatar. J Antimicrob Chemother 2019;74(12):3497-504. [CrossRef] google scholar
16. 16. Malekzadegan Y, Abdi A, Heidari H, Moradi M, Rastegar E, Ebrahim-Saraie HS. In vitro activities of colistin, imipenem and ceftazidime against drug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii isolates in the south of Iran. BMC Res Notes 2019;12(1):301. [CrossRef] google scholar
17. 17. Lee Y, Lu M, Shao P, Lu P, Chen Y, Cheng S, et al. Nationwide surveillance of antimicrobial resistance among clinically important Gram-negative bacteria, with an emphasis on carbapenems and colistin: Results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2018. Int J Antimicrob Agents 2019;54(3):318-28. [CrossRef] google scholar
18. 18. Savov E, Trifonova A, Kovachka K, Kjosseva E, Strateva T. Antimicrobial in vitro activities of ceftazidime-avibactam, meropenem-vaborbactam and plazomicin against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa-a pilot Bulgarian study. Infect Dis (Lond) 2019;51(11-12):870-3. [CrossRef] google scholar
19. 19. Livermore DM, Meunier D, Hopkins KL, Doumith M, Hill R, Pike R, et al. Activity of ceftazidime/avibactam against problem Enterobacteriaceae and Pseudomonas aeruginosa in the UK, 2015-16. J Antimicrob Chemother 2018;73(3):648-57. [CrossRef] google scholar
20. 20. Kazmierczak KM, de Jonge BLM, Stone GG, Sahm DF. In vitro activity of ceftazidime/avibactam against isolates of Pseudomonas aeruginosa collected in European countries: INFORM global surveillance 2012-15. J Antimicrob Chemother 2018;73(10):2777-81. [CrossRef] google scholar
21. 21. El-Sayed Ahmed MAEG, Zhong LL, Shen C, Yang Y, Doi Y, Tian GB. Colistin and its role in the era of antibiotic resistance: an extended review (2000-2019). Emerg Microbes Infect 2020;9(1):868-85. [CrossRef] google scholar
22. 22. Acar A, Karaahmetoğlu G, Akalın H, Altay AF. Pooled prevalence and trends of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates over the past 10 years in Turkey: A meta-analysis. J Glob Antimicrob Resist 2019;18:64-70. [CrossRef] google scholar
23. 23. Çiçek AÇ, Ertürk A, Ejder N, Rakici E, Kostakoğlu U, Yıldız İE, et al. Screening of antimicrobial resistance genes and epidemiological features in hospital and community-associated carbapenem-resistant Pseudomonas aeruginosa infections. Infect Drug Resist. 2021;14:1517-26. [CrossRef] google scholar
24. 24. Kiratisin P, Kazmierczak K, Stone GG. In vitro activity of ceftazidime/avibactam and comparators against carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa isolates collected globally between 2016 and 2018. J Glob Antimicrob Resist. 2021;27:132-41. [CrossRef] google scholar
25. 25. Karlowsky JA, Bouchillon SK, Benaouda A, Soraa N, Zerouali K, Mohamed N, et al. Antimicrobial susceptibility testing of clinical isolates of Gram-negative bacilli collected in Morocco by the ATLAS global surveillance program from 2018 to 2020. J Glob Antimicrob Resist 2022;S2213-7165(22)00090-X. [CrossRef] google scholar
26. 26. Chew KL, La M-V, Lin RTP, Teo JWP. Colistin and polymyxin B susceptibility testing for carbapenem-resistant and mcr-positive Enterobacteriaceae: Comparison of Sensititre, MicroScan, Vitek 2, and Etest with Broth Microdilution. J Clin Microbiol 2017; 55(9):2609-2616. [CrossRef] google scholar