Comparison of in Vitro Antimicrobial Efficacy of Ceftolozane-Tazobactam and Ceftazidime-Avibactam Combination Against Carbapenem-Resistant Enterobacteriaceae Species Isolated from Various Clinical Specimens

Year 2022, , 75 - 80, 14.03.2022

Mustafa Güzel , Duygu Öcal , İlke Toker Önder , Doğan Akdoğan , Gül Bahar Erdem , Orhan Akpınar

https://doi.org/10.18521/ktd.1011899

Cited By: 2

Abstract

Objective: The increase in resistant Gram-negative bacteria is a major concern and has led to difficulties in the treatment of infections. The aim of this study was to compare the in vitro efficacy of CLZ-TAZ and CAZ-AVB combinations against carbapenem-resistant Enterobacteriaceae strains.

Methods: 80 carbapenem-resistant Enterobacteriaceae species isolated from various samples sent to our laboratory were included in the study. Identification and antimicrobial susceptibility of strains were performed using automated systems. The presence of carbapenemases in all isolates was tested using the CarbaNP test and the carbapenem inactivation method. The presence of carbapenemase genes was tested by multiplex PCR.

Results: The presence of carbapenemases was detected in 60 % E. coli isolates and in 78.5% K. pneumoniae isolates via phenotypic tests. OXA-48 enzyme was found in 73.7% of isolates containing carbapenemase. The second most common enzyme was NDM.The assessment of the efficacy of the β-lactam/β-lactamase inhibitor combinations against CRE isolates revealed that the activity of CAZ-AVB (77%) was higher than CLZ-TAZ (48%).

Conclusion: Our findings suggest that CAZ-AVB and CLZ-TAZ may be promising in the treatment of infections caused by CRE strains. Sensitivity rates were higher with ceftazidime-avibactam than with ceftolozane-tazobactam. The data obtained in this study will contribute to the clinical use of these agents in our country.

Keywords

Carbapenem-resistant Enterobacteriaceae, Ceftolozane/tazobactam, ceftazidime/avibactam, blaOXA-48, bla NDM

Çeşitli Klinik Örneklerden İzole Edilen Karbapenem Dirençli Enterobacteriaceae İzolatlarına Karşı Seftolozan-Tazobaktam ve Seftazidim-Avibaktam Kombinasyonlarının In Vitro Antimikrobiyal Etkinliğinin Karşılaştırılması

Abstract

Amaç: Dirençli gram negatif bakterilerdeki artış önemli bir endişe kaynağıdır ve enfeksiyonların tedavisinde zorluklara yol açmıştır. Bu çalışmanın amacı, carbapenem-resistant Enterobacteriaceae suşlarına karşı CLZ-TAZ ve CAZ-AVB kombinasyonlarının in vitro etkinliğini karşılaştırmaktır.
Gereç ve Yöntem: Çalışmaya, laboratuvarımıza gönderilen çeşitli örneklerden izole edilen, karbapenemlere dirençli 80 Enterobacteriaceae türü dahil edildi. İzolatların tanımlanması ve antimikrobiyal duyarlılıkları otomatize sistemler kullanılarak gerçekleştirildi. Tüm izolatlarda karbapenemazların varlığı, CarbaNP testi ve karbapenem inaktivasyon yöntemi kullanılarak test edildi. Karbapenemaz genlerinin varlığı multipleks PCR ile test edildi.
Bulgular: Fenotipik testler ile karbapenemazların varlığı %60 E. coli izolatında ve %78.5 K. pneumoniae izolatında tespit edildi. Karbapenemaz içeren izolatların %73.7'sinde OXA-48 enzimi bulundu. İkinci en yaygın enzim NDM idi. β-laktam/β-laktamaz inhibitör kombinasyonlarının CRE izolatlarına karşı etkinliğinin değerlendirilmesinde ise, CAZ-AVB'nin (%77) aktivitesinin CLZ-TAZ'dan (%48) daha yüksek olduğu tespit edildi.
Sonuç: Bulgularımız, CRE suşlarının neden olduğu enfeksiyonların tedavisinde CAZ-AVB ve CLZ-TAZ'ın umut verici olabileceğini düşündürmektedir. Seftazidim-avibaktam ile duyarlılık oranları, seftolozan-tazobaktamınkinden daha yüksekti. Bu çalışmada elde edilen veriler ülkemizde de bu ajanların klinik kullanımına katkı sağlayacaktır.

Keywords

Karbapenem dirençli Enterobacteriaceae, Seftolozan/Tazobaktam, Seftazidim/Avibaktam, blaOXA-48, bla NDM., bla NDM

References

• 1- Kaye KS, Pogue JM. Infections caused by resistant gram‐negative bacteria: epidemiology and management. Pharmacotherapy. 2015;35(10):949-962.
• 2-Sheu CC, Chang YT, Lin SY, Chen YH, Hsueh PR. Infections caused by carbapenem-resistant Enterobacteriaceae: an update on therapeutic options. Frontiers in microbiology. 2019;10:80.
• 3-Çaycı YT, Bıyık İ, Çınar C, Birinci A. Antimicrobial Resistance of Carbapenem-Resistant Enterobacteriaceae Isolates Between the Years of 2015-2018. Turk Mikrobiyol Cemiy Derg. 2020;50(3):134-140.
• 4 - 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.
• 5-Karaiskos I, Galani I, Souli M, Giamarellou H. Novel β-lactam-β-lactamase inhibitor combinations: expectations for the treatment of carbapenem-resistant Gram-negative pathogens. Expert opinion on drug metabolism & toxicology.2019;15(2):133-149.
• 6-World Health Organization. Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics;World Health Organization: Geneva, Switzerland, 2017; Available online: https://www.who.int/medicines/ publications/global-priority-list-antibiotic-resistant-bacteria/en/ (accessed on 30 December 2020).
• 7-Wilson G, Fitzpatrick M, Walding K, Gonzalez B, Schweizer ML, Suda KJ. Meta-analysis of Clinical Outcomes Using Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam for the Treatment of Multidrug Resistant Gram-Negative Infections. Open Forum Infectious Diseases. 2021;8(2):ofaa651
• 8-Şahin F, Kıyan M, Karasartova D, Çalgın MK, Akhter S. A new method for the disruption of cell walls of gram-positive bacteria and mycobacteria on the point of nucleic acid extraction: sand method. Mikrobiyol Bul.2016;50(1):34-43.
• 9. Gülmez D, Woodford N, Palepou MFI, Mushtaq S, Metan G, Yakupogullari Y. Carbapenem-resistant Escherichia coli and Klebsiella pneumoniae isolates from Turkey with OXA-48-like carbapenemases and outermembrane protein loss. Int J Antimicrob Agents. 2008;31(6):523-6.
• 10. Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenemresistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis. 2011;53(1):60-7.
• 11- Baran I, Aksu N. Phenotypic and genotypic characteristics of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Turkey. Annals of clinical microbiology and antimicrobials. 2016;15(1):1-11.
• 12-Celikbilek N, Unaldi O, Kirca F, Gozalan A, Acikgoz ZC, Durmaz R. Molecular characterization of carbapenem-resistant Klebsiella pneumoniae species isolated from a Tertiary Hospital, Ankara, Turkey. Jundishapur Journal of Microbiology. 2017;10(10): e14341
• 13-Uskudar GA, Guney M, Sig AK, Kilic S, Baysallar, MArising Prevalence of OXA-48 producer Escherichia coli and OXA-48 with NDM co-producer Klebsiella pneumoniae Strains. Revista Română de Medicină de Laborator .2019;27(3):319-326
• 14-Liao CH, Lee NY, Tang HJ, Lee SSJ, Lin CF, Lu PL, et al. Antimicrobial activities of ceftazidime–avibactam, ceftolozane–tazobactam, and other agents against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolated from intensive care units in Taiwan: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan in 2016. Infection and drug resistance.2019;12: 545-552.
• 15- Jean SS, Lee WS, Yu KW, Liao, CH, Hsu, CW, Chang FY,et al. Rates of susceptibility of carbapenems, ceftobiprole, and colistin against clinically important bacteria collected from intensive care units in 2007: results from the surveillance of multicenter antimicrobial resistance in Taiwan . J Microbiol Immunol Infect. 2016;49(6):969–976
• 16- Viala B, Zaidi FZ, Bastide M, Dumont Y, Le Moing V, Jean-Pierre H,et al. Assessment of the in vitro activities of ceftolozane/tazobactam and ceftazidime/avibactam in a collection of beta-lactam-resistant Enterobacteriaceae and Pseudomonas aeruginosa clinical isolates at Montpellier University Hospital, France. Microbial Drug Resistance. 2019;25(9):1325-1329.
• 17-Sader HS, Flamm RK, Carvalhaes CG, Castanheira M. Comparison of ceftazidime-avibactam and ceftolozane-tazobactam in vitro activities when tested against gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2017–2018). Diagnostic microbiology and infectious disease.2020;96(3):114833
• 18-Alatoom A, Elsayed H, Lawlor K, AbdelWareth L, El-Lababidi R, Cardona L,et al. Comparison of antimicrobial activity between ceftolozane–tazobactam and ceftazidime–avibactam against multidrug-resistant isolates of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. International Journal of Infectious Diseases. 2017;62:39-43.
• 19-Yin D, Wu S, Yang Y, Shi Q, Dong D, Zhu D,et al. Results from the China Antimicrobial Surveillance Network (CHINET) in 2017 of the in vitro activities of ceftazidime-avibactam and ceftolozane-tazobactam against clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrobial agents and chemotherapy. 2019;63(4):e02431-18.
• 20-Shortridge D, Pfaller MA, Castanheira M, Flamm RK. Antimicrobial Activity of Ceftolozane-Tazobactam Tested Against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2013-2016) as Part of the Surveillance Program: Program to Assess Ceftolozane-Tazobactam Susceptibility. Microb Drug Resist. 2018;24(5):563-577
• 21-Zhang P, Shi Q, Hu H, Hong B, Wu X, Du X, et al. Emergence of ceftazidime/avibactam resistance in carbapenem-resistant Klebsiella pneumoniae in China. Clinical Microbiology and Infection. 2020;26(1):124-e1.