Research Article
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Year 2025, Volume: 32 Issue: 4, 319 - 326, 01.12.2025
https://doi.org/10.17343/sdutfd.1748282

Abstract

References

  • 1. Zhen S, Wang H, Feng S. Update of clinical application in ceftazidime–avibactam for multidrug-resistant Gram-negative bacteria infections. Infection. 2022;50(6):1409-1423.
  • 2. Aslan AT, Ezure Y, Horcajada JP, et al. In vitro, in vivo, and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa isolates or infections: a scoping review. Frontiers in Medicine. 2023;10:1249030.
  • 3. Yahav D, Giske CG, Grāmatniece A, et al. New β-lactam-β-lactamase inhibitor combinations. Clin Microbiol Rev 2021;34:e00115-20.
  • 4. Boucher HW, Talbot GH, Benjamin DK, et al. 10×20 progress-development of new drugs active against Gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis. 2013;56:1685-1694.
  • 5. Wang Y, Wang J, Wang R, et al. Resistance to ceftazidime-avibactam and underlying mechanisms. J Glob Antimicrob Resist 2020;22:18-27.
  • 6. Nichols WW, de Jonge BLM, Kazmierczak KM, et al. In vitro susceptibility of global surveillance isolates of Pseudomonas aeruginosa to ceftazidime-avibactam (INFORM 2012 to 2014). Antimicrob Agents Chemother 2016;60:4743-4749.
  • 7. Shields RK, Clancy CJ, Pasculle AW, et al. Verification of ceftazidime-avibactam and ceftolozane-tazobactam susceptibility testing methods against carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa. Journal of clinical microbiology 2018;56(2):10-1128.
  • 8. Park BY, Mourad D, Hong JS, et al. Performance evaluation of the newly developed BD Phoenix NMIC-500 panel using clinical isolates of gram-negative bacilli. Annals of laboratory medicine, 2019;39(5):470.
  • 9. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters, Version 11.0, valid from 2021-01-01, 2021.
  • 10. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters, Version 12.0, valid from 2022-01-01, 2022.
  • 11. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters, Version 13.0, valid from 2023-01-01, 2023.
  • 12. Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis 2008;197:1079-81.
  • 13. Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1-12.
  • 14. Kazmierczak KM, de Jonge B L, Stone GG, et al. In vitro activity of ceftazidime/avibactam against isolates of Enterobacteriaceae collected in European countries: INFORM global surveillance 2012–15. Journal of Antimicrobial Chemotherapy 2018;73(10):2782-2788.
  • 15. Sader HS, Huband MD, Castanheira M, et al. Pseudomonas aeruginosa antimicrobial susceptibility results from four years (2012 to 2015) of the International Network for Optimal Resistance Monitoring program in the United States. Antimicrob Agents Chemother 2017;61:e02252-16.
  • 16. ATLAS surveillance program. Access address: www.atlas-surveillance.com (accessed on May 2025)
  • 17. Humphries R, Campeau S, Davis TE, Nagaro KJ, LaBombardi VJ, Franklin S, Heimbach L, Dwivedi HP. Multicenter Evaluation of Ceftazidime-Avibactam Susceptibility Testing of Enterobacterales and Pseudomonas aeruginosa on the Vitek 2 System. J Clin Microbiol. 2021;18;59(3): e01870-20.
  • 18. Cetinkol Y, Yildirim AA, Calgin MK. Evaluation of ceftazidime-avibactam efficacy in gram negative bacteria. Medicine Science. 2022;11(3).
  • 19. Koca O, Aydin Tigli G, Ozen HN, et al. Evaluation of ceftazidime-avibactam susceptibility in carbapenem resistant Klebsiella pneumoniae and Pseudomonas aeruginosa isolates. J Med Palliat Care. 2023;4(6):625-9.
  • 20. Bilgin M, İşler H, Başbulut E, et al. Genişlemiş Spektrumlu Beta-Laktamaz Üreten Enterobacteriaceae İzolatlarına Karşı Seftazidim- Avibaktam’ın in Vitro Etkinliğinin Araştırılması. Journal of Immunology and Clinical Microbiology. 2023;8(1):17-23.
  • 21. Öztaş S, Er DK, Dündar D. Karbapenemlere dirençli ve duyarlı Klebsiella pneumoniae izolatlarının çeşitli antimikrobiyallere direnç oranları. KOU Sag Bil Derg. 2022;8(3):229-32.
  • 22. Arıcı N, Kansak N, Adaleti R, et al. Ventilatör ilişkili pnömoni etkeni karbapenem dirençli Klebsiella pneumoniae ve Pseudomonas aeruginosa izolatlarında seftazidim-avibaktamın in vitro etkinliği. ANKEM Derg. 2023;37(2):57-64.
  • 23. Akbaş E, Keskin BH, Kayman H, et al. Çok ilaca dirençli gram negatif bakterilerdeki seftazidim-avibaktam duyarlılığının araştırılması. ANKEM Dergisi. 2023;37(3):103-108.
  • 24. Yakut S, Ulaba A, Alataş Eroğlu A, et al. Escherichia coli, Klebsiella pneumoniae ve Pseudomonas aeruginosa suşlarında seftazidim-avibaktam in vitro duyarlılığının araştırılması. Turk Mikrobiyol Cemiy Derg. 2024;54(4):288-294.
  • 25. Uğurlu H, Küçük B, Orak F, et al. Karbapenem dirençli Enterobactericeae türlerinin antibiyotik duyarlılıklarının iki farklı panelle (Phoenix BD) karşılaştırılması. KSÜ Tıp Fak Der. 2023;8(1):22-7.
  • 26. Mermutluoğlu Ç, Çiftçi EZ, Özcan N, et al. Klinik örneklerden izole edilen karbapenem dirençli Klebsiella pneumoniae ve Escherichia coli suşlarında antibiyotik duyarlılıklarının araştırılması: Kapsamlı bir sağlık kuruluşunda dört yıllık analiz. Van Tıp Derg. 2023;30(4):374-81.
  • 27. Albichr IS, Anantharajah A, Dodémont M, et al. Evaluation of the automated BD Phoenix CPO Detect test for detection and classification of carbapenemases in Gram negatives. Diagnostic microbiology and infectious disease. 2020;96(2):114911.
  • 28. Hoşbul T, Aydogan CN, Kaya S, et al. Karbapenem dirençli Klebsiella pneumoniae klinik izolatlarına karşı seftazidim-avibaktam ve kolistinin in vitro etkinliği. Mikrobiyol Bul. 2022;56(2):218-229.
  • 29. Hosbul T, Aydogan CN, Kaya S, et al. In vitro activity of ceftazidime-avibactam and colistin against carbapenem-resistant Pseudomonas aeruginosa clinical isolates. J Ist Faculty Med 2022;85(3):355-61.
  • 30. Köle M, Sesli Çetin E, Şirin MC, et al. Seftazidim-avibaktam, meropenem ve kolistinin tek başına ve ikili kombinasyonlarının çeşitli klinik örneklerden izole edilen karbapenem dirençli Klebsiella pneumoniae suşlarına karşı in vitro etkinliğinin araştırılması. Mikrobiyol Bul. 2022;56(2):230-250.
  • 31. Schaumburg F, Bletz S, Mellmann A, et al. Comparison of methods to analyse susceptibility of German MDR/XDR Pseudomonas aeruginosa to ceftazidime/avibactam. Int J Antimicrob Agents. 2019;54(2):255-260.
  • 32. Wenzler E, Lee M, Wu TJ, et al. Performance of ceftazidime/avibactam susceptibility testing methods against clinically relevant Gram-negative organisms. Journal of Antimicrobial Chemotherapy. 2019;74(3):633-638.
  • 33. Wang Q, Zhang F, Wang Z, et al. Evaluation of the Etest and disk diffusion method for detection of the activity of ceftazidime-avibactam against Enterobacterales and Pseudomonas aeruginosa in China. BMC Microbiology.2020;20:1-7.
  • 34. Daragon B, Fournier D, Plésiat P, et al. Performance of disc diffusion, MIC gradient tests and Vitek 2 for ceftolozane/tazobactam and ceftazidime/avibactam susceptibility testing of Pseudomonas aeruginosa. Journal of Antimicrobial Chemotherapy. 2021;76(10):2586-2592.
  • 35. Zhang J, Li G, Zhang G, et al. Performance Evaluation of the Gradient Diffusion Strip Method and Disk Diffusion Method for Ceftazidime-Avibactam Against Enterobacterales and Pseudomonas aeruginosa: A Dual-Center Study. Front Microbiol. 2021;16:12:710526.
  • 36. Sharma B, Sreenivasan P, Angrup A, et al. In-vitro Susceptibility Testing Methods for Ceftazidime-avibactam against Carbapenem-resistant Enterobacterales: Comparison with Reference Broth Microdilution Method. Curr Drug Saf. 2023;18(4):563-570.

Evaluation of Ceftazidime-Avibactam Susceptibility in Carbapenem-Resistant Gram-Negative Bacteria

Year 2025, Volume: 32 Issue: 4, 319 - 326, 01.12.2025
https://doi.org/10.17343/sdutfd.1748282

Abstract

Objective: Resistance to carbapenem antibiotics, commonly preferred to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, is gradually increasing. Ceftazidime-avibactam (CZA) is a novel beta-lactam/beta-lactamase inhibitor combination, proposed as an alternative treatment option for severe infections caused by carbapenem-resistant Gram-negative bacteria. This study aimed to determine the susceptibility of carbapenem-resistant Klebsiella pneumoniae (CR-KP), carbapenem-resistant Escherichia coli (CR-EC), and carbapenem-resistant Pseudomonas aeruginosa (CR-PA) isolates to CZA using the Kirby-Bauer disk diffusion method (DDM) and the BD Phoenix automated system, and to compare the results.
Material and Method: A total of 320 strains (209 CR-KP, 53 CR-EC, and 58 CR-PA) resistant to at least one carbapenem (ertapenem, imipenem, and meropenem), collected between August 2021 and August 2023, were included in the study. CZA susceptibility testing was performed using the DDM and the CPO detect panel of the BD Phoenix automated system (Becton Dickinson, USA). Results were interpreted in accordance with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards.
Results: While CZA susceptibility rates determined by the automated system were 74.1% for CR-KP, 64.5% for CR-EC, and 90.9% for CR-PA, the DDM method yielded susceptibility rates of 87.8% for CR-KP, 94.4% for CR-EC, and 81.3% for CR-PA. Categorical agreement was observed in 86.9% of 115 isolates tested by both methods. Although not statistically significant, a declining trend in CZA susceptibility was observed over the years with both methods.
Conclusion: CZA susceptibility rates among carbapenem-resistant Gram-negative isolates in our hospital were consistent with current global data. Determining accurate CZA susceptibility results is important for guiding effective treatment strategies against infections caused by carbapenem-resistant bacteria. The observed discrepancies in susceptibility results between the DDM and the automated system, particularly across different species, underscore the need for further species-specific studies to identify the most reliable testing methodology for CZA susceptibility.

Ethical Statement

This study was approved by the Ethics Committee of the Faculty of Medicine, Suleyman Demirel University (decision no: 38, date 12.05.2025). The study was conducted in accordance with the principles set forth in the Declaration of Helsinki.

References

  • 1. Zhen S, Wang H, Feng S. Update of clinical application in ceftazidime–avibactam for multidrug-resistant Gram-negative bacteria infections. Infection. 2022;50(6):1409-1423.
  • 2. Aslan AT, Ezure Y, Horcajada JP, et al. In vitro, in vivo, and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa isolates or infections: a scoping review. Frontiers in Medicine. 2023;10:1249030.
  • 3. Yahav D, Giske CG, Grāmatniece A, et al. New β-lactam-β-lactamase inhibitor combinations. Clin Microbiol Rev 2021;34:e00115-20.
  • 4. Boucher HW, Talbot GH, Benjamin DK, et al. 10×20 progress-development of new drugs active against Gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis. 2013;56:1685-1694.
  • 5. Wang Y, Wang J, Wang R, et al. Resistance to ceftazidime-avibactam and underlying mechanisms. J Glob Antimicrob Resist 2020;22:18-27.
  • 6. Nichols WW, de Jonge BLM, Kazmierczak KM, et al. In vitro susceptibility of global surveillance isolates of Pseudomonas aeruginosa to ceftazidime-avibactam (INFORM 2012 to 2014). Antimicrob Agents Chemother 2016;60:4743-4749.
  • 7. Shields RK, Clancy CJ, Pasculle AW, et al. Verification of ceftazidime-avibactam and ceftolozane-tazobactam susceptibility testing methods against carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa. Journal of clinical microbiology 2018;56(2):10-1128.
  • 8. Park BY, Mourad D, Hong JS, et al. Performance evaluation of the newly developed BD Phoenix NMIC-500 panel using clinical isolates of gram-negative bacilli. Annals of laboratory medicine, 2019;39(5):470.
  • 9. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters, Version 11.0, valid from 2021-01-01, 2021.
  • 10. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters, Version 12.0, valid from 2022-01-01, 2022.
  • 11. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters, Version 13.0, valid from 2023-01-01, 2023.
  • 12. Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis 2008;197:1079-81.
  • 13. Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1-12.
  • 14. Kazmierczak KM, de Jonge B L, Stone GG, et al. In vitro activity of ceftazidime/avibactam against isolates of Enterobacteriaceae collected in European countries: INFORM global surveillance 2012–15. Journal of Antimicrobial Chemotherapy 2018;73(10):2782-2788.
  • 15. Sader HS, Huband MD, Castanheira M, et al. Pseudomonas aeruginosa antimicrobial susceptibility results from four years (2012 to 2015) of the International Network for Optimal Resistance Monitoring program in the United States. Antimicrob Agents Chemother 2017;61:e02252-16.
  • 16. ATLAS surveillance program. Access address: www.atlas-surveillance.com (accessed on May 2025)
  • 17. Humphries R, Campeau S, Davis TE, Nagaro KJ, LaBombardi VJ, Franklin S, Heimbach L, Dwivedi HP. Multicenter Evaluation of Ceftazidime-Avibactam Susceptibility Testing of Enterobacterales and Pseudomonas aeruginosa on the Vitek 2 System. J Clin Microbiol. 2021;18;59(3): e01870-20.
  • 18. Cetinkol Y, Yildirim AA, Calgin MK. Evaluation of ceftazidime-avibactam efficacy in gram negative bacteria. Medicine Science. 2022;11(3).
  • 19. Koca O, Aydin Tigli G, Ozen HN, et al. Evaluation of ceftazidime-avibactam susceptibility in carbapenem resistant Klebsiella pneumoniae and Pseudomonas aeruginosa isolates. J Med Palliat Care. 2023;4(6):625-9.
  • 20. Bilgin M, İşler H, Başbulut E, et al. Genişlemiş Spektrumlu Beta-Laktamaz Üreten Enterobacteriaceae İzolatlarına Karşı Seftazidim- Avibaktam’ın in Vitro Etkinliğinin Araştırılması. Journal of Immunology and Clinical Microbiology. 2023;8(1):17-23.
  • 21. Öztaş S, Er DK, Dündar D. Karbapenemlere dirençli ve duyarlı Klebsiella pneumoniae izolatlarının çeşitli antimikrobiyallere direnç oranları. KOU Sag Bil Derg. 2022;8(3):229-32.
  • 22. Arıcı N, Kansak N, Adaleti R, et al. Ventilatör ilişkili pnömoni etkeni karbapenem dirençli Klebsiella pneumoniae ve Pseudomonas aeruginosa izolatlarında seftazidim-avibaktamın in vitro etkinliği. ANKEM Derg. 2023;37(2):57-64.
  • 23. Akbaş E, Keskin BH, Kayman H, et al. Çok ilaca dirençli gram negatif bakterilerdeki seftazidim-avibaktam duyarlılığının araştırılması. ANKEM Dergisi. 2023;37(3):103-108.
  • 24. Yakut S, Ulaba A, Alataş Eroğlu A, et al. Escherichia coli, Klebsiella pneumoniae ve Pseudomonas aeruginosa suşlarında seftazidim-avibaktam in vitro duyarlılığının araştırılması. Turk Mikrobiyol Cemiy Derg. 2024;54(4):288-294.
  • 25. Uğurlu H, Küçük B, Orak F, et al. Karbapenem dirençli Enterobactericeae türlerinin antibiyotik duyarlılıklarının iki farklı panelle (Phoenix BD) karşılaştırılması. KSÜ Tıp Fak Der. 2023;8(1):22-7.
  • 26. Mermutluoğlu Ç, Çiftçi EZ, Özcan N, et al. Klinik örneklerden izole edilen karbapenem dirençli Klebsiella pneumoniae ve Escherichia coli suşlarında antibiyotik duyarlılıklarının araştırılması: Kapsamlı bir sağlık kuruluşunda dört yıllık analiz. Van Tıp Derg. 2023;30(4):374-81.
  • 27. Albichr IS, Anantharajah A, Dodémont M, et al. Evaluation of the automated BD Phoenix CPO Detect test for detection and classification of carbapenemases in Gram negatives. Diagnostic microbiology and infectious disease. 2020;96(2):114911.
  • 28. Hoşbul T, Aydogan CN, Kaya S, et al. Karbapenem dirençli Klebsiella pneumoniae klinik izolatlarına karşı seftazidim-avibaktam ve kolistinin in vitro etkinliği. Mikrobiyol Bul. 2022;56(2):218-229.
  • 29. Hosbul T, Aydogan CN, Kaya S, et al. In vitro activity of ceftazidime-avibactam and colistin against carbapenem-resistant Pseudomonas aeruginosa clinical isolates. J Ist Faculty Med 2022;85(3):355-61.
  • 30. Köle M, Sesli Çetin E, Şirin MC, et al. Seftazidim-avibaktam, meropenem ve kolistinin tek başına ve ikili kombinasyonlarının çeşitli klinik örneklerden izole edilen karbapenem dirençli Klebsiella pneumoniae suşlarına karşı in vitro etkinliğinin araştırılması. Mikrobiyol Bul. 2022;56(2):230-250.
  • 31. Schaumburg F, Bletz S, Mellmann A, et al. Comparison of methods to analyse susceptibility of German MDR/XDR Pseudomonas aeruginosa to ceftazidime/avibactam. Int J Antimicrob Agents. 2019;54(2):255-260.
  • 32. Wenzler E, Lee M, Wu TJ, et al. Performance of ceftazidime/avibactam susceptibility testing methods against clinically relevant Gram-negative organisms. Journal of Antimicrobial Chemotherapy. 2019;74(3):633-638.
  • 33. Wang Q, Zhang F, Wang Z, et al. Evaluation of the Etest and disk diffusion method for detection of the activity of ceftazidime-avibactam against Enterobacterales and Pseudomonas aeruginosa in China. BMC Microbiology.2020;20:1-7.
  • 34. Daragon B, Fournier D, Plésiat P, et al. Performance of disc diffusion, MIC gradient tests and Vitek 2 for ceftolozane/tazobactam and ceftazidime/avibactam susceptibility testing of Pseudomonas aeruginosa. Journal of Antimicrobial Chemotherapy. 2021;76(10):2586-2592.
  • 35. Zhang J, Li G, Zhang G, et al. Performance Evaluation of the Gradient Diffusion Strip Method and Disk Diffusion Method for Ceftazidime-Avibactam Against Enterobacterales and Pseudomonas aeruginosa: A Dual-Center Study. Front Microbiol. 2021;16:12:710526.
  • 36. Sharma B, Sreenivasan P, Angrup A, et al. In-vitro Susceptibility Testing Methods for Ceftazidime-avibactam against Carbapenem-resistant Enterobacterales: Comparison with Reference Broth Microdilution Method. Curr Drug Saf. 2023;18(4):563-570.
There are 36 citations in total.

Details

Primary Language English
Subjects Medical Bacteriology
Journal Section Research Article
Authors

Tuğba Ayvalik Rüzgarkesen 0000-0003-0958-1502

Yaren Şekercioğlu 0009-0001-6114-9859

Muhammed Tevfik Erol 0009-0007-3209-8347

Göksel Bilir 0000-0002-0375-4188

Emel Sesli Çetin 0000-0001-5231-3824

Mümtaz Cem Şirin 0000-0002-7349-3438

Publication Date December 1, 2025
Submission Date July 22, 2025
Acceptance Date October 8, 2025
Published in Issue Year 2025 Volume: 32 Issue: 4

Cite

Vancouver Ayvalik Rüzgarkesen T, Şekercioğlu Y, Erol MT, Bilir G, Sesli Çetin E, Şirin MC. Evaluation of Ceftazidime-Avibactam Susceptibility in Carbapenem-Resistant Gram-Negative Bacteria. Med J SDU. 2025;32(4):319-26.

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