Genişlemiş Spektrumlu Beta-Laktamaz Üreten Enterobacteriaceae İzolatlarına Karşı Seftazidim- Avibaktam’ın in Vitro Etkinliğinin Araştırılması
Yıl 2023,
Cilt: 8 Sayı: 1, 17 - 23, 29.03.2023
Melek Bilgin
,
Hacer İşler
,
Eşe Başbulut
,
Selim Görgün
Öz
Amaç: Tüm dünyada son yıllarda Enterobacteriaceae ailesi üyeleri arasında çoklu ilaç direncine sahip izolatlar artış göstermekte ve enfeksiyonların tedavisinde zorluklara yol açmaktadır. Bu çalışmanın amacı, Genişlemiş Spektrumlu Beta-Laktamaz Üreten ve karbapenem dirençli Enterobacteriaceae izolatlarına karşı seftazidim-avibaktam’ın in vitro etkinliğinin araştırılmasıdır.
Yöntem: Çalışmaya, laboratuvarımıza gönderilen çeşitli örneklerden izole edilen, genişlemiş spektrumlu beta-laktamaz üreten 114 Enterobacteriaceae türü dahil edildi. İzolatların tanımlanması ve antimikrobiyal duyarlılıkları otomatize sistemler kullanılarak gerçekleştirildi. İzolatların seftazidim avibaktama duyarlılıklarının saptanması amacıyla CAZ/AV 10/4 mg (Bioanalyse) ile disk difüzyon testi; zon çaplarının değerlendirilmesi için European Committee on Antimicrobial Susceptibility Testing (EUCAST) rehberi kullanılmıştır.
Bulgular: Çalışmaya 42 tanesi (%36.8) Escherichiae coli ve 72 tanesi (%63,2) Klebsiella pnemoniae olmak üzere toplam 114 tane Enterobacterales suşu dahil edildi. Suşların %44.7’si idrar örneklerinden izole edilmiştir. Tüm izolatların 67 (%58.8)’si karbapenemlere duyarlı iken, 47 (%41.2)’si karbapenemlere dirençli olarak bulundu. 103 tanesi (%90,4) ceftazidim avibactama duyarlı iken, 11 tanesi (%9,6) dirençli olarak saptandı.
Sonuç: Genişlemiş spektrumlu beta-laktamaz üreten veya metallo-β-laktamaz dışında karbapenem dirençli Enterobacteriaceae suşları için mevcut en iyi tedavi seçeneği, mümkün olduğunda ve fiyatın kullanımına izin verdiği durumlarda seftazidime-avibaktamdır.
Kaynakça
- Özinel MA. Enterobacteriaceae. Wilke Topçu A, Söyletir G, Doğanay M (Eds.). ‘Enfeksiyon Hastalıkları ve Mikrobiyolojisi: Etkenlere Göre Enfeksiyonlar’ kitabı. İstanbul: Nobel Tıp Kitabevleri 2008;2126- 36.
- 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. Doi: 10.3389/ fmicb.2019.00080.
- Kaye KS, Pogue JM. Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management. Pharmacotherapy 2015;35(10): 949–962. Doi: 10.1002/ phar.1636.
- Shirley M. Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram Negative Bacterial Infections. Drugs 2018 Apr;78(6):675-692. Doi: 10.1007/s40265- 018-0902-x. PMID: 29671219.
- Mashni O, Nazer L, Le J. Critical Review of Double-Carbapenem Therapy for the Treatment of Carbapenemase-Producing Klebsiella pneumoniae. The Annals of pharmacotherapy 2019;53(1): 70–81. Doi: 10.1177/1060028018790573.
- Doi, Yohei. Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2019. 69. S565-S575. 10.1093/cid/ciz830.
- Ayhan M. Çoklu İlaca Dirençli Gram negatif Mikroorganizmalarla Gelişen Enfeksiyonlarda Yeni Tedavi Seçenekleri. Ankara Üniversitesi Tıp Fakültesi Mecmuası 2020;73(2):96-101. Doi: 10.4274/atfm. galenos.2020.92408
- Clinical and Laboratory Standards Institute. Performance standarts for antimicrobial susceptibility testing. 24th informational supplement. CLSI Document M100-S24, CLSI, Wayne, PA, 2014.
- European Committee on Antimicrobial Susceptibility Testing Breakpoint tables for interpretation of MICs and zone diameters Version 12.0, 2022.
- Martin RM, Bachman MA. Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Frontiers in cellular and infection microbiology 2018;8: 4. Doi: 10.3389/fcimb.2018.00004.
- Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nature reviews Microbiology 2015;13(5): 269–284. doi: 10.1038/nrmicro3432.
- Zhang W, Guo Y, Li J, et al. In vitro and in vivo bactericidal activity of ceftazidime avibactam against Carbapenemase producing Klebsiella pneumoniae. Antimicrob Resist Infect Control 2018 Nov 21;7:142. Doi:10.1186/s13756-018-0435-9. 13. WHO. World Health Organization. [https:// www. who.int/en/news-room/detail/27- 02-2017-whopublishes-list-of-bacteria-for which-new-antibioticsare-urgently-needed] (Erişim tarihi: 03 Ekim 2022)
- Pfeifer Y, Cullik A, Witte W. Resistance to cephalosporins and carbapenems in Gram-negative bacterial pathogens. Int J Med Microbiol 2010;300(6):371-9. Doi: 10.1016/j.ijmm.2010.04.005.
Altınkanat Gelmez G, Söyletir G. Genişlemiş spektrumlu beta laktamaz üreten Enterobacteriaceae’larda mutant engelleme konsantrasyonunun saptanması. Experimed 2018;8(1):1-6. Doi: 10.26650/ experimed.2018.377256
- Güzel M, Öcal D, Toker Önder İ, Akdoğan D, Bahar Erdem G, Akpınar O. Comparison of in Vitro Antimicrobial Efficacy of Ceftolozane Tazobactam and Ceftazidime-Avibactam Combination Against Carbapenem-Resistant Enterobacteriaceae Species Isolated from Various Clinical Specimens. Konuralp Medical Journal 2022;14(1): 75-80.
- 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.
- 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.
- Karlowsky JA, Kazmierczak KM, Bouchillon SK, de Jonge BLM, Stone GG, Sahm DF. In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015. Antimicrob Agents Chemother 2018;62(7): pii: e02569- e02517.
- Yin D, Wu S, Yang Y, et al. China Antimicrobial Surveillance Network (CHINET) Study Group. Results from the China Antimicrobial Surveillance Network (CHINET) in 2017 of the In VitroActivities of Ceftazidime-Avibactam and Ceftolozane Tazobactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother 2019;63(4): e02431-e02418.
- Caine E , Koyuncu Ozyurt O, Ongut G, Kasaroglu K , Yıldız E, Ogunc D, et al.. In Vitro Activities of Ceftazidime-Avibactam and Comparator Antimicrobial Agents Tested against ESBL Producing Urinary E. coli Isolates. Journal of Microbiology and Infectious Disease 2019;09(03): 112-115. Doi: 10.5799/jmid.614195.
- 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 multidrugresistant isolates of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. International Journal of Infectious Diseases 2017;62: 39-43.
- Isler B, Aslan AT, Akova M, Harris P, Paterson DL. Treatment strategies for OXA-48-like and NDM producing Klebsiella pneumoniae infections. Expert Rev Anti Infect Ther 2022;20(11): 1389-1400. Doi: 10.1080/14787210.2022.2128764
Investigation of In Vitro Activity of Ceftazidime-Avibactam against Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Isolates
Yıl 2023,
Cilt: 8 Sayı: 1, 17 - 23, 29.03.2023
Melek Bilgin
,
Hacer İşler
,
Eşe Başbulut
,
Selim Görgün
Öz
Objectives: In recent years, isolates with multi-drug resistance have increased among Enterobacteriaceae family members all over the world, and has led to difficulties in the treatment of infections. The aim of this study was to investigate the in vitro efficacy of ceftazidime-avibactam against extended spectrum beta-lactamase producing and carbapenem-resistant Enterobacteriaceae isolates.
Methods: A total of 114 extended-spectrum beta-lactamase-producing Enterobacteriaceae species isolated from various samples sent to our laboratory were included in the study. Identification and antimicrobial susceptibility of isolates were performed using automated systems. Disc diffusion test with CAZ/AV 10/4 mg (Bioanalyse) to determine the susceptibility of isolates to ceftazidime avibactam; European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline was used for the evaluation of zone diameters.
Results: A total of 114 Enterobacterales strains, 42 (36.8%) Escherichiae coli and 72 (63.2%) Klebsiella pneumoniae, were included in the study. 44.7% of the strains were isolated from urine samples. While 67 (58.8%) of all isolates were susceptible to carbapenems, 47 (41.2%) were found to be resistant to carbapenems. While 103 (90.4%) were susceptible to ceftazidime avibactam, 11 (9.6%) were found to be resistant.
Conclusion: Ceftazidime-avibactam is the best available treatment for extended-spectrum beta-lactamase-producing or carbapenem-resistant strains of Enterobacteriaceae other than Metallo-β-lactamase, when available and price permits.
Kaynakça
- Özinel MA. Enterobacteriaceae. Wilke Topçu A, Söyletir G, Doğanay M (Eds.). ‘Enfeksiyon Hastalıkları ve Mikrobiyolojisi: Etkenlere Göre Enfeksiyonlar’ kitabı. İstanbul: Nobel Tıp Kitabevleri 2008;2126- 36.
- 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. Doi: 10.3389/ fmicb.2019.00080.
- Kaye KS, Pogue JM. Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management. Pharmacotherapy 2015;35(10): 949–962. Doi: 10.1002/ phar.1636.
- Shirley M. Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram Negative Bacterial Infections. Drugs 2018 Apr;78(6):675-692. Doi: 10.1007/s40265- 018-0902-x. PMID: 29671219.
- Mashni O, Nazer L, Le J. Critical Review of Double-Carbapenem Therapy for the Treatment of Carbapenemase-Producing Klebsiella pneumoniae. The Annals of pharmacotherapy 2019;53(1): 70–81. Doi: 10.1177/1060028018790573.
- Doi, Yohei. Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2019. 69. S565-S575. 10.1093/cid/ciz830.
- Ayhan M. Çoklu İlaca Dirençli Gram negatif Mikroorganizmalarla Gelişen Enfeksiyonlarda Yeni Tedavi Seçenekleri. Ankara Üniversitesi Tıp Fakültesi Mecmuası 2020;73(2):96-101. Doi: 10.4274/atfm. galenos.2020.92408
- Clinical and Laboratory Standards Institute. Performance standarts for antimicrobial susceptibility testing. 24th informational supplement. CLSI Document M100-S24, CLSI, Wayne, PA, 2014.
- European Committee on Antimicrobial Susceptibility Testing Breakpoint tables for interpretation of MICs and zone diameters Version 12.0, 2022.
- Martin RM, Bachman MA. Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Frontiers in cellular and infection microbiology 2018;8: 4. Doi: 10.3389/fcimb.2018.00004.
- Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nature reviews Microbiology 2015;13(5): 269–284. doi: 10.1038/nrmicro3432.
- Zhang W, Guo Y, Li J, et al. In vitro and in vivo bactericidal activity of ceftazidime avibactam against Carbapenemase producing Klebsiella pneumoniae. Antimicrob Resist Infect Control 2018 Nov 21;7:142. Doi:10.1186/s13756-018-0435-9. 13. WHO. World Health Organization. [https:// www. who.int/en/news-room/detail/27- 02-2017-whopublishes-list-of-bacteria-for which-new-antibioticsare-urgently-needed] (Erişim tarihi: 03 Ekim 2022)
- Pfeifer Y, Cullik A, Witte W. Resistance to cephalosporins and carbapenems in Gram-negative bacterial pathogens. Int J Med Microbiol 2010;300(6):371-9. Doi: 10.1016/j.ijmm.2010.04.005.
Altınkanat Gelmez G, Söyletir G. Genişlemiş spektrumlu beta laktamaz üreten Enterobacteriaceae’larda mutant engelleme konsantrasyonunun saptanması. Experimed 2018;8(1):1-6. Doi: 10.26650/ experimed.2018.377256
- Güzel M, Öcal D, Toker Önder İ, Akdoğan D, Bahar Erdem G, Akpınar O. Comparison of in Vitro Antimicrobial Efficacy of Ceftolozane Tazobactam and Ceftazidime-Avibactam Combination Against Carbapenem-Resistant Enterobacteriaceae Species Isolated from Various Clinical Specimens. Konuralp Medical Journal 2022;14(1): 75-80.
- 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.
- 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.
- Karlowsky JA, Kazmierczak KM, Bouchillon SK, de Jonge BLM, Stone GG, Sahm DF. In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015. Antimicrob Agents Chemother 2018;62(7): pii: e02569- e02517.
- Yin D, Wu S, Yang Y, et al. China Antimicrobial Surveillance Network (CHINET) Study Group. Results from the China Antimicrobial Surveillance Network (CHINET) in 2017 of the In VitroActivities of Ceftazidime-Avibactam and Ceftolozane Tazobactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother 2019;63(4): e02431-e02418.
- Caine E , Koyuncu Ozyurt O, Ongut G, Kasaroglu K , Yıldız E, Ogunc D, et al.. In Vitro Activities of Ceftazidime-Avibactam and Comparator Antimicrobial Agents Tested against ESBL Producing Urinary E. coli Isolates. Journal of Microbiology and Infectious Disease 2019;09(03): 112-115. Doi: 10.5799/jmid.614195.
- 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 multidrugresistant isolates of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. International Journal of Infectious Diseases 2017;62: 39-43.
- Isler B, Aslan AT, Akova M, Harris P, Paterson DL. Treatment strategies for OXA-48-like and NDM producing Klebsiella pneumoniae infections. Expert Rev Anti Infect Ther 2022;20(11): 1389-1400. Doi: 10.1080/14787210.2022.2128764