In Vitro Efficacy of Ceftazidime-Avibactam in Carbapenem Resistant Klebsiella pneumoniae and Pseudomonas aeruginosa Isolates as Causative Agents of Ventilator-Associated Pneumonia
Abstract
Ventilator-associated pneumonia (VAP) is one of the most serious infections encountered in the intensive care unit (ICU). The aim of this study is to determine the in vitro efficacy of ceftazidime-avibactam against carbapenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa isolates isolated in our hospital as VAP agents. It also aimed to determine the frequency of colonization with the causative microorganism in endotracheal aspirate (ETA) screening samples, risk factors associated with VAP, and patient survival results.
In this retrospective study, patients who were hospitalized in Haydarpasa Numune Hospital ICU between September 2021 and December 2022 and received mechanical ventilation support for more than 48 hours and were diagnosed with VAP and ETA samples were included. MALDI-TOF (VITEK-MS, bioMérieux, France) method was used for the identification of the strains, and the VITEK 2 automated system (bioMérieux, France) was used for the determination of antibiotic susceptibility.
Ceftazidime-avibactam susceptibility was determined by disk diffusion method, resistant strains were also studied using gradient diffusion method (MIC strip, Liofilchem, Italy). The antibiotic susceptibility of the strains was evaluated according to the criteria of the European Committee on Antimicrobial Susceptibility Testing (EUCAST).
Microbiological data of the patients were obtained from the laboratory communication system, and clinical information was obtained from the electronic medical records in the hospital communication system.
Forty patients who developed VIP and with carbapenem resistant K. pneumoniae (n=18) and P. aeruginosa (n=22) isolated from their specimens included in the study. 22.2% of K. pneumoniae isolates and 86.4% of P. aeruginosa isolates were found resistant to ceftazidime-avibactam. Colonization with the same agents was detected in the surveillance ETA samples in 16.6% of the patients with K. pneumoniae and in 31.8% of those with P. aeruginosa. Before VAP, the most commonly used antibiotics were meropenem and piperacillin-tazobactam. While mortality was 83.4% in patients with K. pneumoniae, it was 95.5% in those with P. aeruginosa.
As indicated by the high resistance rate determined in carbapenem resistant P.aeruginosa isolates in our study, regular resistance follow-up is required for timely and effective use of ceftazidime-avibactam, one of the last-choice antibiotics, in severe infections used in ICU. In addition, surveillance ETA cultures are important in detecting colonization, in order to predict possible VAP causative microorganisms.
Keywords
carbapenem-resistant K. pneumoniae ventilator-associated pneumonia carbapenem-resistant P. aeruginosa ceftazidime/avibactam
References
- 1. Bassetti M, Mularoni A, Giacobbe DR, Castaldo N, Vena A. New antibiotics for hospital-acquired pneumonia and ventilator-associated pneumonia. Semin Respir Crit Care Med. 2022;43(2):280-94.
- 2. Bilgin M, Başbulut E, İşler H. Evaluation of the in vitro activity of ceftazidime-avibactam and ceftolozane-tazobactam against ceftazidime-resistant Pseudomonas aeruginosa isolates. FLORA 2021;26(4):713-9.
- 3. CDC. Magill SS, Klompas M, Balk R, et al. Developing a new, national approach to surveillance for ventilator-associated events: executive summary. Clin Infect Dis. 2013;57(12):1742-6.
- 4. Choi MH, Kim D, Lee KH, Cho JH, Jeong SH. Changes in the prevalence of pathogens causing hospital-acquired bacterial pneumonia and the impact of their antimicrobial resistance patterns on clinical outcomes: A propensity-score-matched study [published online ahead of print, 2023 Jun 19]. Int J Antimicrob Agents. 2023;62(3):106886.
- 5. Duran N, Çeken N, Atik T. Bacteria isolated from endotracheal aspirate samples and antibiotic resistance rates: 5-year analysis. Turkiye Klinikleri J Med Sci. 2021;41(3):327-34.
- 6. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. Version 12.0.2022.Available:https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_12.0_Breakpoint_Tables.pdf
- 7. Gill CM, Aktaþ E, Alfouzan W, et al. The ERACE-PA Global Surveillance Program: Ceftolozane/tazobactam and ceftazidime/avibactam in vitro activity against a global collection of carbapenem-resistant Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis. 2021;40(12):2533-41.
- 8. Güzel M, Öcal D, Önder İT, Akdoğan D, Erdem GB, Akpınar O. Çeşitli klinik örneklerden izole edilen karbapenem dirençli Enterobacteriaceae izolatlarına karşı seftolozan-tazobaktam ve seftazidim-avibaktam kombinasyonlarının in vitro antimikrobiyal etkinliğinin karşılaştırılması. Konuralp Tıp Derg. 2022;14(1):75-80.
- 9. Hoşbul T, Aydoğan CN, Kaya S, Bedir O, Gümral R, Albay A. Karbapenem dirençli Klebsiella pneumoniae klinik izolatlarına karşı seftazidim-avibaktam ve kolistinin in vitro etkinliği. Mikrobiyol Bul. 2022;56(2):218-29.
- 10. Karatas M, Saylan S, Kostakoglu U, Yilmaz G. An assessment of ventilator-associated pneumonias and risk factors identified in the Intensive Care Unit. Pak J Med Sci. 2016;32(4):817-22.
- 11. Karlowsky JA, Bouchillon SK, El Mahdy Kotb R, Mohamed N, Stone GG, Sahm DF. In vitro activity of ceftazidime/avibactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa from Middle Eastern and African countries: ATLAS global surveillance programme 2015-18. JAC Antimicrob Resist. 2021;3(2):dlab067.
- 12. Kempf M, Arhin FF, Stone G, Utt E. Ceftazidime-avibactam activity against Gram-negative respiratory isolates collected between 2018 and 2019. J Glob Antimicrob Resist. 2022;31:239-47.
- 13. KLİMUD. Tıbbi Mikrobiyoloji Uzmanları için Klinik Örnekten Sonuç Raporuna Uygulama Rehberi; solunum sistemi örnekleri. https://www.klimud.org/public/uploads/files/solunum-sistemi-ornekleri.pdf. (Erişim tarihi 3 Ocak 2022).
- 14. Koçak AA, Yayla B, Güçlü AÜ, Mirza HC, İştar EH, Alışkan HE, et al. Adana'da bir üniversite hastanesinde izole edilen solunum yolu patojenleri ve antibiyotik direnç profillerinin değerlendirilmesi. Türk Mikrobiyoloji Cem Derg. 2019;49(4):22632.
- 15. Meschiari M, Orlando G, Kaleci S, et al. Combined resistance to ceftolozane-tazobactam and ceftazidime-avibactam in extensively drug-resistant (XDR) and multidrug-resistant (MDR) Pseudomonas aeruginosa: Resistance predictors and impact on clinical outcomes besides implications for Antimicrobial Stewardship Programs. Antibiotics (Basel). 2021;10(10):1224.
- 16. Mirza HC, Hortaç E, Koçak AA, 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;20:334-38.
- 17. 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.
- 18. Pérez A, Gato E, Pérez-Llarena J, et al. High incidence of MDR and XDR Pseudomonas aeruginosa isolates obtained from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the magic bullet clinical trial. J Antimicrob Chemother. 2019;74(5):1244-52.
- 19. Ramadan RA, Bedawy AM, Negm EM, et al. Carbapenem-resistant Klebsiella pneumoniae among patients with ventilator-associated pneumonia: Evaluation of antibiotic combinations and susceptibility to new antibiotics. Infect Drug Resist. 2022;15:3537-48.
- 20. Spiliopoulou I, Kazmierczak K, Stone GG. In vitro activity of ceftazidime/avibactam against isolates of carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM global surveillance programme (2015–17). J Antimicrob Chemother. 2020;75(2):384-91.
- 21. Torrens G, van der Schalk TE, Cortes-Lara S, et al. Susceptibility profiles and resistance genomics of Pseudomonas aeruginosa isolates from European ICUs participating in the ASPIRE-ICU trial. J Antimicrob Chemother. 2022;77(7):1862-72.
- 22. Vo TPM, Dinh TC, Phan HV, Cao TTM, Duong PT, Nguyen T. Ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria in Vietnam: Antibiotic resistance, treatment outcomes, and colistin-associated adverse effects. Healthcare (Basel). 2022;10(9):1765.
- 23. Yesilbag Z, Tekdos Seker Y. Epidemiology and the risk factors for mortality in ventilator-associated pneumonia. Med J Bakirkoy. 2020;16(3):309-16.
- 24. Yin Y, Zhao C, Li H, et al. Clinical and microbiological characteristics of adults with hospital-acquired pneumonia: a 10-year prospective observational study in China. Eur J Clin Microbiol Infect Dis. 2021;40(4):683-90. 64
VENTİLATÖR İLİŞKİLİ PNÖMONİ ETKENİ KARBAPENEM DİRENÇLİ KLEBSIELLA PNEUMONIAE VE PSEUDOMONAS AERUGINOSA İZOLATLARINDA SEFTAZİDİM-AVİBAKTAMIN IN VITRO ETKİNLİĞİ
Abstract
Ventilatör ilişkili pnömoni (VİP), yoğun bakım ünitesi (YBÜ) kaynaklı en ciddi enfeksiyonlardan biridir. Bu çalışmanın amacı, hastanemizde VİP etkeni olarak izole edilmiş karbapenem dirençli Klebsiella pneumoniae ve Pseudomonas aeruginosa izolatlarına karşı seftazidim-avibaktamın in vitro etkinliğini saptamaktır. Endotrakeal aspirat (ETA) tarama örneklerinde etken mikroorganizma ile kolonizasyon sıklığı, VİP ile ilişkili risk faktörleri ve hasta sağ kalım sonuçlarının belirlenmesi de amaçlanmıştır.
Bu retrospektif çalışmaya, Eylül 2021- Aralık 2022 tarihleri arasında Haydarpaşa Numune Hastanesi YBÜ’nde yatan ve 48 saatten daha fazla mekanik ventilasyon desteği görmüş ve VİP tanısı almış hastalar ve ETA örnekleri dahil edildi. Suşların identifikasyonunda MALDI-TOF (VITEK-MS, bioMérieux, Fransa), antibiyotik duyarlılığının belirlenmesinde VITEK 2 otomatize sistemi (bioMérieux, Fransa) kullanıldı. Seftazidim-avibaktam duyarlılığı disk difüzyon yöntemi ile belirlenerek, dirençli bulunan suşlar ayrıca gradiyent difüzyon yöntemi (MIC strip, Liofilchem, İtalya) ile çalışıldı. Suşların antibiyotik duyarlılığı, European Committee on Antimicrobial Susceptibility Testing (EUCAST) kriterlerine göre değerlendirildi. Hastalara ait mikrobiyolojik veriler laboratuvar iletişim sistemi üzerinden, klinik bilgiler ise hastane iletişim sisteminde yer alan elektronik tıbbi kayıtlardan elde edildi.
Çalışmaya VIP gelişen ve örneklerinden karbapenem dirençli K. pneumoniae (n=18) ve P. aeruginosa (n=22) izole edilen 40 hasta dahil edildi. K. pneumoniae izolatlarının %22.2’si, P. aeruginosa izolatlarının ise %86.4’ü seftazidim-avibaktama dirençli bulundu. K. pneumoniae üremesi olan hastaların %16.6’sında, P. aeruginosa üremesi olanların %31.8’inde sürveyans ETA örneklerinde aynı etkenlerle kolonizasyon varlığı saptandı. VİP öncesi, en sık kullanılan antibiyotiklerin meropenem ve piperasilin-tazobaktam olduğu görüldü. K. pneumoniae üremesi olan hastalarda mortalite %83.4 iken, P. aeruginosa üremesi olanlarda %95.5 idi.
Çalışmamızda karbapenem dirençli P.aeruginosa izolatlarında belirlenen yüksek direnç oranının da işaret ettiği gibi, son seçenek antibiyotiklerden biri olan seftazidim- avibaktamın, ciddi enfeksiyonlarda zamanında ve etkin kullanımı için, düzenli direnç takibininin yapılması gereklidir. Ayrıca kolonizasyonu saptamada sürveyans ETA kültürlerinin alınması, olası VİP etkeni mikroorganizmaların önceden bilinmesi için önemlidir.
Keywords
karbapenem dirençli K. pneumoniae karbapenem dirençli P.aeruginosa seftazidim-avibactam ventilatör ilişkili pnömoni
References
- 1. Bassetti M, Mularoni A, Giacobbe DR, Castaldo N, Vena A. New antibiotics for hospital-acquired pneumonia and ventilator-associated pneumonia. Semin Respir Crit Care Med. 2022;43(2):280-94.
- 2. Bilgin M, Başbulut E, İşler H. Evaluation of the in vitro activity of ceftazidime-avibactam and ceftolozane-tazobactam against ceftazidime-resistant Pseudomonas aeruginosa isolates. FLORA 2021;26(4):713-9.
- 3. CDC. Magill SS, Klompas M, Balk R, et al. Developing a new, national approach to surveillance for ventilator-associated events: executive summary. Clin Infect Dis. 2013;57(12):1742-6.
- 4. Choi MH, Kim D, Lee KH, Cho JH, Jeong SH. Changes in the prevalence of pathogens causing hospital-acquired bacterial pneumonia and the impact of their antimicrobial resistance patterns on clinical outcomes: A propensity-score-matched study [published online ahead of print, 2023 Jun 19]. Int J Antimicrob Agents. 2023;62(3):106886.
- 5. Duran N, Çeken N, Atik T. Bacteria isolated from endotracheal aspirate samples and antibiotic resistance rates: 5-year analysis. Turkiye Klinikleri J Med Sci. 2021;41(3):327-34.
- 6. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. Version 12.0.2022.Available:https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_12.0_Breakpoint_Tables.pdf
- 7. Gill CM, Aktaþ E, Alfouzan W, et al. The ERACE-PA Global Surveillance Program: Ceftolozane/tazobactam and ceftazidime/avibactam in vitro activity against a global collection of carbapenem-resistant Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis. 2021;40(12):2533-41.
- 8. Güzel M, Öcal D, Önder İT, Akdoğan D, Erdem GB, Akpınar O. Çeşitli klinik örneklerden izole edilen karbapenem dirençli Enterobacteriaceae izolatlarına karşı seftolozan-tazobaktam ve seftazidim-avibaktam kombinasyonlarının in vitro antimikrobiyal etkinliğinin karşılaştırılması. Konuralp Tıp Derg. 2022;14(1):75-80.
- 9. Hoşbul T, Aydoğan CN, Kaya S, Bedir O, Gümral R, Albay A. Karbapenem dirençli Klebsiella pneumoniae klinik izolatlarına karşı seftazidim-avibaktam ve kolistinin in vitro etkinliği. Mikrobiyol Bul. 2022;56(2):218-29.
- 10. Karatas M, Saylan S, Kostakoglu U, Yilmaz G. An assessment of ventilator-associated pneumonias and risk factors identified in the Intensive Care Unit. Pak J Med Sci. 2016;32(4):817-22.
- 11. Karlowsky JA, Bouchillon SK, El Mahdy Kotb R, Mohamed N, Stone GG, Sahm DF. In vitro activity of ceftazidime/avibactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa from Middle Eastern and African countries: ATLAS global surveillance programme 2015-18. JAC Antimicrob Resist. 2021;3(2):dlab067.
- 12. Kempf M, Arhin FF, Stone G, Utt E. Ceftazidime-avibactam activity against Gram-negative respiratory isolates collected between 2018 and 2019. J Glob Antimicrob Resist. 2022;31:239-47.
- 13. KLİMUD. Tıbbi Mikrobiyoloji Uzmanları için Klinik Örnekten Sonuç Raporuna Uygulama Rehberi; solunum sistemi örnekleri. https://www.klimud.org/public/uploads/files/solunum-sistemi-ornekleri.pdf. (Erişim tarihi 3 Ocak 2022).
- 14. Koçak AA, Yayla B, Güçlü AÜ, Mirza HC, İştar EH, Alışkan HE, et al. Adana'da bir üniversite hastanesinde izole edilen solunum yolu patojenleri ve antibiyotik direnç profillerinin değerlendirilmesi. Türk Mikrobiyoloji Cem Derg. 2019;49(4):22632.
- 15. Meschiari M, Orlando G, Kaleci S, et al. Combined resistance to ceftolozane-tazobactam and ceftazidime-avibactam in extensively drug-resistant (XDR) and multidrug-resistant (MDR) Pseudomonas aeruginosa: Resistance predictors and impact on clinical outcomes besides implications for Antimicrobial Stewardship Programs. Antibiotics (Basel). 2021;10(10):1224.
- 16. Mirza HC, Hortaç E, Koçak AA, 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;20:334-38.
- 17. 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.
- 18. Pérez A, Gato E, Pérez-Llarena J, et al. High incidence of MDR and XDR Pseudomonas aeruginosa isolates obtained from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the magic bullet clinical trial. J Antimicrob Chemother. 2019;74(5):1244-52.
- 19. Ramadan RA, Bedawy AM, Negm EM, et al. Carbapenem-resistant Klebsiella pneumoniae among patients with ventilator-associated pneumonia: Evaluation of antibiotic combinations and susceptibility to new antibiotics. Infect Drug Resist. 2022;15:3537-48.
- 20. Spiliopoulou I, Kazmierczak K, Stone GG. In vitro activity of ceftazidime/avibactam against isolates of carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM global surveillance programme (2015–17). J Antimicrob Chemother. 2020;75(2):384-91.
- 21. Torrens G, van der Schalk TE, Cortes-Lara S, et al. Susceptibility profiles and resistance genomics of Pseudomonas aeruginosa isolates from European ICUs participating in the ASPIRE-ICU trial. J Antimicrob Chemother. 2022;77(7):1862-72.
- 22. Vo TPM, Dinh TC, Phan HV, Cao TTM, Duong PT, Nguyen T. Ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria in Vietnam: Antibiotic resistance, treatment outcomes, and colistin-associated adverse effects. Healthcare (Basel). 2022;10(9):1765.
- 23. Yesilbag Z, Tekdos Seker Y. Epidemiology and the risk factors for mortality in ventilator-associated pneumonia. Med J Bakirkoy. 2020;16(3):309-16.
- 24. Yin Y, Zhao C, Li H, et al. Clinical and microbiological characteristics of adults with hospital-acquired pneumonia: a 10-year prospective observational study in China. Eur J Clin Microbiol Infect Dis. 2021;40(4):683-90. 64
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Clinical Microbiology |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | August 31, 2023 |
| Published in Issue | Year 2023 Volume: 37 Issue: 2 |
Cited By
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