i̇st tıp fak derg Journal of Istanbul Faculty of Medicine 1305-6441 Istanbul University 10.26650/IUITFD.1092556 Health Care Administration Sağlık Kurumları Yönetimi IN VITRO ACTIVITY OF CEFTAZIDIME-AVIBACTAM AND COLISTIN AGAINST CARBAPENEM-RESISTANT PSEUDOMONAS AERUGINOSA CLINICAL ISOLATES SEFTAZİDİM-AVİBAKTAM VE KOLİSTİNİN KARBAPENEM DİRENÇLİ PSEUDOMONAS AERUGİNOSA KLİNİK İZOLATLARINA KARŞI İN VİTRO AKTİVİTESİ https://orcid.org/0000-0002-0150-4417 Hoşbul Tuğrul SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, GÜLHANE TIP FAKÜLTESİ, GÜLHANE TIP PR. (ANKARA) https://orcid.org/0000-0002-6081-8934 Aydogan Canset Nur SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, GÜLHANE TIP FAKÜLTESİ, GÜLHANE TIP PR. (ANKARA) https://orcid.org/0000-0003-3911-5342 Kaya Sinem Sağlık Bilimleri Üniversitesi Gülhane Eğitim ve Araştırma Merkezi https://orcid.org/0000-0002-9438-4011 Bedir Orhan SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, GÜLHANE TIP FAKÜLTESİ, GÜLHANE TIP PR. (ANKARA) https://orcid.org/0000-0003-0978-7906 Özcan Hande SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, GÜLHANE TIP FAKÜLTESİ, GÜLHANE TIP PR. (ANKARA) https://orcid.org/0000-0002-2303-8234 Gümral Ramazan SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, GÜLHANE TIP FAKÜLTESİ, GÜLHANE TIP PR. (ANKARA) 07 06 2022 85 3 355 361 03 24 2022 05 09 2022 Copyright © 1916, Journal of Istanbul Faculty of Medicine 1916 Journal of Istanbul Faculty of Medicine

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.

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.

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