Molecular Investigation of Carbapenem and Colistin Resistance
Mechanisms in Klebsiella pneumoniae Bloodstream Isolates

Özcan, Nida; Gül, Kadri; KENAR, LEVENT; Atmaca, selahattin; Akpolat, Nezahat; altanlar, nurten; Kulahlioglu, Neslihan

Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates

Neslihan GENİŞEL, (Eczacılık Bilimleri Anabilim Dalı, Eczacılık Fakültesi, Dicle Üniversitesi, Diyarbakır, Türkiye)

Nida ÖZCAN, (Dicle Üniversitesi Tıp Fakültesi Tıbbi Mikrobiyoloji Anabilim Dalı, Diyarbakır, Türkiye)

Kadri GÜL, (Dicle Üniversitesi Tıp Fakültesi Tıbbi Mikrobiyoloji Anabilim Dalı, Diyarbakır, Türkiye)

Nezahat AKPOLAT, (Dicle Üniversitesi Tıp Fakültesi Tıbbi Mikrobiyoloji Anabilim Dalı, Diyarbakır, Türkiye)

Selahattin ATMACA, (Dicle Üniversitesi Tıp Fakültesi Tıbbi Mikrobiyoloji Anabilim Dalı, Diyarbakır, Türkiye)

Levent KENAR, (Tıbbi KBRN Savunma Anabilim Dalı, Sağlık Bilimleri Üniversitesi, Ankara, Türkiye)

Nurten ALTANLAR (Farmasötik Mikrobiyoloji Anabilim Dalı, Ankara Üniversitesi, Ankara, Türkiye)

FABAD Journal of Pharmaceutical Sciences

6 2

Yıl: 2021 Cilt: 46 Sayı: 3 Sayfa Aralığı: 289 - 298 Metin Dili: İngilizce İndeks Tarihi: 02-06-2022

Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates

Öz:

Carbapenem-Resistant Klebsiella pneumoniae (CRKp) infections are worrying health problems due to decreasing treatment options. This study investigates the carbapenemase (OXA-23,24, 48, 51, 55, 58, KPC, NDM-1, VIM, IMP) and mcr-1 genes of the CRKps isolates A total of 33 CRKp isolates isolated from patient blood samples from the Dicle University Medical Faculty Hospital, intensive care units (ICUs) between February 2020 and June 2020, were included in the study. The presence of carbapenemase encoding genes -including all CRKp isolates, bla OXA-23, 24, 48, 58, bla KPC, blaNDM-1, bla VIM, bla IMP- were investigated by multiplex Polymerase Chain Reaction (PCR). CRKp isolates were tested for mcr-1 gene and bla OXA-51, bla OXA-55 genes by monoplex PCR. All CRKp isolates studied with Kirby Bauer Disc Diffusion Method (DDM) (100%) were resistant to ertapenem, 9 (27.27%) resistant to imipenem, and 23 (69.70%) were resistant to meropenem. 20 (60.61%) of the isolates were found resistant to colistin. bla OXA-48, bla NDM-1 and bla OXA-24 genes were found in 75.76% (n = 25), 6.06% (n = 2) and 3.03% (n = 1) isolates, respectively. Both bla OXA-48 and bla NDM-1 genes were detected in two (6.06%) isolates and mcr-1 gene in 16 (48.48%) isolates. While the mean hospitalization was 20.3 days in 13 patients with a colistin minimum inhibitory concentration (MIC) of 2 μg/ml, it was 33.9 days in 20 patients with a colistin MIC of > 2 μg/ml. The average length of stay in the hospital was 21.8 days in mcr-1 negative patients and 35.7 days in mcr-1 positive patients. Carbapenemase and mcr-1 positivities were found at dramatically high rates in Diyarbakır, Turkey. It was indicated that plasmid-mediated antimicrobial resistance in Kp isolates was problematic. Each hospital should monitor the colistin and carbapenem resistance mechanisms by molecular methods. Colistin resistance should be confirmed by the broth microdilution method (BMD).

Anahtar Kelime:

Klebsiella Pneumoniae Kan İzolatlarında Karbapenem ve Kolistin Direnç Mekanizmalarının Moleküler Olarak İncelenmesi

Öz:

Karbapenem Dirençli Klebsiella pneumoniae (KDKp) enfeksiyonları azalan tedavi seçenekleri nedeniyle endişe verici sağlık sorunları oluşturmaktadır. Bu çalışmada, KDKp izolatlarının karbapenemaz (OXA-23,24, 48, 51, 55, 58, KPC, NDM-1, VIM, IMP) ve mcr-1 genleri araştırılmaktadır. Dicle Üniversitesi Tıp Fakültesi Hastanesi yoğun bakım ünitelerinden (YBÜ) Şubat 2020 ile Haziran 2020 tarihleri arasında alınan hasta kan örneklerinden izole edilen toplam 33 KDKp izolatı çalışmaya dahil edildi. Tüm KDKp izolatları, bla OXA-23, 24, 48, 58, bla KPC, blaNDM-1, bla VIM, bla IMP dahil olmak üzere karbapenemaz kodlayan genlerin varlığı multipleks Polimeraz Zincir Reaksiyonu (PZR) ile araştırıldı. KDKp izolatları monoplex PZR ile mcr- 1 geni ve bla OXA-51, bla OXA-55 genleri için test edildi. Kirby Bauer Disk Difüzyon Test (DDT) (%100) ile çalışılan tüm KDKp izolatları ertapenem’e dirençliydi; 9’u (%2.27) imipeneme, 23’ü (%69.70) meropeneme dirençliydi. İzolatların 20’si (%60,61) kolistine dirençli bulundu. bla OXA-48, bla NDM-1 ve bla OXA-24 genleri sırasıyla %75.76 (n=25), %6.06 (n=2) ve %3.03 (n=1) izolatında bulundu. İki (%6.06) izolatta hem bla OXA-48 hem de bla NDM-1 genleri, 16 (%48,48) izolatta mcr-1 geni saptandı. Kolistin minimum inhibitör konsantrasyonu (MİK) değeri 2 μg/ml olan 13 hastada ortalama yatış süresi 20.3 gün iken, kolistin MİK değeri > 2 μg/ml olan 20 hastada 33.9 gündü. Hastanede ortalama kalış süresi mcr-1 negatif hastalarda 21.8 gün, mcr-1 pozitif hastalarda 35.7 gündü. Karbapenemaz ve mcr- 1 pozitiflikleri Diyarbakır, Türkiye’de çarpıcı biçimde yüksek oranlarda bulundu. Kp izolatlarında plazmit aracılı antimikrobiyal direncin sorunlu olduğu belirtildi. Her hastane moleküler yöntemlerle kolistin ve karbapenem direnç mekanizmalarını izlemelidir. Kolistin direnci sıvı mikrodilüsyon yöntemi ile doğrulanmalıdır.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	Kulahlioglu N, Özcan N, Gül K, Akpolat N, Atmaca s, KENAR L, altanlar n (2021). Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. , 289 - 298.
Chicago	Kulahlioglu Neslihan,Özcan Nida,Gül Kadri,Akpolat Nezahat,Atmaca selahattin,KENAR LEVENT,altanlar nurten Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. (2021): 289 - 298.
MLA	Kulahlioglu Neslihan,Özcan Nida,Gül Kadri,Akpolat Nezahat,Atmaca selahattin,KENAR LEVENT,altanlar nurten Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. , 2021, ss.289 - 298.
AMA	Kulahlioglu N,Özcan N,Gül K,Akpolat N,Atmaca s,KENAR L,altanlar n Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. . 2021; 289 - 298.
Vancouver	Kulahlioglu N,Özcan N,Gül K,Akpolat N,Atmaca s,KENAR L,altanlar n Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. . 2021; 289 - 298.
IEEE	Kulahlioglu N,Özcan N,Gül K,Akpolat N,Atmaca s,KENAR L,altanlar n "Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates." , ss.289 - 298, 2021.
ISNAD	Kulahlioglu, Neslihan vd. "Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates". (2021), 289-298.

APA	Kulahlioglu N, Özcan N, Gül K, Akpolat N, Atmaca s, KENAR L, altanlar n (2021). Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. FABAD Journal of Pharmaceutical Sciences, 46(3), 289 - 298.
Chicago	Kulahlioglu Neslihan,Özcan Nida,Gül Kadri,Akpolat Nezahat,Atmaca selahattin,KENAR LEVENT,altanlar nurten Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. FABAD Journal of Pharmaceutical Sciences 46, no.3 (2021): 289 - 298.
MLA	Kulahlioglu Neslihan,Özcan Nida,Gül Kadri,Akpolat Nezahat,Atmaca selahattin,KENAR LEVENT,altanlar nurten Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. FABAD Journal of Pharmaceutical Sciences, vol.46, no.3, 2021, ss.289 - 298.
AMA	Kulahlioglu N,Özcan N,Gül K,Akpolat N,Atmaca s,KENAR L,altanlar n Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. FABAD Journal of Pharmaceutical Sciences. 2021; 46(3): 289 - 298.
Vancouver	Kulahlioglu N,Özcan N,Gül K,Akpolat N,Atmaca s,KENAR L,altanlar n Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates. FABAD Journal of Pharmaceutical Sciences. 2021; 46(3): 289 - 298.
IEEE	Kulahlioglu N,Özcan N,Gül K,Akpolat N,Atmaca s,KENAR L,altanlar n "Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates." FABAD Journal of Pharmaceutical Sciences, 46, ss.289 - 298, 2021.
ISNAD	Kulahlioglu, Neslihan vd. "Molecular Investigation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae Bloodstream Isolates". FABAD Journal of Pharmaceutical Sciences 46/3 (2021), 289-298.