Sevinç BABA, Zerrin AKTAŞ, Mustafa Oral ÖNCÜL

KARBAPENEMLERE DİRENÇLİ KLEBSİELLA PNEUMONİAE İZOLATLARININ APRAMİSİNE DUYARLILIKLARININ ARAŞTIRILMASI

Amaç: Bu çalışmada, çeşitli klinik örneklerden izole edilen karbapenemlere dirençli Klebsiella pneumoniae izolatlarında blaOXA-48 benzeri, blaCTX-M-15, blaNDM-1 genlerinin varlığı ve apramisine duyarlılıklarının araştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışmaya Haziran-Eylül 2020 tarihleri arasında İstanbul Tıp Fakültesi Hastanesinde yatan hastalara ait çeşitli klinik örneklerden izole edilen 12 çoğul dirençli K. pneumoniae izolatı dahil edilmiştir. Bu izolatlarda imipenem, meroperem, ertapenem ve apramisin için minimum inhbisyon konsantrasyon (MİK) değerleri, EUCAST önerilerine göre sıvı mikrodilüsyon yöntemiyle saptanmıştır. Antibiyotik konsantrasyonları EUCAST (imipenem, meropenem, ertapenem) ve NARMS (apramisin) klinik sınır değerlerini kapsayacak şekilde <0,016-256 μg/mL olarak belirlenmiştir. Klasik polimeraz zincir reaksiyonu (PCR) yöntemiyle K. pneumoniae izolatlarında blaOXA-48, blaNDM-1, blaCTX-M-15 genlerinin varlığı araştırılmıştır. Bulgular: Karpanenemlere dirençli K. pneumoniae izolatlarının tamamında (n=12) blaOXA-48 benzeri ve blaCTX-M-15 genleri, bir izolatta (%8,33) blaNDM-1 geni saptanmıştır. İzolatlarının tümü ertapeneme, %91,7’si meropeneme ve %58,3’ü imipeneme dirençli bulunmuştur. Tüm izolatların apramisine duyarlı olduğu belirlenmiştir. MİK aralığı ertapenem için 4-256 μg/mL, meropenem için 0,5-64 μg/mL, imipenem için 0,5-128 μg/mL, apramisin için <0,016-2 μg/mL aralığında saptanmıştır. Sonuç: K. pneumoniae izolatlarında apramisin için düşük MİK değerlerinin saptanması, karbapenemlere veya tüm antibiyotiklere dirençli izolatlarda, tedavide alternatif olarak kullanılabilecek bir ajan olabileceğini düşündürmektedir. Bu nedenle apramisinin klinikte kullanılabilmesiyle ilgili daha kapsamlı çalışmalara ihtiyaç duyulmaktadır.

Anahtar Kelimeler:

Klebsiella pneumoniae, karbapenemler, apramisin, OXA-48, NDM-1, CTX-M-15

INVESTIGATION OF THE SUSCEPTIBILITY OF CARBAPENEMRESISTANT KLEBSIELLA PNEUMONIAE ISOLATES TO APRAMYCIN

Objective: In this study, it was aimed to investigate the presence of blaOXA-48- like, blaCTX-M-15, blaNDM-1 genes and susceptibility to apramycin of carbapenemresistant Klebsiella pneumoniae isolates isolated from various clinical samples. Material and Methods: Twelve multiple resistant K. pneumoniae isolates isolated from various clinical samples of hospitalized patients in Istanbul Faculty of Medicine Hospital between June and September 2020 were included in the study. The minimum inhibitory concentration (MIC) values for imipenem, meroperem, ertapenem and apramycin in these isolates were determined using the broth microdilution method according to EUCAST recommendations. The antibiotic concentrations were determined as <0.016-256 μg/mL, including the clinical breakpoints of EUCAST (imipenem, meropenem, ertapenem) and NARMS (apramycin). The presence of blaOXA-48, blaNDM-1, blaCTX-M-15 genes in K. pneumoniae isolates was investigated using the classical polymerase chain reaction (PCR) method. Results: The blaOXA-48-like and blaCTX-M-15 genes were detected in all isolates (n=12) of K. pneumoniae resistant to carbapenems, and the blaNDM-1 gene was found in one (8.33%). All isolates were found to be resistant to ertapenem, 91.7% of meropenem, 58.3% of imipenem. All isolates were determined as being susceptible to apramycin. The MIC values were detected between 4-256 μg/mL for ertapenem, 0.5-64 μg/mL for meropenem, 0.5-128 μg/mL for imipenem, and <0.016-2 μg/mL for apramycin. Conclusion: The detection of low MIC values for apramycin in K. pneumoniae isolates suggests that it may be an alternative treatment agent for isolates resistant to carbapenems or all antibiotics. Therefore, there is a need for more comprehensive studies on the clinical use of apramycin.

Keywords:

Klebsiella pneumoniae, Carbapenems, Apramycin, OXA-48, NDM-1, CTX-M-15,

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