Genişlemiş Spektrumlu Beta Laktamaz Üreten Enterobacteriaceae’larda Mutant Engelleme Konsantrasyonunun Saptanması

Abstract

Amaç: Genişlemiş spektrumlu beta laktamaz (GSBL) üreten Enterobactericeae kökenleri ile gelişen enfeksiyonların tedavisinde karbapenemlerin sıklıkla kullanılması beraberinde karbapenem direnci gelişmesine neden olmuştur. Bu nedenle çalışmamızda karbapenemlerin mutant engelleme konsantrasyonlarının (MEK) saptanması ve tedavi sırasında gelişen dirence GSBL üretiminin herhangi bir etkisinin olup olmadığının belirlenmesi amaçlanmıştır.
Gereç ve Yöntem: Bu çalışmaya test grubu olarak, imipenem ve meropenem MİK=<1mg/L olan, fenotipik ve genotipik yöntemlerle GSBL enzimlerinden en az birine sahip olan (n=56) ve kontrol grubu olarak araştırılan enzimlerden hiçbirini içermeyen (n=19) Escherichia coli ve Klebsiella pneumoniae kökeni dahil edilmiştir. Kökenlerin imipenem, meropenem, ertapenem ve doripenem minimal inhibitör konsantrasyonları (MİK) ve mutant engelleme konsantrasyonları (MEK) agar dilüsyon yöntemiyle çalışılmıştır.
Bulgular: GSBL (-) kökenlerin MEK90 değerleri duyarlı sınırlarda kalır iken, GSBL üreten kökenlerde MEK90 değerleri 2-8μg/mL’ye kadar çıkmıştır. GSBL(+) kökenlerde karbapenem MEK değerleri GSBL(-) kökenlere kıyasla 2-9 kat daha yüksek bulunmuş ancak GSBL enzim türlerinin (TEM, SHV, CTX-M) bu dirence katkı açısından aralarında bir farklılık olmadığı saptanmıştır. GSBL(+) kökenlerde imipenem ve meropenem 0,015-0,06 μg/mL gibi çok düşük MİK değerlerinde bile yaklaşık %50 oranında mutant seçimine neden olmaktadır.
Sonuç: Bu verilere göre; i) Köken karbapenem duyarlı olsa da GSBL üretimi karbapenem dirençli mutant seçimine neden olabilir gibi gözükmektedir. ii) Doripenem ve ertapenem en az, imipenem ve meropenem en fazla mutant seçen karbapenemlerdir

Keywords

• GSBL
• Enterobacteriaceae
• Mutant Engelleme Konsantrasyonu
• Enterobacteriaceae

Determination of Mutant Prevention Concentration in Extended Spectrum Beta Lactamases Producing Enterobacteriaceae

Abstract

Objectives: The use of carbapenems for treating infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae has increased. Consequently, this practice has resulted in the emergence of carbapenem resistance. In this study, we aimed to determine mutant prevention concentrations (MPCs) of carbapenems and the development of carbapenem resistance in infections caused by ESBL-producing bacteria.
Material and Method: The test group included isolates of Escherichia coli and Klebsiella pneumonia that produced imipenem and meropenem minimum inhibitor concentration (MIC)=<1mg/L and at least one of the ESBL (n=56). Negatives isolates (n=19) for all tested enzymes comprised the control group. Carbapenems included in the study were imipenem, meropenem, doripenem, and ertapenem. The MIC and MPC values of these drugs were determined using the agar dilution method for all tested organisms.
Results: In ESBL-negative isolates, the MPC90 values were in the susceptible range. In contrast, in the ESBL positive isolates, MPC90 value increased to 2–8 mg/L. The MPC values were 2- to 9-fold higher in the ESBL-producing strains compared with the non-ESBL strains. However, the mutant selection rate was not affected by the ESBL enzymes types (TEM, SHV, and CTX-M). In ESBL-positive strains, imipenem and meropenem, even at very low MICs (0.015–0.06 µg/mL), showed selective carbapenem-resistant mutants at a rate of 50%.
Conclusion: Our results suggest the following conclusions. i) ESBL production seems to increase carbapenem resistance in mutant strains, even though these are carbapenem susceptible in routine tests. ii) Among carbapenems, doripenem and ertapenem have the least potential for mutant selection whereas imipenem and meropenem have the most potential. 

Keywords

• Mutant Prevention Concentration (MPC)
• ESBL
• Enterobacteriaceae
• Enterobacteriaceae

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