Publication: Geniş spektrumlu beta laktamaz ve ampc beta laktamaz üreten escherichia coli ve klebsiella pneumoniae kökenlerinde karbapenemlere direnç ve mutant engelleme konsantrasyonunun belirlenmesi
Abstract
Genişlemiş spektrumlu beta laktamaz (GSBL) ve plazmid aracılı AmpC (pAmpC) beta laktamaz 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 ve/ veya pAmpC beta laktamaz üretiminin herhangi bir etkisinin olup olmadığının belirlenmesi amaçlanmıştır. Bu çalışmaya test grubu olarak, imipenem ve meropenem MİK=<1mg/ L olan, fenotipik ve genotipik yöntemlerle GSBL, pAmpC veya karbapenemaz enzimlerinden en az birine sahip olan (n:80) ve kontrol grubu olarak araştırılan enzimlerden hiçbirini içermeyen (n:19) Escherichia coli ve Klebsiella pneumoniae kökeni dahil edilmiştir. Kökenlerin imipenem, meropenem, ertapenem ve doripenem MİK ve MEK’leri agar dilüsyon yöntemiyle çalışılmıştır. GSBL(-) kökenlerin MEK90 değerleri duyarlı sınırlarda kalır iken, GSBL ve pAmpC üreten kökenlerde MEK90 değerleri 2-8µg/ ml kadar çıkmıştır. GSBL(+) kökenlerde karbapenem MEK değerleri GSBL(-) kökenlere kıyasla 2-9 dilüsyon daha yüksek bulunmuş ancak GSBL enzim türlerinin (TEM, SHV, CTX-M) bu dirence katkı açısından aralarında bir farklılık olmadığı saptanmıştır. Karbapenemaz üreten ama karbapenem MİK değeri duyarlı kategorisinde olan kökenlerin tamamı çok yüksek MEK90 değerleri (>256 µg/ ml) sergilemiştir. GSBL(+) kökenlerde imipenem ve meropenem 0,015-0,06 µg/ ml gibi çok düşük MİK değerlerinde bile yaklaşık %50 oranında mutant seçimine neden olmaktadır. Bu verilere göre; i) Köken karbapenem duyarlı olsa da GSBL ve pAmpC üretimi karbapenem dirençli mutant seçimine neden olmaktadır. ii) Karbapenemaz üreten kökenlerde karbapenem MİK değeri duyarlı olmasına rağmen tedavide başarısızlık olma olasılığı oldukça yüksektir. iii) Doripenem ve ertapenem en az, imipenem ve meropenem en fazla mutant seçen karbapenemlerdir. Mutant Engelleme Konsantrasyonu (MEK), Karbapenem Direnci.
Determination of Carbapenem Resistance and Mutant Prevention Concentration Escherichia coli and Klebsiella pneumoniae strains Producing Extended Spectrum Beta Lactamases and AmpC Beta Lactamases. Carbapenem usage has increased in treatment of infections caused by ESBL and plasmid mediated AmpC (pAmpC) beta lactamase producing Enterobacteriaceae. This practice has resulted in emergence of carbapenem resistance. Therefore, this study aimed to determine mutant prevention concentrations of carbapenems and resistance development during carbapenem treatment of infections due to ESBL and/ or pAmpC beta-lactamase producing bacteria. Among the Escherichia coli and Klebsiella pneumoniae isolates having imipenem and meropenem MIC=<1mg/ L and producing at least one of ESBL, pAmpC or carbapenemase enzymes (n:80) as test group and, isolates negative for all tested enzymes as control group have been included in this study. Imipenem, meropenem, doripenem, ertapenem MIC and MPC values were determined by agar dilution method for tested organisms. MPC90 values were still in susceptible range for ESBL(-) isolates however, MPC90 values increased to 2-8 mg/ L for ESBL(+) and pAmpC(+) isolates. MPC values were higher as 2 to 9 dilutions in ESBL producing strains compared to non-ESBL strains but mutant selection rate was not affected by any of ESBL enzymes (TEM, SHV, CTX-M). All strains that were carbapenemase producer but having MICs in susceptible category for carbapenems demonstrated very high MPCs(>256 µg/ ml). In ESBL(+) strains, imipenem and meropenem even in very low MICs (0,015-0,06 µg/ ml) have selected carbapenem resistant mutants in a rate of 50%. According to the results of this study, i) ESBL and pAmpC production bring about selection of carbapenem resistant mutants even though strains are carbapenem susceptible in routine tests, ii) Infections caused by strains with carbapenem MICs in susceptible range but producing carbapenemase may have high probability of treatment failure, iii) Among carbapenems, doripenem and ertapenem have the least imipenem and meropenem have the most potential for mutant selection. Mutant Prevention Concentration (MPC), Carbapenem Resistance.
Determination of Carbapenem Resistance and Mutant Prevention Concentration Escherichia coli and Klebsiella pneumoniae strains Producing Extended Spectrum Beta Lactamases and AmpC Beta Lactamases. Carbapenem usage has increased in treatment of infections caused by ESBL and plasmid mediated AmpC (pAmpC) beta lactamase producing Enterobacteriaceae. This practice has resulted in emergence of carbapenem resistance. Therefore, this study aimed to determine mutant prevention concentrations of carbapenems and resistance development during carbapenem treatment of infections due to ESBL and/ or pAmpC beta-lactamase producing bacteria. Among the Escherichia coli and Klebsiella pneumoniae isolates having imipenem and meropenem MIC=<1mg/ L and producing at least one of ESBL, pAmpC or carbapenemase enzymes (n:80) as test group and, isolates negative for all tested enzymes as control group have been included in this study. Imipenem, meropenem, doripenem, ertapenem MIC and MPC values were determined by agar dilution method for tested organisms. MPC90 values were still in susceptible range for ESBL(-) isolates however, MPC90 values increased to 2-8 mg/ L for ESBL(+) and pAmpC(+) isolates. MPC values were higher as 2 to 9 dilutions in ESBL producing strains compared to non-ESBL strains but mutant selection rate was not affected by any of ESBL enzymes (TEM, SHV, CTX-M). All strains that were carbapenemase producer but having MICs in susceptible category for carbapenems demonstrated very high MPCs(>256 µg/ ml). In ESBL(+) strains, imipenem and meropenem even in very low MICs (0,015-0,06 µg/ ml) have selected carbapenem resistant mutants in a rate of 50%. According to the results of this study, i) ESBL and pAmpC production bring about selection of carbapenem resistant mutants even though strains are carbapenem susceptible in routine tests, ii) Infections caused by strains with carbapenem MICs in susceptible range but producing carbapenemase may have high probability of treatment failure, iii) Among carbapenems, doripenem and ertapenem have the least imipenem and meropenem have the most potential for mutant selection. Mutant Prevention Concentration (MPC), Carbapenem Resistance.