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Enterobacteriaceae에 대한 β-Lactam제 감수성시험 기준 및 Extended-Spectrum β-Lactamase와 Carbapenemase 검출을 위한 전략

Strategies for Interpretive Standards of β-Lactams Susceptibility Testing and Identification of Extended-Spectrum β-Lactamases and Carbapenemases in Enterobacteriaceae

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초록

최근 CLSI와 EUCAST에서는 oxyimino-β-lactam제와 carbapenem제의 감수성 기준을 변경하였고 이로 인해 감수성시험 결과만으로 ESBL과 carbapenemase를 검출할 수 있기 때문에 ESBL이나 carbapenemase 검출시험은 치료 목적으로 시행할 필요가 없으며 단지 감염관리 목적으로만 시행할 것을 권고하였다. 여러 임상 증례와 함께 약동학과 동물실험 결과가 이와 같은 감수성지침의 변화를 뒷받침하고 있다. 그러나 CLSI와 EUCAST의 일부 oxyimino-β-lactam제와 carbapenem제의 기준에 차이가 있다. 특히 ceftazidime과 cefepime의 감수성 기준은 CLSI가 EUCAST에 비해 비교적 높게 설정되어 있다. 둘째, MIC가 낮은 ESBL 생성 또는 carbapenemase 생성 Enterobacteriaceae에 의한 감염에 cephalosporin제나 carbapenem제로 치료하는 것이 효과가 있다는 증례만큼 치료에 실패했다는 증례가 적지않게 보고되고 있다. 셋째, 일반적으로 시행하는 감수성시험은 연구용 시험에 비해 부정확하여 MIC가 1-8 μg/mL 정도의 차이를 보이게 된다. 결론적으로, ESBL과 carbapenemase 검출시험을 계속 시행하고 ESBL 또는 carbapenemase 생성균주 감염 시 대상 약제의 사용을 피하는 것이 신중한 전략이라고 판단된다.

Abstract

The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) have recently revised the susceptibility interpretive criteria of oxyimino-β-lactams and carbapenems for Enterobacteriaceae. According to the new criteria, susceptibility testing results are sufficient to detect extended-spectrum β-lactamases (ESBLs) and carbapenemases; it is not necessary to perform ESBL or carbapenemase detection tests for therapeutic purposes. Thus, it has been recommended that these related tests be performed only for infection control. These changes in the susceptibility guidelines are supported by some clinical cases and the results of pharmacodynamic and animal studies. However, differences still exist between the breakpoints established by the CLSI and EUCAST with regard to some oxyimino-β-lactam and carbapenem antibiotics, in particular, the breakpoints for ceftazidime and cefepime established by the CLSI are higher than those established by the EUCAST. Also, similar numbers of successful and unsuccessful cases have been reported regarding the use of cephalosporins or carbapenems in treating infections caused by low-minimal inhibitory concentration (MIC) ESBL-producers or low-MIC carbapenemase-producers. Finally, routine susceptibility test methods are not as accurate as research-purpose test methods, showing differences in MICs ranging approximately from 1 to 8 μg/mL. In conclusion, it is strategically prudent to continue to perform ESBL and carbapenemase detection tests and to avoid the use of the corresponding antimicrobial agents for the treatment of ESBL- or carbapenemase-producing bacterial infections.

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