產生Carbapenemase腸內菌屬之流行概況與感管措施

Carbapenemase-producing Enterobacteriaceae

Carbapenem類後線抗生素目前正面臨挑戰。Carbapenem抗藥性的機轉包括blaAmpC過度表現、extended spectrum –lactamase（ESBL）合併膜蛋白改變、以及carbapenemase的製造。如同其他的抗藥基因，製造carbapenemase的基因相信存在已久，可根據Ambler分類分為class A、B、D，亦可根據Bush-Jacoby的功能分類分為class 2d、2df、2f、3a、3b。目前carbapenemase相關基因已超過100種，根據功能分類的不同特性，對於單一carbapenemase抗藥基因菌株，實驗室可合併使用EDTA、clavulanic acid的反應，或根據該菌對oxacillin、aztreonam等的表現型（phenotypic type）作簡單的歸類，實際的抗藥基因型仍須仰類分生方法（如PCR、基因定序等）及IEF測PI值來確認。由於細菌可由plasmid、integron傳遞得到抗藥基因，使抗藥性的表現更複雜多元，並增加實驗室的判讀及分類的困難度。經統計顯示許多Carbapenemase基因由腸內菌數鑑定出，使得carbapenemase-producing Enterobactericeae成為感染管制的重要課題。發現菌株、主動篩檢具危險因子之相關單位，病人與醫療照護人員、擬定嚴謹的感管計畫等，皆屬防治計畫之一環。抗生素大量使用引發的篩選壓力為抗藥菌散佈的源頭，知易行難則是抗生素管理的現實寫照，期待藉由合理的抗生素管理計畫來延緩抗藥菌的散佈與流行。

Presently, carbapenems are one of the last lines of defense, but their effective use is now under threat. The mechanisms of carbapenem resistance include hyper-production of AmpC, ESBL production with porin alteration, and carbapenemase production. Carbapenemase-encoding genes, similar to other drug-resistance genes, have existed since long. According to the Ambler classification of β-lactamases, these genes are categorized as A, B, or D class genes. Moreover, according to the updated Bush-Jacoby functional classification, they are classified as the groups 2df, 2f, 3a, and 3b. Theoretically, laboratory tests can help identify the specific mechanism involved in carbapenem resistance by evaluating either their specific response to EDTA and clavulanic acid or their phenotypic response to monobactam and oxacillin. Further highly technical methods such as PCR are needed to accurately identify such carbapenem-resistant strains. However, in reality, drug-resistant phenotypes and their clinical responses are complicated as these strains obtain the drug-resistance genes from plasmids or integrons, making their clinical identification more difficult. Furthermore, blaKPC-2 was found to be associated with a transposon (Tn4401), and this increases the probability of spreading resistance genes. To date, more than 100 carbapenemase-encoding genes have been isolated and identified. Previous statistical resources reveal that numerous carbapenemase-encoding genes have been isolated from Enterobacteriaceae members and Klebsiella pneumoniae. This shows that the study of carbapenemase-producing Enterobacteriaceae is important in preventing the spread of drug-resistant genes. A prevention strategy should be based on finding resistant strains, screening probable high-risk groups, and adopting a well-knit antibiotic stewardship program. Undoubtedly, selection pressures exerted by antibiotic overuse increases the chances of developing drug resistance. For most clinicians, however, the reasonable use of antibiotics is difficult to achieve. Hopefully, there will be a suitable antibiotic stewardship program to ease the current conditions.