Drieux L, Brossier F, Sougakoff W, Jarlier V
INSERM, U655-LRMA, Faculté de Médecine Pierre et Marie Curie (site Pitié-Salpêtrière), Université Pierre et Marie Curie-Paris 6, Paris, France.
Clin Microbiol Infect. 2008 Jan;14 Suppl 1:90-103. doi: 10.1111/j.1469-0691.2007.01846.x.
Strains of Enterobacteriaceae producing an extended spectrum beta-lactamase have become a concern in medical bacteriology as regards both antimicrobial treatment and infection control in hospitals. Extended-spectrum beta-lactamase (ESBL) detection tests should accurately discriminate between bacteria producing these enzymes and those with other mechanisms of resistance to beta-lactams, e.g., broad-spectrum beta-lactamases, inhibitor-resistant beta-lactamases and cephalosporinase overproduction. Several phenotypic detection tests, based on the synergy between a third-generation cephalosporin and clavulanate, have been designed: the double-disk synergy test (DDST), ESBL Etests, and the combination disk method. These tests often need to be refined in order for them to detect an ESBL in some bacterial strains, such as those that also overproduce a cephalosporinase. The sensitivity of the DDST can be improved by reducing the distance between the disks of cephalosporins and clavulanate. The use of cefepime, a fourth-generation cephalosporin that is less rapidly inactivated by cephalosporinase than by ESBL, improves the detection of synergy with clavulanate when there is simultaneous stable hyperproduction of a cephalosporinase; alternatively, the cephalosporinase can be inactivated by performing phenotypic tests on a cloxacillin-containing agar. Some beta-lactamases can hydrolyse both third-generation cephalosporins and carbapenems, such as the metallo-beta-lactamases, which are not inhibited by clavulanate, but rather by EDTA. The production of an ESBL masked by a metallo-beta-lactamase can be detected by means of double inhibition by EDTA and clavulanate. Since extended-spectrum Ambler class D oxacillinases are weakly inhibited by clavulanate and not inhibited by EDTA, their detection is difficult in the routine laboratory.
产超广谱β-内酰胺酶的肠杆菌科菌株在医学细菌学领域已成为抗菌治疗和医院感染控制方面的一个关注点。超广谱β-内酰胺酶（ESBL）检测试验应能准确区分产生这些酶的细菌与具有其他β-内酰胺耐药机制的细菌，例如广谱β-内酰胺酶、抑制剂耐药β-内酰胺酶和头孢菌素酶过度产生。基于第三代头孢菌素与克拉维酸之间的协同作用，设计了几种表型检测试验：双纸片协同试验（DDST）、ESBL Etest和复合纸片法。为了能在某些细菌菌株（如那些也过度产生头孢菌素酶的菌株）中检测到ESBL，这些试验常常需要改进。通过缩短头孢菌素和克拉维酸纸片之间的距离，可以提高DDST的敏感性。使用头孢吡肟（一种第四代头孢菌素，其被头孢菌素酶灭活的速度比被ESBL灭活的速度慢），当同时存在头孢菌素酶稳定过度产生时，可改善与克拉维酸协同作用的检测；或者，通过在含氯唑西林的琼脂上进行表型试验可使头孢菌素酶失活。一些β-内酰胺酶可水解第三代头孢菌素和碳青霉烯类，如金属β-内酰胺酶，其不受克拉维酸抑制，而是受EDTA抑制。被金属β-内酰胺酶掩盖的ESBL的产生可通过EDTA和克拉维酸双重抑制来检测。由于超广谱安布勒D类苯唑西林酶受克拉维酸抑制较弱且不受EDTA抑制，在常规实验室中很难对其进行检测。
