4th Department of Internal Medicine, University of Athens Medical School, 'Attikon' University General Hospital, Athens, Greece.
J Antimicrob Chemother. 2012 Oct;67(10):2424-8. doi: 10.1093/jac/dks215. Epub 2012 Jun 4.
Extended-spectrum β-lactamases (ESBLs) have emerged as an important mechanism of β-lactam resistance among community uropathogens. We characterized the ESBLs of a collection of Escherichia coli isolates recovered from outpatients with urinary tract infection during nationwide surveillance conducted from 2005 to 2006 in Greece, and evaluated the in vitro activity of mecillinam and mecillinam/clavulanate against them.
ESBLs were characterized with PCR and sequencing. In vitro interactions were evaluated with agar dilution with and without clavulanate (4 mg/L) using an inoculum of 10(4) or 10(6) cfu/spot as well as with time-kill methodology.
Among 48 ESBL producers, 47 (97.9%) were susceptible to mecillinam. CTX-M-type enzymes were produced by 87.2%, with CTX-M-3 being the most prevalent. SHV enzymes were found in 10.6%, VEB enzymes in 2.1%, TEM enzymes in 19.2% and OXA-type enzymes in 12.8%. Synergy with clavulanate was detected in 60.4% using the agar dilution method and in 43.8% using the time-kill methodology. An inoculum effect was detected in 64.6% of isolates, but this phenomenon was inverted and synergy was evidenced for 85.4% with clavulanate. When a high inoculum was used, 60.4% (29/48) were resistant to mecillinam, but 97.9% (47/48) were susceptible in the presence of clavulanate.
CTX-M-type enzymes were the most prevalent among ESBL-producing E. coli uropathogens in Greece. Mecillinam may be useful in uncomplicated cystitis caused by ESBL producers with low MICs. The addition of the inhibitor could improve and extend the activity of mecillinam, even in the setting of infection with a high bacterial inoculum, and merits clinical evaluation.
超广谱β-内酰胺酶（ESBLs）已成为社区尿路感染病原体中β-内酰胺类耐药的重要机制。我们对 2005 年至 2006 年期间在希腊进行的全国性监测中，从门诊尿路感染患者中分离的大肠杆菌进行了 ESBL 特征描述，并评估了美西林和美西林/克拉维酸对这些细菌的体外活性。
采用 PCR 和测序对 ESBL 进行鉴定。采用琼脂稀释法（含或不含克拉维酸[4mg/L]），使用 10（4）或 10（6）cfu/点的接种物，并采用时间杀伤法，对体外相互作用进行评估。
在 48 株 ESBL 产生菌中，47 株（97.9%）对美西林敏感。CTX-M 型酶的产生率为 87.2%，CTX-M-3 最为常见。SHV 酶的检出率为 10.6%，VEB 酶为 2.1%，TEM 酶为 19.2%，OXA 型酶为 12.8%。琼脂稀释法检测到协同作用的占 60.4%，时间杀伤法检测到协同作用的占 43.8%。在 64.6%的分离株中观察到接种物效应，但这种现象发生反转，加用克拉维酸时，85.4%的分离株表现出协同作用。当使用高接种物时，60.4%（29/48）对美西林耐药，但加用克拉维酸时，97.9%（47/48）对美西林敏感。
在希腊，产 ESBL 大肠埃希菌尿路感染病原体中，CTX-M 型酶最为常见。对于 MIC 值较低的 ESBL 产生菌引起的单纯性膀胱炎，美西林可能有用。添加抑制剂可改善和扩展美西林的活性，即使在感染细菌接种物较高的情况下也是如此，值得临床评估。
