IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Service de Microbiologie, Hôpital Robert-Debré, AP-HP, Paris, France.
J Antimicrob Chemother. 2017 Jul 1;72(7):1911-1914. doi: 10.1093/jac/dkx087.
Mecillinam is recommended in France as a first-line treatment for lower urinary tract infections, due to the large increase in resistance of Escherichia coli to other oral treatments, such as co-trimoxazole or fluoroquinolones, its limited impact on faecal microbiota and its stability in the presence of numerous β-lactamases. However, we recently identified several mecillinam-resistant E. coli isolates with a high-level expression penicillinase (HEP) phenotype that merit further study.
We studied two isogenic clinical isolates from one patient (one susceptible to mecillinam and one resistant to mecillinam) by WGS to determine the mechanism of mecillinam resistance and compared it with other mecillinam-resistant E. coli . We evaluated the synergistic combination of amoxicillin/clavulanate and mecillinam using a simple test, suitable for daily laboratory practice, to determine the MIC of this combination.
We showed that the presence of an SNP in the promoter of the plasmidic TEM-1 β-lactamase gene is sufficient to confer resistance to mecillinam. This mechanism was present in 67% of HEP-phenotype E. coli tested. Combining mecillinam with amoxicillin/clavulanate abolished resistance, with an MIC compatible with clinical use. This association was not sensitive to the inoculum effect, in contrast to mecillinam alone.
An HEP phenotype can confer mecillinam resistance in vitro . This resistance is abolished, regardless of the inoculum, by combining mecillinam with amoxicillin/clavulanate, and can be easily tested in the laboratory. This combination may be used as an oral relay treatment of non-complicated pyelonephritis due to multiresistant E. coli strains.
由于大肠杆菌对其他口服治疗药物（如复方新诺明或氟喹诺酮类药物）的耐药性大幅增加，米西林作为下尿路感染的一线治疗药物在法国得到推荐，其对粪便微生物群的影响有限，并且在存在大量β-内酰胺酶时具有稳定性。然而，我们最近发现了几种高水平表达青霉素酶（HEP）表型的米西林耐药大肠杆菌分离株，值得进一步研究。
我们通过 WGS 研究了来自一名患者的两个同源临床分离株（一个对米西林敏感，一个对米西林耐药），以确定米西林耐药的机制，并将其与其他米西林耐药大肠杆菌进行比较。我们使用一种简单的适合日常实验室实践的测试来评估阿莫西林/克拉维酸与米西林的协同组合，以确定该组合的 MIC。
我们表明，质粒型 TEM-1 β-内酰胺酶基因启动子中的 SNP 的存在足以赋予米西林耐药性。这种机制存在于 67%的测试 HEP 表型大肠杆菌中。米西林与阿莫西林/克拉维酸联合使用可消除耐药性，MIC 与临床应用相容。与单独使用米西林不同，这种组合对接种物效应不敏感。
HEP 表型可在体外赋予米西林耐药性。无论接种物如何，米西林与阿莫西林/克拉维酸联合使用均可消除耐药性，并且可以在实验室中轻松测试。这种组合可能可用于治疗多耐药大肠杆菌引起的非复杂性肾盂肾炎的口服替代治疗。
