Division of Clinical Infectious Diseases & Chemotherapy, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Department of Pharmacy, Sendai Medical Centergrid.415495.8, Sendai, Japan.
Microbiol Spectr. 2022 Jun 29;10(3):e0005822. doi: 10.1128/spectrum.00058-22. Epub 2022 Jun 6.
Cefazolin, an active agent against Escherichia coli, is used to treat urinary and biliary tract infections. Cefazolin is used widely as an antibiotic, and the increase in the emergence of cefazolin-resistant E. coli in many countries is a major concern. We investigated the changes in the susceptibility of E. coli clinical isolates to cefazolin following exposure. A total of 88.9% (16/18 strains) of the strains acquired resistance to cefazolin. All strains with an MIC to cefazolin of 2 μg/mL became resistant. The expression of chromosomal (c-) increased up to 209.1-fold in the resistant strains. Moreover, 11 of the 16 E. coli strains (68.8%) that acquired cefazolin resistance maintained the resistant phenotype after subculture in cefazolin-free medium. Therefore, the acquisition and maintenance of cefazolin resistance in E. coli strains were associated with the overexpression of c-. Mutations in the c- attenuator regions are likely to be maintained and are one of the key factors contributing to the increase in the number of cefazolin-resistant E. coli worldwide. This study is the first to demonstrate that mutations in the chromosomal-C attenuator region are responsible for the emergence of cefazolin resistance in Escherichia coli strains. The resistance was maintained even after culturing E. coli without cefazolin. This study highlights one of the key factors contributing to the increase in the number of cefazolin-resistant E. coli strains, which can pose a considerable challenge for treating common infections, such as urinary tract infections.
头孢唑林是一种针对大肠埃希菌的有效药物,用于治疗尿路感染和胆道感染。头孢唑林作为一种抗生素被广泛使用,许多国家头孢唑林耐药大肠埃希菌的出现增加令人担忧。我们研究了大肠埃希菌临床分离株在接触头孢唑林后对头孢唑林敏感性的变化。共有 16/18 株(88.9%)的菌株对头孢唑林产生了耐药性。所有 MIC 为 2μg/mL 的菌株均产生耐药性。耐药株中染色体(c-)的表达增加了 209.1 倍。此外,16 株大肠埃希菌中有 11 株(68.8%)在无头孢唑林培养基中传代后仍保持耐药表型。因此,大肠埃希菌菌株对头孢唑林的获得和维持耐药与 c-的过表达有关。c-衰减子区域的突变可能会被维持,是导致全球头孢唑林耐药大肠埃希菌数量增加的关键因素之一。本研究首次证明,染色体-C 衰减子区域的突变导致大肠埃希菌对头孢唑林的耐药性的出现。即使在没有头孢唑林的情况下培养大肠埃希菌,耐药性仍得以维持。本研究强调了导致头孢唑林耐药大肠埃希菌数量增加的关键因素之一,这可能对治疗常见感染(如尿路感染)构成相当大的挑战。