Abstract：
Extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales as a cause of community-acquired uncomplicated urinary tract infection (UTI) is on the rise. Currently, there are minimal oral treatment options. New combinations of existing oral third-generation cephalosporins paired with clavulanate may overcome resistance mechanisms seen in these emerging uropathogens. Ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae containing CTX-M-type ESBLs or AmpC, in addition to narrow-spectrum OXA and SHV enzymes, were selected from blood culture isolates obtained from the MERINO trial. Minimum inhibitory concentration (MIC) values of third-generation cephalosporins (cefpodoxime, ceftibuten, cefixime, cefdinir), both with and without clavulanate, were determined. One hundred and one isolates were used with ESBL, AmpC and narrow-spectrum OXA genes (e.g. OXA-1, OXA-10) present in 84, 15 and 35 isolates, respectively. Susceptibility to oral third-generation cephalosporins alone was very poor. Addition of 2 mg/L clavulanate reduced the MIC50 values (cefpodoxime MIC50 2 mg/L, ceftibuten MIC50 2 mg/L, cefixime MIC50 2 mg/L, cefdinir MIC50 4 mg/L) and restored susceptibility (33%, 49%, 40% and 21% susceptible, respectively) in a substantial number of isolates. This finding was less pronounced in isolates co-harbouring AmpC. In-vitro activity of these new combinations may be limited in real-world Enterobacterales isolates co-harbouring multiple antimicrobial resistance genes. Pharmacokinetic/pharmacodynamic data would be useful for further evaluation of their activity.
摘要：
产超广谱β-内酰胺酶（ESBL）的肠杆菌是社区获得性单纯性尿路感染（UTI）的原因之一。目前,存在最少的口服治疗选择。现有的口服第三代头孢菌素与克拉维酸盐配对的新组合可以克服在这些新出现的尿路病原体中看到的耐药机制。含CTX-M型ESBLs或AmpC的耐头孢曲松大肠埃希菌和肺炎克雷伯菌,除了窄谱OXA和SHV酶，从MERINO试验获得的血液培养分离物中选择。第三代头孢菌素（头孢泊肟，头孢替丁,头孢克肟,测定了含有和不含克拉维酸的头孢地尼）。一百一十一株分离物与ESBL一起使用，AmpC和窄谱OXA基因（如OXA-1、OXA-10）存在于84、15和35个分离株中，分别。单独口服第三代头孢菌素的敏感性非常差。添加2mg/L克拉维酸会降低MIC50值（头孢泊肟MIC502mg/L，头孢替丁MIC502mg/L，头孢克肟MIC502mg/L，头孢地尼MIC504mg/L)和恢复的敏感性(33%，49%,40%,21%易感，分别)在大量的分离物中。这一发现在共携带AmpC的分离株中不太明显。这些新组合的体外活性可能在共同携带多个抗微生物抗性基因的真实世界肠杆菌分离物中受到限制。药代动力学/药效学数据可用于进一步评估其活性。
