Thelen Haedi, Dilworth Thomas J, Mercier Renée-Claude
Department of Pharmacy Practice and Administrative Sciences, University of New Mexico College of Pharmacy, Albuquerque, New Mexico, USA.
Department of Pharmacy, Advocate Aurora Health Milwaukee, Milwaukee, Wisconsin, USA.
Chemotherapy. 2022;67(4):261-268. doi: 10.1159/000524707. Epub 2022 May 2.
Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have limited oral therapeutic options and pose significant clinical challenges. The goal of this study was to evaluate the in vitro synergy between CFM and AMC against ESBL E. coli with aims to identify an oral treatment option for UTIs.
Minimum inhibitory concentrations (MICs) of CFM in the presence of AMC were determined for 46 clinical isolates by placing a CFM Etest on a plate with AMC impregnated in the agar. Isolates with CFM MIC ≤1 μg/mL in the presence of AMC were considered susceptible to the CFM and AMC combination. Five isolates were then selected for further testing using time-kill analysis in the presence of CFM, AMC, and CFM with AMC. Time-kill curves were plotted to determine synergy over 24 h.
AMC improved the activity of CFM against ESBL E. coli isolates by 128-fold in the Etest analysis with 85% of tested isolates being susceptible to the combination. A fourfold or greater reduction in CFM MIC was exhibited in 44 of 46 (96%) isolates when in the presence of AMC. Synergy and bactericidal activity between CFM and AMC were exhibited in each of the five isolates tested by time-kill analysis.
DISCUSSION/CONCLUSION: This study found that AMC improves the activity of CFM against ESBL E. coli and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL E. coli UTIs.
由产超广谱β-内酰胺酶（ESBL）的大肠埃希菌引起的社区获得性尿路感染（UTIs），口服治疗选择有限，带来了重大的临床挑战。本研究的目的是评估头孢呋辛酯（CFM）和阿莫西林/克拉维酸（AMC）对产ESBL大肠埃希菌的体外协同作用，旨在确定一种UTIs的口服治疗方案。
通过将CFM Etest放置在琼脂中浸渍有AMC的平板上，测定46株临床分离株在AMC存在下CFM的最低抑菌浓度（MICs）。在AMC存在下CFM MIC≤1μg/mL的分离株被认为对CFM和AMC联合敏感。然后选择5株分离株，在CFM、AMC和CFM与AMC存在下使用时间杀菌分析进行进一步测试。绘制时间杀菌曲线以确定24小时内的协同作用。
在Etest分析中，AMC使CFM对产ESBL大肠埃希菌分离株的活性提高了128倍，85%的测试分离株对该联合敏感。在46株（96%）分离株中的44株中，当存在AMC时，CFM MIC降低了四倍或更多。通过时间杀菌分析测试的5株分离株中的每一株都表现出CFM和AMC之间的协同作用和杀菌活性。
讨论/结论：本研究发现，AMC提高了CFM对产ESBL大肠埃希菌的活性，并且这种抗生素联合有潜力作为治疗产ESBL大肠埃希菌UTIs的口服治疗选择。
