Department of Molecular Medicine, University of Padova, 35122 Padova, Italy.
IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40135 Bologna, Italy.
Cells. 2024 Aug 6;13(16):1315. doi: 10.3390/cells13161315.
We investigated the activity of cefiderocol/β-lactamase inhibitor combinations against clinical strains with different susceptibility profiles to cefiderocol to explore the potentiality of antibiotic combinations as a strategy to contain the major public health problem of multidrug-resistant (MDR) pathogens. Specifically, we evaluated the synergistic activity of cefiderocol with avibactam, sulbactam, or tazobactam on three of the most "Critical Priority" group of MDR bacteria (carbapenem-resistant , , and ). Clinical isolates were genomically characterized by Illumina iSeq 100. The synergy test was conducted with time-kill curve assays. Specifically, cefiderocol/avibactam, /sulbactam, or /tazobactam combinations were analyzed. Synergism was assigned if bacterial grow reduction reached 2 log CFU/mL. We reported the high antimicrobial activity of the cefiderocol/sulbactam combination against carbapenem-resistant , , and ; of the cefiderocol/avibactam combination against carbapenem-resistant ; and of the cefiderocol/tazobactam combination against carbapenem-resistant and Our results demonstrate that all β-lactamase inhibitors (BLIs) tested are able to enhance cefiderocol antimicrobial activity, also against cefiderocol-resistant isolates. The cefiderocol/sulbactam combination emerges as the most promising combination, proving to highly enhance cefiderocol activity in all the analyzed carbapenem-resistant Gram-negative isolates, whereas the Cefiderocol/tazobactam combination resulted in being active only against carbapenem-resistant and and cefiderocol/avibactam was only active against carbapenem-resistant
我们研究了头孢地尔/β-内酰胺酶抑制剂组合对具有不同头孢地尔敏感性谱的临床菌株的活性，以探索抗生素组合作为控制多药耐药（MDR）病原体这一主要公共卫生问题的潜力。具体来说，我们评估了头孢地尔与阿维巴坦、舒巴坦或他唑巴坦对三种最“关键优先”组 MDR 细菌（耐碳青霉烯的、和）的协同活性。临床分离株通过 Illumina iSeq 100 进行基因组特征分析。协同试验采用时间杀伤曲线测定法进行。具体分析了头孢地尔/阿维巴坦、/舒巴坦或/他唑巴坦组合。如果细菌减少达到 2 对数 CFU/mL，则认为具有协同作用。我们报告了头孢地尔/舒巴坦组合对耐碳青霉烯的、和的高抗菌活性；头孢地尔/阿维巴坦组合对耐碳青霉烯的的高抗菌活性；以及头孢地尔/他唑巴坦组合对耐碳青霉烯的和的高抗菌活性。我们的结果表明，所有测试的β-内酰胺酶抑制剂（BLIs）都能够增强头孢地尔的抗菌活性，甚至对头孢地尔耐药株也有增强作用。头孢地尔/舒巴坦组合是最有前途的组合，证明在所有分析的耐碳青霉烯阴性革兰氏阴性菌分离株中高度增强了头孢地尔的活性，而头孢地尔/他唑巴坦组合仅对耐碳青霉烯的和有活性，头孢地尔/阿维巴坦仅对耐碳青霉烯的有活性。
