目的:评估目前和未来不同的治疗性β-内酰胺/β-内酰胺酶抑制剂(BL/BLI)替代品,即氨曲南-阿维巴坦,亚胺培南-莱巴坦,美罗培南-瓦巴坦,头孢吡肟-齐达巴坦,头孢吡肟-坦尼博巴坦,美罗培南-纳卡巴坦,和舒巴坦-杜洛巴坦对抗肠杆菌中对头孢地洛的敏感性或耐药性降低的临床分离株,鲍曼不动杆菌,还有铜绿假单胞菌.
方法:氨曲南的MIC值,氨曲南-阿维巴坦,头孢吡肟,头孢吡肟-坦尼博巴坦,头孢吡肟-齐达巴坦,亚胺培南,亚胺培南-莱巴坦,美罗培南,美罗培南-瓦巴坦,美罗培南-纳卡巴坦,舒巴坦-杜洛巴坦,和头孢地洛与BLI联合测定了67、9和11例临床肠杆菌,铜绿假单胞菌或鲍曼不动杆菌分离株,分别,显示头孢地洛的MIC值≥1mg/L如果不可用,根据EUCAST的相应β-内酰胺断点用于BL/BLI组合。
结果:对于肠杆菌,氨曲南的敏感率,头孢吡肟,亚胺培南,美罗培南为7.5%,0%,10.4%,10.4%,分别,虽然头孢吡肟-齐达巴坦的比例更高(91%),头孢地洛-齐达巴坦(91%),美罗培南-纳卡巴坦(71.6%),cefiderocol-nacubactam(74.6%),头孢地洛-坦尼博巴坦(76.1%),如预期。对于铜绿假单胞菌分离株,观察到亚胺培南-来巴坦的敏感性较高,塞菲德罗-齐达巴坦,和美罗培南-伐巴坦(所有组合为56%)。对于鲍曼不动杆菌分离株,在商业或开发中的BL/BLI组合中观察到较低的敏感性;然而,发现舒巴坦-杜洛巴坦和头孢地洛与某些BLIs相关时的高敏感性(70%)。
结论:含有Zidebartam和nacubactam的组合对多重耐药肠杆菌临床分离株具有显著的体外活性,对头孢地洛的敏感性降低。另一方面,亚胺培南-雷巴坦和美罗培南-伐巴坦对铜绿假单胞菌的敏感率最高。最后,舒巴坦-杜洛巴坦和头孢地洛与BLI联合使用是针对鲍曼不动杆菌测试分离株的唯一有效选择。
OBJECTIVE: To evaluate the different present and future therapeutic β-lactam/β-lactamase inhibitor (BL/BLI) alternatives, namely aztreonam-avibactam, imipenem-relebactam, meropenem-
vaborbactam, cefepime-zidebactam, cefepime-taniborbactam, meropenem-nacubactam, and sulbactam-durlobactam against clinical isolates showing reduced susceptibility or resistance to cefiderocol in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa.
METHODS: MIC values of aztreonam, aztreonam-avibactam, cefepime, cefepime-taniborbactam, cefepime-zidebactam, imipenem, imipenem-relebactam, meropenem, meropenem-
vaborbactam, meropenem-nacubactam, sulbactam-durlobactam, and cefiderocol combined with a BLI were determined for 67, 9, and 11 clinical Enterobacterales, P. aeruginosa or A. baumannii isolates, respectively, showing MIC values of cefiderocol being ≥1 mg/L. If unavailable, the respective β-lactam breakpoints according to EUCAST were used for BL/BLI combinations.
RESULTS: For Enterobacterales, the susceptibility rates for aztreonam, cefepime, imipenem, and meropenem were 7.5%, 0%, 10.4%, and 10.4%, respectively, while they were much higher for cefepime-zidebactam (91%), cefiderocol-zidebactam (91%), meropenem-nacubactam (71.6%), cefiderocol-nacubactam (74.6%), and cefiderocol-taniborbactam (76.1%), as expected. For P. aeruginosa isolates, the higher susceptibility rates were observed for imipenem-relebactam, cefiderocol-zidebactam, and meropenem-
vaborbactam (56% for all combinations). For A. baumannii isolates, lower susceptibility rates were observed with commercially or under development BL/BLI combos; however, a high susceptibility rate (70%) was found for sulbactam-durlobactam and when cefiderocol was associated to some BLIs.
CONCLUSIONS: Zidebactam- and nacubactam-containing combinations showed a significant in vitro activity against multidrug-resistant Enterobacterales clinical isolates with reduced susceptibility to cefiderocol. On the other hand, imipenem-relebactam and meropenem-
vaborbactam showed the highest susceptibility rates against P. aeruginosa isolates. Finally, sulbactam-durlobactam and cefiderocol combined with a BLI were the only effective options against A. baumannii tested isolates.