School of Biomedical Sciences, The University of Western Australia, 30 Stirling Hwy, Crawley, Perth, WA, 6009, Australia.
School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Sci Rep. 2022 Oct 7;12(1):16814. doi: 10.1038/s41598-022-21101-x.
Multidrug resistant (MDR) P. aeruginosa accounts for 35% of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF). The usefulness of β-lactam antibiotics for treating CF, such as carbapenems and later generation cephalosporins, is limited by the development of antibacterial resistance. A proven treatment approach is the combination of a β-lactam antibiotic with a β-lactamase inhibitor. New β-lactam/β-lactamase inhibitor combinations are available, but data are lacking regarding the susceptibility of MDR CF-associated P. aeruginosa (CFPA) to these new combination therapies. In this study we determined MIC values for three new combinations; imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), and ceftolozane-tazobactam (C/T) against MDR CFPA (n = 20). The MIC of I-R, CZA, and C/T was 64/4, 32/4, and 16/8 (all µg/mL), respectively. The susceptibility of isolates to imipenem was not significantly improved with the addition of relebactam (p = 0.68). However, susceptibility to ceftazidime was significantly improved with the addition of avibactam (p < 0.01), and the susceptibility to C/T was improved compared to piperacillin/tazobactam (p < 0.05) These data provide in vitro evidence that I-R may not be any more effective than imipenem monotherapy against MDR CFPA. The pattern of susceptibility observed for CZA and C/T in the current study was similar to data previously reported for non-CF-associated MDR P. aeruginosa.
耐多药（MDR）铜绿假单胞菌占囊性纤维化（CF）患者呼吸道样本中分离的铜绿假单胞菌的 35%。治疗 CF 的β-内酰胺类抗生素（如碳青霉烯类和新一代头孢菌素类）的有效性受到抗菌耐药性发展的限制。一种经过验证的治疗方法是将β-内酰胺类抗生素与β-内酰胺酶抑制剂联合使用。新的β-内酰胺/β-内酰胺酶抑制剂联合用药已经可用，但缺乏关于这些新联合疗法对 MDR CF 相关铜绿假单胞菌（CFPA）的敏感性的数据。在这项研究中，我们确定了三种新组合的 MIC 值；亚胺培南-雷巴他定（I-R）、头孢他啶-阿维巴坦（CZA）和头孢洛扎-他唑巴坦（C/T）对 MDR CFPA（n=20）的 MIC 值分别为 64/4、32/4 和 16/8（所有 µg/mL）。添加雷巴他定并没有显著改善分离株对亚胺培南的敏感性（p=0.68）。然而，添加阿维巴坦显著提高了对头孢他啶的敏感性（p<0.01），并且与哌拉西林/他唑巴坦相比，C/T 的敏感性得到了提高（p<0.05）。这些数据提供了体外证据表明，与亚胺培南单药治疗相比，I-R 对 MDR CFPA 可能没有任何更有效。在本研究中观察到的 CZA 和 C/T 的敏感性模式与以前报道的非 CF 相关 MDR 铜绿假单胞菌的数据相似。
