新型β-内酰胺/β-内酰胺酶抑制剂组合在头孢他啶不敏感(CAZ-NS)和亚胺培南不敏感(IPM-NS)铜绿假单胞菌中的作用尚未完全阐明。这项研究评估了新型β-内酰胺/β-内酰胺酶抑制剂组合对铜绿假单胞菌临床分离株的体外活性,确定阿维巴坦是如何恢复头孢他啶活性的,并比较了头孢他啶-阿维巴坦(CZA)和亚胺培南-雷巴坦(IMR)对产KPC的铜绿假单胞菌的活性。CZA的高易感率相似,IMR,在中国11家医院的596株铜绿假单胞菌临床分离株中发现头孢洛赞-他唑巴坦(88.9%至89.8%),对头孢他啶的敏感率高于亚胺培南(73.5%对63.1%)。对于CAZ-NS和IPM-NS分离株,CZA的敏感率,头孢洛赞-他唑巴坦,IMR为61.5%(75/122),54.9%(67/122),和51.6%(63/122),分别。对于CAZ-NS,IPM-NS但CZA敏感的分离株,34.7%(26/75)携带获得性β-内酰胺酶,以KPC-2为主(n=19),45.3%(34/75)的染色体β-内酰胺酶ampC过表达。在仅携带KPC-2碳青霉烯酶的22株分离物中,对CZA和IMR的敏感性分别为86.4%(19/22)和9.1%(2/22),分别。值得注意的是,95%(19/20)的IMR非易感分离株具有oprD基因的失活突变。总之,CZA,头孢洛赞-他唑巴坦,IMR对铜绿假单胞菌表现出高活性,CZA比IMR对CAZ-NS和IPM-NS分离株以及产生KPC的铜绿假单胞菌更具活性。阿维巴坦克服了KPC-2酶和过表达的AmpC产生的头孢他啶抗性。重要性抗菌素耐药性的出现在全球范围内构成了一个特殊的挑战,以及具有“难以治疗”抗性的铜绿假单胞菌的概念(DTR-P.铜绿假单胞菌)被提议。这里,铜绿假单胞菌临床分离株对三种β-内酰胺酶抑制剂组合高度敏感,CZA,IMR,和头孢特洛赞-他唑巴坦.KPC-2酶和非功能性孔蛋白OprD的组合有助于铜绿假单胞菌的IMR抗性,在对抗产生KPC-2的铜绿假单胞菌方面,CZA比IMR更活跃。CZA对CAZ-NS和IPM-NS铜绿假单胞菌也显示出良好的活性,主要通过抑制KPC-2酶和过量产生的AmpC,支持临床使用CZA治疗由DTR-P引起的感染。铜绿假单胞菌.
The role of novel β-lactam/β-lactamase inhibitor combinations in ceftazidime-nonsusceptible (CAZ-NS) and imipenem-nonsusceptible (IPM-NS) Pseudomonas aeruginosa has not been fully elucidated. This study evaluated the in vitro activity of novel β-lactam/β-lactamase inhibitor combinations against Pseudomonas aeruginosa clinical isolates, determined how avibactam restored ceftazidime activity, and compared the activity of ceftazidime-avibactam (CZA) and imipenem-relebactam (IMR) against KPC-producing P. aeruginosa. Similar high susceptibility rates for CZA, IMR, and ceftolozane-tazobactam (88.9% to 89.8%) were found for 596 P. aeruginosa clinical isolates from 11 hospitals in China, and a higher susceptibility rate to ceftazidime than imipenem was observed (73.5% versus 63.1%). For CAZ-NS and IPM-NS isolates, susceptibility rates for CZA, ceftolozane-tazobactam, and IMR were 61.5% (75/122), 54.9% (67/122), and 51.6% (63/122), respectively. For CAZ-NS, IPM-NS but CZA-susceptible isolates, 34.7% (26/75) harbored acquired β-lactamases with KPC-2 predominant (n = 19), and 45.3% (34/75) presented overexpression of chromosomal β-lactamase ampC. Among 22 isolates carrying KPC-2 carbapenemase alone, susceptibility rates to CZA and IMR were 86.4% (19/22) and 9.1% (2/22), respectively. Notably, 95% (19/20) of IMR-nonsusceptible isolates had an inactivating mutation of oprD gene. In conclusion, CZA, ceftolozane-tazobactam, and IMR exhibit high activity against P. aeruginosa, and CZA is more active than IMR against CAZ-NS and IPM-NS isolates as well as KPC-producing P. aeruginosa. Avibactam overcomes ceftazidime resistance engendered by KPC-2 enzyme and overexpressed AmpC. IMPORTANCE The emergence of antimicrobial resistance poses a particular challenge globally, and the concept of P. aeruginosa with \"difficult-to-treat\" resistance (DTR-P. aeruginosa) was proposed. Here, P. aeruginosa clinical isolates were highly susceptible to three β-lactamase inhibitor combinations, CZA, IMR, and ceftolozane-tazobactam. The combination of KPC-2 enzyme and nonfunctional porin OprD contributed to IMR resistance in P. aeruginosa, and CZA was more active than IMR in fighting against KPC-2-producing P. aeruginosa. CZA also showed good activity against CAZ-NS and IPM-NS P. aeruginosa, primarily by inhibiting KPC-2 enzyme and overproduced AmpC, supporting the clinical use of CZA in the treatment of infections caused by DTR-P. aeruginosa.