Servicio de Microbiología, Hospital Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.
Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0216121. doi: 10.1128/aac.02161-21. Epub 2022 Jan 10.
Novel β-lactam-β-lactamase inhibitor combinations currently approved for clinical use are poorly active against metallo-β-lactamase (MBL)-producing strains. We evaluated the activity of cefepime-taniborbactam (FTB [formerly cefepime-VNRX-5133]) and comparator agents against carbapenemase-producing ( = 247) and carbapenem-resistant Pseudomonas species ( = 170) clinical isolates prospectively collected from different clinical origins in patients admitted to 8 Spanish hospitals. FTB was the most active agent in both (97.6% MIC, ≤8/4 mg/L) and Pseudomonas (67.1% MIC, ≤8/4 mg/L) populations. The MIC was >8 mg/L in 6/247 (2.4%) isolates (3 KPC-producing Klebsiella pneumoniae isolates, 1 VIM-producing Enterobacter cloacae isolate, 1 IMP-producing E. cloacae isolate, and 1 NDM-producing Escherichia coli isolate) and in 56/170 (32.9%) Pseudomonas isolates, 19 of them carbapenemase producers (15 producers of VIM, 2 of GES, 1 of GES+VIM, and 1 of GES+KPC). Against the isolates with meropenem MICs of >2 mg/L (138/247), FTB was the most active agent against both serine-β-lactamases (107/138) and MBL producers (31/138) (97.2 and 93.5% MIC, ≤8/4 mg/L, respectively), whereas the activity of comparators was reduced, particularly against the MBL producers (ceftazidime-avibactam, 94.4 and 12.9%, meropenem-vaborbactam, 85.0 and 64.5%, imipenem-relebactam, 76.6 and 9.7%, ceftolozane-tazobactam, 1.9 and 0%, and piperacillin-tazobactam, 0 and 0%, respectively). Among the meropenem-resistant Pseudomonas isolates (163/170; MIC, >2 mg/L), the activities of FTB against serine-β-lactamase (35/163) and MBL (43/163) producers were 88.6 and 65.1%, respectively, whereas the susceptibilities of comparators were as follows: ceftazidime-avibactam, 88.5 and 16.0%, meropenem-vaborbactam, 8.5 and 7.0%, imipenem-relebactam, 2.9 and 2.3%, ceftolozane-tazobactam, 0 and 2.3%, and piperacillin-tazobactam, 0 and 0%, respectively. Microbiological results suggest FTB as a potential therapeutic option in patients infected with carbapenemase-producing and carbapenem-resistant Pseudomonas isolates, including MBL producers.
目前临床使用的新型β-内酰胺-β-内酰胺酶抑制剂组合对金属β-内酰胺酶（MBL）产生菌的活性较差。我们评估了头孢吡肟-他唑巴坦（FTB[前身为头孢吡肟-VNRX-5133]）和对照剂对来自西班牙 8 家医院不同临床来源的碳青霉烯酶产生的 （ = 247）和碳青霉烯耐药铜绿假单胞菌 （ = 170）临床分离株的活性。FTB 对两种细菌（97.6% MIC，≤8/4 mg/L）和铜绿假单胞菌（67.1% MIC，≤8/4 mg/L）的活性最高。6/247（2.4%）种 分离株（3 株产 KPC 的肺炎克雷伯菌分离株、1 株产 VIM 的阴沟肠杆菌分离株、1 株产 IMP 的阴沟肠杆菌分离株和 1 株产 NDM 的大肠埃希菌分离株）和 170 株铜绿假单胞菌分离株（32.9%）的 MIC 大于 8 mg/L，其中 19 株为碳青霉烯酶产生菌（15 株产生 VIM、2 株产生 GES、1 株产生 GES+VIM 和 1 株产生 GES+KPC）。对于美罗培南 MIC 值大于 2 mg/L 的 分离株（138/247），FTB 是针对两种丝氨酸-β-内酰胺酶（107/138）和 MBL 产生菌（31/138）的最有效药物（97.2 和 93.5% MIC，分别为≤8/4 mg/L），而对照剂的活性降低，特别是针对 MBL 产生菌（头孢他啶-阿维巴坦，94.4%和 12.9%，美罗培南-沃博巴坦，85.0%和 64.5%，亚胺培南-雷巴坦，76.6%和 9.7%，头孢唑肟-他唑巴坦，1.9%和 0%，哌拉西林-他唑巴坦，0%和 0%）。在美罗培南耐药铜绿假单胞菌分离株（163/170；MIC，>2 mg/L）中，FTB 对丝氨酸-β-内酰胺酶（35/163）和 MBL（43/163）产生菌的活性分别为 88.6%和 65.1%，而对照剂的药敏率如下：头孢他啶-阿维巴坦，88.5%和 16.0%，美罗培南-沃博巴坦，8.5%和 7.0%，亚胺培南-雷巴坦，2.9%和 2.3%，头孢唑肟-他唑巴坦，0%和 2.3%，哌拉西林-他唑巴坦，0%和 0%。微生物学结果表明，FTB 可能是治疗产碳青霉烯酶和耐碳青霉烯铜绿假单胞菌，包括 MBL 产生菌的感染患者的潜在治疗选择。
