Deshpande Lalitagauri M, Doyle Timothy B, Sader Helio S, Castanheira Mariana
Element Iowa City (JMI Laboratories), North Liberty, IA, USA.
Element Iowa City (JMI Laboratories), North Liberty, IA, USA.
J Glob Antimicrob Resist. 2025 Jun 9;44:103-110. doi: 10.1016/j.jgar.2025.06.002.
Enterobacterales isolates producing β-lactamases are widespread and threaten the use of β-lactams. This study evaluated the activity of aztreonam-avibactam and comparator antimicrobial agents against Enterobacterales isolates producing common β-lactamases collected in US hospitals.
A total of 18,148 Enterobacterales isolates collected during 2020-2021 in US hospitals (n = 71) were susceptibility tested by reference broth microdilution methods. A total of 2,337 isolates were submitted to whole genome sequencing due to elevated cephalosporins/aztreonam MIC values or carbapenem nonsusceptibility (meropenem and/or imipenem MIC results at >1 mg/L).
ESBL enzymes were observed among 1,430 carbapenem-susceptible E. coli, K. pneumoniae, E. cloacae and Citrobacter spp. isolates and CTX-M-15 was the most common ESBL. Ceftazidime-avibactam inhibited all ESBL-producers while ceftolozane-tazobactam inhibited 68.4-95.9%. Aztreonam-avibactam inhibited >99.7% of the isolates regardless of the ESBL type or organism. Among other classes, amikacin and tigecycline were the most active agents, inhibiting 78.5% and 97.8% of the ESBL-producing isolates. All isolates carrying transferrable AmpC genes were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, and 98.1% susceptible to aztreonam-avibactam, but only 83.3% were susceptible to ceftolozane-tazobactam. Five isolates carried bla with a PBP3 insertion and they exhibited aztreonam-avibactam MICs ranging from 2 to 16 mg/L. Among carbapenemase-producers (n = 157), aztreonam-avibactam, ceftazidime-avibactam and meropenem-vaborbactam susceptibility rates were 98.7%, 81.5% and 79.6%. The only comparator displaying activity against these isolates was tigecycline (93.0% susceptible).
New β-lactam/β-lactamase inhibitors were active against common β-lactamase-producing isolates from US hospitals, including carbapenemase-producing isolates for which therapeutic options are limited. Aztreonam-avibactam was the most active agent against carbapenemase producers, including MBL-carrying isolates.
产β-内酰胺酶的肠杆菌科分离株广泛存在，对β-内酰胺类药物的使用构成威胁。本研究评估了氨曲南-阿维巴坦及对照抗菌药物对在美国医院收集的产常见β-内酰胺酶的肠杆菌科分离株的活性。
采用参考肉汤微量稀释法对2020年至2021年期间在美国71家医院收集的总共18148株肠杆菌科分离株进行药敏试验。由于头孢菌素/氨曲南最低抑菌浓度（MIC）值升高或对碳青霉烯类不敏感（美罗培南和/或亚胺培南MIC结果>1mg/L），共2337株分离株进行了全基因组测序。
在1430株对碳青霉烯类敏感的大肠埃希菌、肺炎克雷伯菌、阴沟肠杆菌和柠檬酸杆菌属分离株中观察到超广谱β-内酰胺酶（ESBL），CTX-M-15是最常见的ESBL。头孢他啶-阿维巴坦抑制所有产ESBL菌株，而头孢洛扎-他唑巴坦抑制率为68.4%-95.9%。无论ESBL类型或菌株如何，氨曲南-阿维巴坦抑制>99.7%的分离株。在其他类别中，阿米卡星和替加环素是活性最强的药物，分别抑制78.5%和97.8%的产ESBL分离株。所有携带可转移AmpC基因的分离株对头孢他啶-阿维巴坦和美罗培南-巴坦姆敏感，98.1%对氨曲南-阿维巴坦敏感，但仅83.3%对头孢洛扎-他唑巴坦敏感。5株分离株携带PBP3插入的bla基因，其氨曲南-阿维巴坦MIC值为2至16mg/L。在产碳青霉烯酶分离株（n=157）中，氨曲南-阿维巴坦、头孢他啶-阿维巴坦和美罗培南-巴坦姆的敏感率分别为98.7%、81.5%和79.6%。唯一对这些分离株有活性的对照药物是替加环素（敏感率93.0%）。
新型β-内酰胺/β-内酰胺酶抑制剂对来自美国医院的产常见β-内酰胺酶分离株有活性，包括产碳青霉烯酶分离株，而针对产碳青霉烯酶分离株的治疗选择有限。氨曲南-阿维巴坦是针对产碳青霉烯酶分离株（包括携带金属β-内酰胺酶的分离株）活性最强的药物。
