氨曲南-阿维巴坦正在临床开发中,用于治疗碳青霉烯耐药肠杆菌(CRE)引起的感染。尤其是那些对最近批准的β-内酰胺酶抑制剂组合(BLIC)具有抗性的药物。我们评估了大量的CRE分离株,包括不易感染头孢他啶-阿维巴坦的人,美罗培南-瓦巴坦,和/或亚胺培南-莱巴坦。总的来说,2020-2022年,从西欧(W-EU)的64个医疗中心连续收集了24,580株肠杆菌分离株(1/患者),东欧(E-EU),拉丁美洲(LATAM),亚太地区(APAC)。其中,1,016(4.1%)为CRE。通过肉汤微量稀释测试分离物的敏感性。通过全基因组测序筛选CRE分离株的碳青霉烯酶基因。氨曲南-阿维巴坦抑制99.6%的CRE。头孢他啶-阿维巴坦,美罗培南-瓦巴坦,亚胺培南-莱巴坦对64.6%有活性,57.4%,和50.7%的CRE分离株,分别;大多数不敏感的分离株携带金属β-内酰胺酶。氨曲南-阿维巴坦对≥98.9%对这些BLIC不敏感的分离株有活性。这些BLIC的活动因地区而异,在W-EU中观察到最高的敏感率(头孢他啶-阿维巴坦为76.9%,美罗培南-伐巴坦72.5%,亚胺培南-阿维巴坦为63.8%)和亚太地区确定的最低敏感率(头孢他啶-阿维巴坦为39.9%,美罗培南-伐巴坦为37.8%,亚胺培南-莱巴坦为27.5%)。最常见的碳青霉烯酶类型总体上是KPC(占CREs的44.6%),NDM(29.9%),和OXA-48样(16.0%)。KPC在拉丁美洲(该地区的CRE的64.1%)和西欧(61.1%)占主导地位。MBL发生率在亚太地区最高(该地区占CREs的59.5%),其次是LATAM(34.0%),欧盟(28.9%),和欧盟(23.6%)。总之,氨曲南-阿维巴坦对头孢他啶-阿维巴坦耐药的CRE分离株表现出有效的活性,美罗培南-瓦巴坦,和/或不依赖于所产生的碳青霉烯酶的亚胺培南-释放巴坦。
BACKGROUND: Aztreonam-avibactam is under clinical development for treatment of infections caused by carbapenem-resistant Enterobacterales (CRE), especially those resistant to recently approved β-lactamase inhibitor combinations (BLICs).
OBJECTIVE: To evaluate a large collection of CRE isolates, including those non-susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam.
METHODS: Overall, 24 580 Enterobacterales isolates were consecutively collected (1/patient) in 2020-2022 from 64 medical centres located in Western Europe (W-EU), Eastern Europe (E-EU), Latin America (LATAM), and the Asia-Pacific region (APAC). Of those, 1016 (4.1%) were CRE. Isolates were susceptibility tested by broth microdilution. CRE isolates were screened for carbapenemase genes by whole genome sequencing.
RESULTS: Aztreonam-avibactam inhibited 99.6% of CREs at ≤8 mg/L. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam were active against 64.6%, 57.4%, and 50.7% of CRE isolates, respectively; most of the non-susceptible isolates carried metallo-beta-lactamases. Aztreonam-avibactam was active against ≥98.9% of isolates non-susceptible to these BLICs. The activity of these BLICs varied by region, with highest susceptibility rates observed in W-EU (76.9% for ceftazidime-avibactam, 72.5% for meropenem-vaborbactam, 63.8% for imipenem-relebactam) and the lowest susceptibility rates identified in the APAC region (39.9% for ceftazidime-avibactam, 37.8% for meropenem-vaborbactam, and 27.5% for imipenem-relebactam). The most common carbapenemase types overall were KPC (44.6% of CREs), NDM (29.9%), and OXA-48-like (16.0%). KPC predominated in LATAM (64.1% of CREs in the region) and W-EU (61.1%). MBL occurrence was highest in APAC (59.5% of CREs in the region), followed by LATAM (34.0%), E-EU (28.9%), and W-EU (23.6%).
CONCLUSIONS: Aztreonam-avibactam demonstrated potent activity against CRE isolates resistant to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam independent of the carbapenemase produced.