Department of Pathology, Microbiology and Immunology, Division of Laboratory Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA.
Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0069324. doi: 10.1128/aac.00693-24. Epub 2024 Aug 19.
Treatment options for carbapenem-resistant gram-negative bacilli (CR-GNB), especially metallo-β-lactamase (MBL)-producing CR-GNB, are limited. Aztreonam (ATM) in combination with avibactam (AVI) has shown potential for treating MBL-producing carbapenem-resistant Enterobacterales (CREs) and . However, data on ATM in combination with other β-lactamase inhibitors (BLIs) are limited. We performed a multicenter study to evaluate the activities of ATM in combination with AVI, vaborbactam (VAB), relebactam (REL), tazobactam (TAZ) as well as with their commercially available formulations against CREs and using broth microdilution. AVI restored ATM activity for MBL-producing CREs (ATM: 9.8% vs ATM-AVI: 78.0%) and (ATM: 0% vs ATM-AVI: 93.3%). REL also moderately restored activity of ATM in MBL-producing CREs (ATM: 9.8% vs ATM-REL: 42.7%) and (ATM: 0% vs ATM-REL: 68.9%). VAB and TAZ demonstrated very limited effect on the activity of ATM against CR-GNB evaluated. The combination of ATM with ceftazidime-AVI (CAZ-AVI) demonstrated maximum activity against CREs. Although ATM-CAZ-AVI is the most potent regimen available for CREs and , ATM-IMI-REL might be a reasonable alternative.
治疗碳青霉烯类耐药革兰氏阴性菌(CR-GNB),尤其是产金属β-内酰胺酶(MBL)的 CR-GNB 的选择有限。氨曲南(ATM)联合阿维巴坦(AVI)在治疗产 MBL 的碳青霉烯类耐药肠杆菌科(CRE)和 方面显示出了潜力。然而,关于 ATM 联合其他β-内酰胺酶抑制剂(BLIs)的数据有限。我们进行了一项多中心研究,以评估 ATM 联合 AVI、沃博巴坦(VAB)、雷利巴坦(REL)、他唑巴坦(TAZ)以及它们的市售制剂对 CRE 和 采用肉汤微量稀释法的 活性。AVI 恢复了产 MBL 的 CRE 对 ATM 的活性(ATM:9.8% vs ATM-AVI:78.0%)和 (ATM:0% vs ATM-AVI:93.3%)。REL 也适度恢复了产 MBL 的 CRE 中 ATM 的活性(ATM:9.8% vs ATM-REL:42.7%)和 (ATM:0% vs ATM-REL:68.9%)。VAB 和 TAZ 对 CR-GNB 评估的 ATM 活性显示出非常有限的作用。ATM 联合头孢他啶-阿维巴坦(CAZ-AVI)对 CRE 显示出最大的活性。尽管 ATM-CAZ-AVI 是针对 CRE 和 的最有效方案,但 ATM-IMI-REL 可能是一个合理的替代方案。