Al Musawa Mohammed, Bleick Callan R, Herbin Shelbye R, Caniff Kaylee E, Van Helden Sean R, Rybak Michael J
Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
John D. Dingell VA Medical Center, Detroit, Michigan, USA.
Pharmacotherapy. 2024 Dec;44(12):927-938. doi: 10.1002/phar.4629. Epub 2024 Nov 27.
Antimicrobial resistance poses a significant public health challenge, particularly with the rise of gram-negative hospital-acquired infections resistant to carbapenems. Aztreonam-avibactam (ATM-AVI) is a promising new combination therapy designed to combat multidrug-resistant (MDR) gram-negative bacteria, including those producing metallo-β-lactamases (MBLs). Aztreonam, a monobactam antibiotic, is resistant to hydrolysis by MBLs but can be degraded by other β-lactamases. Avibactam, a novel non-β-lactam β-lactamase inhibitor, effectively neutralizes extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases, restoring aztreonam's efficacy against resistant pathogens. This review covers the chemistry, mechanisms of action, spectrum of activity, pharmacokinetics, pharmacodynamics, and clinical efficacy of ATM-AVI. ATM-AVI combination has shown efficacy against a wide range of resistant Enterobacterales and other gram-negative bacteria in both in vitro and clinical studies. Pharmacokinetic and pharmacodynamic analyses demonstrate that ATM-AVI maintains effective drug concentrations in the body, with dose adjustments recommended for patients with renal impairment. Clinical trials, including the REVISIT and ASSEMBLE studies, have demonstrated the safety and efficacy of ATM-AVI in treating complicated intra-abdominal infections (cIAI), urinary tract infections (UTIs), and hospital-acquired pneumonia (HAP) caused by MDR gram-negative pathogens. The European Medicines Agency (EMA) has approved ATM-AVI for these indications, and further research is ongoing to optimize dosing regimens and expand its clinical use. This combination represents a critical advancement in the fight against antimicrobial resistance, offering a new therapeutic option for treating severe infections caused by MDR gram-negative, including MBL-producing, bacteria.
抗菌药物耐药性对公共卫生构成了重大挑战，尤其是随着耐碳青霉烯类革兰氏阴性医院获得性感染的增加。氨曲南-阿维巴坦（ATM-AVI）是一种有前景的新型联合疗法，旨在对抗多重耐药（MDR）革兰氏阴性菌，包括那些产生金属β-内酰胺酶（MBL）的细菌。氨曲南是一种单环β-内酰胺类抗生素，对MBL介导的水解具有抗性，但可被其他β-内酰胺酶降解。阿维巴坦是一种新型非β-内酰胺类β-内酰胺酶抑制剂，可有效中和超广谱β-内酰胺酶（ESBL）和AmpCβ-内酰胺酶，恢复氨曲南对耐药病原体的疗效。本综述涵盖了ATM-AVI的化学结构、作用机制、活性谱、药代动力学、药效学和临床疗效。在体外和临床研究中，ATM-AVI联合疗法已显示出对多种耐药肠杆菌科细菌和其他革兰氏阴性菌有效。药代动力学和药效学分析表明，ATM-AVI在体内维持有效药物浓度，建议对肾功能不全患者进行剂量调整。包括REVISIT和ASSEMBLE研究在内的临床试验已证明ATM-AVI在治疗由MDR革兰氏阴性病原体引起的复杂性腹腔内感染（cIAI）、尿路感染（UTI）和医院获得性肺炎（HAP）方面的安全性和有效性。欧洲药品管理局（EMA）已批准ATM-AVI用于这些适应症，并且正在进行进一步研究以优化给药方案并扩大其临床应用。这种联合疗法是对抗抗菌药物耐药性的一项关键进展，为治疗由MDR革兰氏阴性菌（包括产生MBL的细菌）引起 的严重感染提供了一种新的治疗选择。
