Laboratory of Clinical Microbiology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Front Cell Infect Microbiol. 2022 Jan 20;11:814530. doi: 10.3389/fcimb.2021.814530. eCollection 2021.
is a leading cause of healthcare-associated infections worldwide, due to both its persistence in the hospital setting and ability to acquire high levels of antibiotic resistance. Carbapenem-resistant isolates (CRAB) limit the activity of current antimicrobial regimens and new alternatives or adjuncts to traditional antibiotics are urgently needed. Durlobactam is a novel broad-spectrum inhibitor of serine-type β-lactamases that restores sulbactam (SUL) activity against . The sulbactam-durlobactam (SD) combination has recently completed Phase 3 testing in the global ATTACK trial.
The aim of this study is to evaluate the activity of SD versus comparators against a representative nationwide collection of CRAB isolates.
One hundred ninety CRAB isolates were collected from clinical samples of patients hospitalized in 11 hospitals throughout Greece during 2015. activities of SD and comparators (SUL alone, amikacin, minocycline, imipenem, meropenem, colistin, SD and imipenem combined with SD) were determined by broth microdilution.
Durlobactam restored sulbactam activity against the majority of the strains tested, with SD exhibiting the lowest MIC (8 μg/ml) relative to the other single comparators tested; 87.9% of the isolates had SD MICs ≤4/4 µg/ml. The most active comparator was colistin (MIC = 16 μg/ml). The addition of imipenem further lowered the MIC of SD by one two-fold dilution.
This study demonstrated the potential utility of SD for the treatment of infections caused by . If its clinical efficacy is confirmed, SD may be an important therapeutic option for CRAB infections.
碳青霉烯类耐药肠杆菌科细菌(Carbapenem-Resistant Enterobacteriaceae,CRE)是全球导致医疗保健相关感染的主要原因,这归因于其在医院环境中的持久性和获得高水平抗生素耐药性的能力。耐碳青霉烯类肠杆菌科细菌(Carbapenem-Resistant Enterobacteriaceae,CRE)限制了当前抗菌方案的活性,迫切需要新的替代物或抗生素辅助物。多黏菌素类酶抑制剂 Durlobactam 是一种新型广谱丝氨酸型β-内酰胺酶抑制剂,可恢复舒巴坦(Sulbactam,SUL)对肠杆菌科细菌的活性。舒巴坦-多黏菌素类酶抑制剂(Sulbactam-Durlobactam,SD)组合最近在全球 ATTACK 试验中完成了 3 期测试。
本研究旨在评估 SD 对代表性全国 CRE 分离株的活性与对照药物的比较。
从 2015 年希腊 11 家医院住院患者的临床样本中收集了 190 株 CRE 分离株。通过肉汤微量稀释法测定 SD 和对照药物(单独舒巴坦、阿米卡星、米诺环素、亚胺培南、美罗培南、黏菌素、SD 和 SD 联合亚胺培南)对 SD 的活性。
多黏菌素类酶抑制剂 Durlobactam 恢复了舒巴坦对大多数测试菌株的活性,SD 的最低 MIC(8μg/ml)相对于其他测试的单药对照物;87.9%的分离株的 SD MICs≤4/4μg/ml。最有效的对照药物是黏菌素(MIC=16μg/ml)。亚胺培南的加入使 SD 的 MIC 进一步降低了一个二倍稀释度。
本研究表明 SD 治疗由 CRE 引起的感染具有潜在的应用价值。如果其临床疗效得到证实,SD 可能成为治疗 CRE 感染的重要治疗选择。