Morgan Gina M, Critchley Ian, Cotroneo Nicole, Sader Helio, Castanheira Mariana, Mendes Rodrigo
JMI Laboratories/Element Materials Technology, North Liberty, Iowa, USA.
Spero Therapeutics, Cambridge, Massachusetts, USA.
Microbiol Spectr. 2025 Sep 10:e0134125. doi: 10.1128/spectrum.01341-25.
Increasing rates of antimicrobial resistance require additional safe and effective options for managing difficult-to-treat infections. SPR206 is a next-generation polymyxin with improved safety profiles. This study determined the activity of SPR206 against a diverse collection of gram-negative isolates. SPR206 was tested against 5,179 Enterobacterales, , and spp. collected from patients in the United States (US), Europe, Israel, and Turkey. Broth microdilution was performed following the Clinical & Laboratory Standards Institute (CLSI) guidelines, and MIC results interpreted by CLSI, European Committee on Antimicrobial Susceptibility Testing (EUCAST), and United States Food and Drug Administration (US FDA) criteria. SPR206 (MIC, 0.25/0.25-0.5 mg/L) was active against , including the multidrug-resistant, extensively drug-resistant, and difficult-to-treat subsets, with 99.8-100% of isolates inhibited at MIC values of ≤2 mg/L. SPR206 inhibited 94.5% of spp., including 90.4 and 87.9% of the multidrug-resistant (MIC, 0.12/2 mg/L) and extensively drug-resistant (MIC, 0.12/8 mg/L) subsets at MIC values of ≤2 mg/L. SPR206 (MIC, 0.06/0.25 mg/L) inhibited 95.4% of non-Morganellaceae Enterobacterales at MIC values of ≤2 mg/L. SPR206 MIC and MIC values of 0.06 and 0.5 mg/L were obtained against carbapenem-resistant Enterobacterales from the US and Western Europe, whereas MIC of 0.5 mg/L and MIC of 64 mg/L were noted against carbapenem-resistant Enterobacterales isolates from Eastern Europe. SPR206 demonstrated potent activity against a large collection of gram-negative organisms, including resistant subsets. These results, along with an enhanced safety profile, warrant the development of SPR206 as a candidate for the treatment of infections caused by gram-negative bacteria.IMPORTANCESPR206 is a novel, next-generation polymyxin with improved safety profiles that demonstrates activity against gram-negative organisms. This study benchmarks the activity and spectrum of SPR206 against a large collection of gram-negative isolates, including multidrug-resistant and extensively drug-resistant spp. and , and carbapenem-resistant Enterobacterales collected from multiple medical sites in the US and Europe. Additional treatment options are needed as antimicrobial resistance emerges and spreads. The results presented in this manuscript show potent SPR206 activity against resistant and difficult-to-treat gram-negative organisms.
日益增加的抗菌药物耐药率需要有更多安全有效的选择来治疗难治性感染。SPR206是一种安全性更高的新一代多粘菌素。本研究确定了SPR206对多种革兰氏阴性菌分离株的活性。对从美国、欧洲、以色列和土耳其患者中收集的5179株肠杆菌科细菌、假单胞菌属和不动杆菌属细菌进行了SPR206测试。按照临床和实验室标准协会（CLSI）指南进行肉汤微量稀释，并根据CLSI、欧洲抗菌药物敏感性试验委员会（EUCAST）和美国食品药品监督管理局（US FDA）的标准解释MIC结果。SPR206（MIC，0.25/0.25 - 0.5 mg/L）对肠杆菌科细菌有活性，包括多重耐药、广泛耐药和难治性亚组，99.8 - 100%的分离株在MIC值≤2 mg/L时被抑制。SPR206抑制了94.5%的假单胞菌属细菌，包括多重耐药（MIC，0.12/2 mg/L）和广泛耐药（MIC，0.12/8 mg/L）亚组中90.4%和87.9%的细菌，在MIC值≤2 mg/L时。SPR206（MIC，0.06/0.25 mg/L）在MIC值≤2 mg/L时抑制了95.4%的非摩根菌属肠杆菌科细菌。从美国和西欧的耐碳青霉烯类肠杆菌科细菌中获得的SPR206的MIC和MIC值分别为0.06和0.5 mg/L，而从东欧的耐碳青霉烯类肠杆菌科细菌分离株中观察到的MIC为0.5 mg/L，MIC为64 mg/L。SPR206对大量革兰氏阴性菌，包括耐药亚组，表现出强大的活性。这些结果，连同其更高的安全性，保证了将SPR206开发为治疗革兰氏阴性菌引起的感染的候选药物。重要性SPR206是一种新型的、安全性更高的新一代多粘菌素，对革兰氏阴性菌有活性。本研究对SPR206针对大量革兰氏阴性菌分离株的活性和谱进行了基准测试，这些分离株包括多重耐药和广泛耐药的假单胞菌属和不动杆菌属细菌，以及从美国和欧洲多个医疗地点收集的耐碳青霉烯类肠杆菌科细菌。随着抗菌药物耐药性的出现和传播，需要更多的治疗选择。本手稿中呈现的结果显示了SPR206对耐药和难治性革兰氏阴性菌的强大活性。
