JMI Laboratories, North Liberty, Iowa, USA
JMI Laboratories, North Liberty, Iowa, USA.
Antimicrob Agents Chemother. 2020 Apr 21;64(5). doi: 10.1128/AAC.02375-19.
KBP-7072 is a novel third-generation tetracycline (aminomethylcycline) antibacterial that overcomes common efflux and ribosomal protection resistance mechanisms that cause resistance in older-generation tetracyclines. KBP-7072 completed phase 1 clinical development studies for safety, tolerability, and pharmacokinetics (ClinicalTrials.gov identifier NCT02454361) and multiple ascending doses in healthy subjects (ClinicalTrials.gov identifier NCT02654626) in December 2015. Both oral and intravenous formulations of KBP-7072 are being developed. In this study, we evaluated the activities of KBP-7072 and comparator agents by CLSI document M07 (2018) broth microdilution against 531 recent geographically diverse and/or molecularly characterized - species complex () isolates from the United States, Europe, Asia-Pacific (excluding China), and Latin America. isolates included carbapenem-resistant, colistin-resistant, tetracycline-resistant, and extended-spectrum-β-lactamase (ESBL)- and metallo-β-lactamase (MBL)-producing isolates. Overall, KBP-7072 (MIC, 0.25/1 mg/liter) was comparable in activity to colistin (92.8%/92.8% susceptible [S] [CLSI/EUCAST]) against isolates, inhibiting 99.2% of isolates at ≤2 mg/liter and 97.6% of isolates at ≤1 mg/liter. KBP-7072 was equally active against isolates, including carbapenem-resistant, colistin-resistant, and tetracycline-resistant isolates, regardless of geographic location, and maintained activity against ESBL- and MBL-producing isolates. KBP-7072 outperformed comparator agents, including ceftazidime (40.3% S [CLSI]), gentamicin (48.2%/48.2% S [CLSI/EUCAST]), levofloxacin (39.5%/37.9% S [CLSI/EUCAST]), meropenem (42.0%/42.0% S [CLSI/EUCAST]), piperacillin-tazobactam (33.3% S [CLSI]), and all tetracycline-class comparator agents, which include doxycycline (67.3% S [CLSI]), minocycline (73.8% S [CLSI]), tetracycline (37.2% S [CLSI]), and tigecycline (79.5% inhibited by ≤2 mg/liter). The potent activity of KBP-7072 against recent geographically diverse, molecularly characterized, and drug-resistant isolates supports continued clinical development for the treatment of serious infections, including those caused by .
KBP-7072 是一种新型第三代四环素（氨甲基环素）抗菌药物，克服了常见的外排和核糖体保护耐药机制，这些机制导致了老一代四环素的耐药性。KBP-7072 已于 2015 年 12 月完成了安全性、耐受性和药代动力学（ClinicalTrials.gov 标识符 NCT02454361）以及健康受试者的多剂量递增（ClinicalTrials.gov 标识符 NCT02654626）的 I 期临床开发研究。KBP-7072 的口服和静脉制剂均在开发中。在这项研究中，我们按照 CLSI 文件 M07（2018）肉汤微量稀释法评估了 KBP-7072 和对照剂对 531 株来自美国、欧洲、亚太地区（不包括中国）和拉丁美洲的近期地理多样化和/或分子特征明确的 种复合体（）分离株的活性。 分离株包括耐碳青霉烯类、多粘菌素耐药、四环素耐药以及产超广谱β-内酰胺酶（ESBL）和金属β-内酰胺酶（MBL）的分离株。总体而言，KBP-7072（MIC，0.25/1mg/L）对 分离株的活性与多粘菌素（92.8%/92.8%敏感[S] [CLSI/EUCAST]）相当，对≤2mg/L 的 99.2%分离株和≤1mg/L 的 97.6%分离株有抑制作用。KBP-7072 对 分离株同样有效，包括耐碳青霉烯类、多粘菌素耐药和四环素耐药的分离株，无论地理位置如何，并对产 ESBL 和 MBL 的分离株保持活性。KBP-7072 优于对照剂，包括头孢他啶（40.3% S [CLSI]）、庆大霉素（48.2%/48.2% S [CLSI/EUCAST]）、左氧氟沙星（39.5%/37.9% S [CLSI/EUCAST]）、美罗培南（42.0%/42.0% S [CLSI/EUCAST]）、哌拉西林-他唑巴坦（33.3% S [CLSI]）和所有四环素类对照剂，包括多西环素（67.3% S [CLSI]）、米诺环素（73.8% S [CLSI]）、四环素（37.2% S [CLSI]）和替加环素（≤2mg/L 抑制率为 79.5%）。KBP-7072 对近期地理多样化、分子特征明确和耐药的 分离株具有强大的抗菌活性，支持其继续开发用于治疗严重感染，包括由 引起的感染。
