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新型氟环素 TP-6076 对耐碳青霉烯鲍曼不动杆菌的体外活性。

In vitro activity of the novel fluorocycline TP-6076 against carbapenem-resistant Acinetobacter baumannii.

机构信息

Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany; German Center for Infection Research (DZIF), partner site Bonn-Cologne, Germany.

Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.

出版信息

Int J Antimicrob Agents. 2020 Jan;55(1):105829. doi: 10.1016/j.ijantimicag.2019.10.010. Epub 2019 Dec 16.

Abstract

The activity of the novel, fully synthetic fluorocycline antibiotic TP-6076 against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates with defined carbapenem resistance mechanisms was compared against reference antimicrobials with known activity against Acinetobacter spp. The susceptibility of 323 non-duplicate CRAB isolates to TP-6076, amikacin, ampicillin/sulbactam (SAM), cefepime, colistin, doxycycline, eravacycline, imipenem, levofloxacin, meropenem, minocycline, rifampicin, sulbactam, tigecycline, tobramycin and trimethoprim/sulfamethoxazole (SXT) was determined by the broth microdilution method. TP-6076 showed greater activity than comparator antimicrobials of the tetracycline class, SAM, levofloxacin, amikacin, tobramycin, SXT and colistin. MIC and MIC values for TP-6076 were 0.06 mg/L and 0.25 mg/L, respectively. In comparison, doxycycline, eravacycline, minocycline and tigecycline MIC values were 32/≥64, 0.5/1, 4/8 and 1/2 mg/L, respectively. Compared with other compounds, TP-6076 was the most active antimicrobial against CRAB, including isolates that were resistant to other anti-Acinetobacter reference drugs including SAM, colistin, the aminoglycosides amikacin and tobramycin, and levofloxacin. TP-6076 is a promising new agent that may be a useful addition to the limited armamentarium of drugs targeting this problematic pathogen.

摘要

新型全合成氟环素抗生素 TP-6076 对具有明确碳青霉烯类耐药机制的耐碳青霉烯鲍曼不动杆菌(CRAB)分离株的活性与具有已知抗不动杆菌活性的参考抗菌药物进行了比较。采用肉汤微量稀释法测定 323 株非重复 CRAB 分离株对 TP-6076、阿米卡星、氨苄西林/舒巴坦(SAM)、头孢吡肟、多粘菌素、强力霉素、依拉环素、亚胺培南、左氧氟沙星、美罗培南、米诺环素、利福平、舒巴坦、替加环素、妥布霉素和复方磺胺甲噁唑(SXT)的敏感性。TP-6076 对四环素类、SAM、左氧氟沙星、阿米卡星、妥布霉素、SXT 和多粘菌素的活性均优于比较药物。TP-6076 的 MIC 和 MIC 值分别为 0.06 mg/L 和 0.25 mg/L。相比之下,强力霉素、依拉环素、米诺环素和替加环素的 MIC 值分别为 32/≥64、0.5/1、4/8 和 1/2 mg/L。与其他化合物相比,TP-6076 是对 CRAB 最具活性的抗菌药物,包括对 SAM、多粘菌素、氨基糖苷类阿米卡星和妥布霉素以及左氧氟沙星等其他抗不动杆菌参考药物耐药的分离株。TP-6076 是一种很有前途的新型药物,可能是针对这种有问题的病原体的有限药物武器库中的一个有用的补充。

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