Tigecycline tetramesylate
(Synonyms: 替加环素四甲磺酸盐; GAR-936 tetramesylate) 目录号 : GC37789
A glycylcycline antibiotic
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tigecycline is a broad-spectrum glycylcycline antibiotic that binds to the bacterial 30S ribosome, blocking the entry of transfer RNA, which halts protein synthesis and inhibits bacterial growth.1 It is active against a panel of 1,924 European clinical bacterial isolates including S. aureus, S. epidermidis, S. pneumoniae, E. faecalis, E. faecium, E. coli, K. pneumoniae, P. aeruginosa, and P. mirabilis strains (MICs = <1-32 μg/ml).2 In vivo, tigecycline (6.25 mg/kg twice daily for 5 days) decreases levels of C. difficile cytotoxin activity and spore formation in cecum and colon in a mouse model of C. difficile infection.3 Formulations containing tigecycline have been used in the treatment of a variety of bacterial infections.
1.Greer, N.D.Tigecycline (Tygacil): The first in the glycylcycline class of antibioticsProc. (Bayl. Univ. Med. Cent.)19(2)155-161(2006) 2.Milatovic, D., Schmitz, F.J., Verhoef, J., et al.Activities of the glycylcycline tigecycline (GAR-936) against 1,924 recent European clinical bacterial isolatesAntimicrob. Agents Chemother.47(1)400-404(2003) 3.Theriot, C.M., Schumacher, C.A., Bassis, C.M., et al.Effects of tigecycline and vancomycin administration on established Clostridium difficile infectionAntimicrob. Agents Chemother.59(3)1596-1604(2015)
| Cas No. | SDF | ||
| 别名 | 替加环素四甲磺酸盐; GAR-936 tetramesylate | ||
| Canonical SMILES | O=S(C)(O)=O.O=S(C)(O)=O.O=S(C)(O)=O.O=C(C(C1=O)=C(O)[C@@H](N(C)C)[C@]2([H])C[C@]3([H])CC4=C(C(C3=C(O)[C@@]21O)=O)C(O)=C(NC(CNC(C)(C)C)=O)C=C4N(C)C)N.O=S(C)(O)=O | ||
| 分子式 | C33H55N5O20S4 | 分子量 | 970.07 |
| 溶解度 | DMSO: 100 mg/mL (103.09 mM); Water: 50 mg/mL (51.54 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.0309 mL | 5.1543 mL | 10.3085 mL |
| 5 mM | 0.2062 mL | 1.0309 mL | 2.0617 mL |
| 10 mM | 0.1031 mL | 0.5154 mL | 1.0309 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review
Eur J Clin Microbiol Infect Dis 2022 Jul;41(7):1003-1022.PMID:33403565DOI:10.1007/s10096-020-04121-1.
Tigecycline is unique glycylcycline class of semisynthetic antimicrobial agents developed for the treatment of polymicrobial infections caused by multidrug-resistant Gram-positive and Gram-negative pathogens. Tigecycline evades the main tetracycline resistance genetic mechanisms, such as tetracycline-specific efflux pump acquisition and ribosomal protection, via the addition of a glycyclamide moiety to the 9-position of minocycline. The use of the parenteral form of Tigecycline is approved for complicated skin and skin structure infections (excluding diabetes foot infection), complicated intra-abdominal infections, and community-acquired bacterial pneumonia in adults. New evidence also suggests the effectiveness of Tigecycline for the treatment of severe Clostridioides difficile infections. Tigecycline showed in vitro susceptibility to Coxiella spp., Rickettsia spp., and multidrug-resistant Neisseria gonnorrhoeae strains which indicate the possible use of Tigecycline in the treatment of infections caused by these pathogens. Except for intrinsic, or often reported resistance in some Gram-negatives, Tigecycline is effective against a wide range of multidrug-resistant nosocomial pathogens. Herein, we summarize the currently available data on Tigecycline pharmacokinetics and pharmacodynamics, its mechanism of action, the epidemiology of Tigecycline resistance, and its clinical effectiveness.
Emergence of plasmid-mediated high-level Tigecycline resistance genes in animals and humans
Nat Microbiol 2019 Sep;4(9):1450-1456.PMID:31133751DOI:10.1038/s41564-019-0445-2.
Tigecycline is a last-resort antibiotic that is used to treat severe infections caused by extensively drug-resistant bacteria. tet(X) has been shown to encode a flavin-dependent monooxygenase that modifies tigecycline1,2. Here, we report two unique mobile tigecycline-resistance genes, tet(X3) and tet(X4), in numerous Enterobacteriaceae and Acinetobacter that were isolated from animals, meat for consumption and humans. Tet(X3) and Tet(X4) inactivate all tetracyclines, including Tigecycline and the newly FDA-approved eravacycline and omadacycline. Both tet(X3) and tet(X4) increase (by 64-128-fold) the Tigecycline minimal inhibitory concentration values for Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii. In addition, both Tet(X3) (A. baumannii) and Tet(X4) (E. coli) significantly compromise Tigecycline in in vivo infection models. Both tet(X3) and tet(X4) are adjacent to insertion sequence ISVsa3 on their respective conjugative plasmids and confer a mild fitness cost (relative fitness of >0.704). Database mining and retrospective screening analyses confirm that tet(X3) and tet(X4) are globally present in clinical bacteria-even in the same bacteria as blaNDM-1, resulting in resistance to both Tigecycline and carbapenems. Our findings suggest that both the surveillance of tet(X) variants in clinical and animal sectors and the use of tetracyclines in food production require urgent global attention.
Resistance evolution of hypervirulent carbapenem-resistant Klebsiella pneumoniae ST11 during treatment with Tigecycline and polymyxin
Emerg Microbes Infect 2021 Dec;10(1):1129-1136.PMID:34074225DOI:10.1080/22221751.2021.1937327.
Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has recently aroused increasing attention, especially ST11, the predominant CRKP clone in China. Here, we report a case of hv-CRKP-associated infection and reveal the in-host evolution of its mechanism of resistance to Tigecycline and polymyxin under clinical therapy. A total of 11 K. pneumoniae carbapenemase (KPC)-producing CRKP strains were consecutively isolated from a male patient who suffered from continuous and multisite infections. String and antimicrobial susceptibility tests identified seven hypermucoviscous strains and three tigecycline-resistant and four colistin-resistant strains. Galleria mellonella larvae infection model confirmed the hypervirulence. Pulsed-field gel electrophoresis (PFGE) separated three PFGE clusters among all strains, and further Southern blotting detected that blaKPC-2 was located on the same-sized plasmid. Whole-genome sequencing showed that all strains belonged to the hv-CRKP ST11-KL64 clone. Diverse hypervirulence factors and resistance genes were identified. Further sequencing with the Nanopore platform was performed on the CRKP-Urine1 strain, which contained one virulence plasmid (pVi-CRKP-Urine1) and two resistance plasmids (pKPC-CRKP-Urine1 and pqnrS1-CRKP-Urine1). The gene mutations responsible for Tigecycline or colistin resistance were then amplified with PCR followed by sequencing, which indicated that mutations of ramR and lon were the potential loci for Tigecycline resistance and that the pmrB, phoQ and mgrB genes for colistin resistance. A novel frameshift mutation of lon was identified in the high-level tigecycline-resistant strain (MIC, 128 mg/L). The results indicate that the hypervirulent ST11-KL64 clone is a potential threat to antiinfection treatment and is capable of rapid and diverse evolution of resistance during Tigecycline and polymyxin treatment.
Plasmid-encoded tet(X) genes that confer high-level Tigecycline resistance in Escherichia coli
Nat Microbiol 2019 Sep;4(9):1457-1464.PMID:31235960DOI:10.1038/s41564-019-0496-4.
Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria1. Tigecycline resistance has sporadically occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection2,3. Here, we report the emergence of the plasmid-mediated mobile Tigecycline resistance mechanism Tet(X4) in Escherichia coli isolates from China, which is capable of degrading all tetracyclines, including Tigecycline and the US FDA newly approved eravacycline. The tet(X4)-harbouring IncQ1 plasmid is highly transferable, and can be successfully mobilized and stabilized in recipient clinical and laboratory strains of Enterobacteriaceae bacteria. It is noteworthy that tet(X4)-positive E. coli strains, including isolates co-harbouring mcr-1, have been widely detected in pigs, chickens, soil and dust samples in China. In vivo murine models demonstrated that the presence of Tet(X4) led to Tigecycline treatment failure. Consequently, the emergence of plasmid-mediated Tet(X4) challenges the clinical efficacy of the entire family of tetracycline antibiotics. Importantly, our study raises concern that the plasmid-mediated Tigecycline resistance may further spread into various ecological niches and into clinical high-risk pathogens. Collective efforts are in urgent need to preserve the potency of these essential antibiotics.
Tigecycline-induced coagulopathy: a literature review
Int J Clin Pharm 2019 Dec;41(6):1408-1413.PMID:31713108DOI:10.1007/s11096-019-00912-5.
Background Several adverse reactions to Tigecycline, which is widely used in patients with severe infections, have been documented. Coagulopathy is a lesser known side effect of Tigecycline. Aim of the review We summarize the characteristics, possible mechanisms, and treatment of tigecycline-induced coagulopathy. Method PubMed, Ovid, Embase, ISI Web of Knowledge, CNKI, and Wanfang were searched up to March 5, 2019. All articles concerning coagulopathy induced by Tigecycline were included. The article types and languages were not limited. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts. Results Ultimately, 17 articles were targeted, including 13 case reports and 4 retrospective observational studies. Tigecycline-induced coagulopathy usually manifests as the dose-dependent prolongation of prothrombin time and activated partial thromboplastin time and a reduction in the fibrinogen level. Tigecycline and its metabolites may have multiple effects on coagulation, influencing the extrinsic or intrinsic pathway and even the common pathway. There is no specific treatment for tigecycline-induced coagulopathy, but it can be reversed by withdrawing Tigecycline. Conclusion Tigecycline acts on the coagulation system in a dose-dependent manner, and the most severe adverse event is bleeding. Overdose and prolonged use should be avoided, suspected coagulopathy must be recognized in time, and Tigecycline should be withdrawn to prevent severe adverse events. Also, drug clearance disorders can develop in patients with liver and/or renal dysfunction. For patients with severe hepatic or renal impairment, the maintenance dose should be reduced, and indicators of coagulation function should be closely monitored.