Tigecycline, the first commercially available member of the glycylcyclines, is a new class of antimicrobial agents.
The glycylcyclines are the derivatives of tetracycline antibiotics, with modifications in the structure showing potent activity against gram-positive, gram-negative, and certain multidrug-resistant strains [1]. Tigecyclineis bacteriostatic could reversibly bind to the 30S ribosomal subunit thus inhibiting protein translation [1].
In vitro:Tigecycline exihibited good in vitro activities. The range of MIC90s was 0.12-0.5 μg/ml for vancomycin-susceptible and -resistant strains of Enterococcus faecalis and Enterococcus faecium [2]. Tigecyclinewas concentrated in cells and eliminated primarily via biliary excretion. Diminished renal function didn’t significantly alter its systemic clearance. Tigecycline didn’t interfere with common cytochrome P450 enzymes, making pharmacokinetic drug interactions uncommon [3].The tissue penetration of tigecycline was excellent and the compound showed equivalence to imipenem/cilastatin in intra-abdominal infection and to vancomycin plus aztreonam in skin and skin structure infection [4].
In vivo: In an intraperitoneal systemic murine infection model, tigecycline exihibited in vivo activities against GISA, methicillin-susceptible S. aureus and methicillin-resistant S. aureus strains [2]. Tigecycline and daptomycin showed similar in vivo efficacies against infections caused by the MSSA strain (strain GC 4543) with the ED50s of 0.12 and 0.24 mg/kg, respectively. The ED50s of tigecycline was 0.72 mg/kg [2].
Clinical trials: For complicated skin and skin-structure infections in hospitalized patients receiving tigecycline (50-mg, q12h), the microbial eradication rates and clinical cure rates were 70% and 74%. In patients who received 25-mg doses, the results were 56% and 67% [5]. Adverse events including increased nausea and vomiting appeared in treating patients with cSSSI. Tigecycline monotherapy was as safe and efficacious as the vancomycin-aztreonam combination in treating patients with cSSSI[6].
参考文献:
[1] Rose W E, Rybak M J.? Tigecycline: first of a new class of antimicrobial agents[J]. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2006, 26(8): 1099-1110.
[2] Petersen P J, Bradford P A, Weiss W J, et al.? In vitro and in vivo activities of tigecycline (GAR-936), daptomycin, and comparative antimicrobial agents against glycopeptide-intermediate Staphylococcus aureus and other resistant gram-positive pathogens[J]. Antimicrobial agents and chemotherapy, 2002, 46(8): 2595-2601.
[3] Stein G E, Craig W A.? Tigecycline: a critical analysis[J]. Clinical infectious diseases, 2006, 43(4): 518-524.
[4] Livermore D M.? Tigecycline: what is it, and where should it be used[J]. Journal of Antimicrobial Chemotherapy, 2005, 56(4): 611-614.
[5] Postier R G, Green S L, Klein S R, et al.? Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients[J]. Clinical therapeutics, 2004, 26(5): 704-714.
[6] Grosse E J E, Babinchak T, Dartois N, et al.? The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam[J]. Clinical infectious diseases, 2005, 41(Supplement 5): S341-S353.
| Antimicrobial susceptibility testing [1]: | |
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Bacteria |
Resistant and susceptible gram-positive strains |
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Preparation method |
The solubility of this compound in DMSO is > 29.3 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
18 ~ 22 hrs |
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Applications |
Tigecycline exhibited similar in vitro activities against the GISA, Methicillin-resistant and Methicillin-susceptible staphylococcal strains (MIC90 = 0.5 ~ 1 μg/mL). Besides, Tigecycline also demonstrated good in vitro activities for Vancomycin-susceptible and -resistant strains of Enterococcus faecalis and Enterococcus faecium, with MIC90 ranging from 0.12 ~ 0.5 μg/mL. |
| Animal experiment [1]: | |
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Animal models |
An intraperitoneal systemic murine infection model |
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Dosage form |
0.2 mL, 0.01 M; i.v; a single dose |
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Applications |
For infection caused by a MSSA strain, Daptomycin and Tigecycline showed similar in vivo efficacy with the ED50 values of 0.12 and 0.24 mg/kg, respectively. Besides, Tigecycline and Daptomycin also exhibited similar in vivo efficacy against infection caused by a MRSA strain, with the ED50 values of 0.72 and 0.87 mg/kg, respectively. However, Tigecycline was most effective against an infection caused by a GISA strain, with an ED50 values of 1.9 mg/kg, 3 times more efficacious than Daptomycin (ED50 = 6.1 mg/kg). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Petersen P J, Bradford P A, Weiss W J, et al. In vitro and in vivo activities of tigecycline (GAR-936), daptomycin, and comparative antimicrobial agents against glycopeptide-intermediate Staphylococcus aureus and other resistant gram-positive pathogens[J]. Antimicrobial agents and chemotherapy, 2002, 46(8): 2595-2601. | |
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