Glycylcyclines

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Tigecycline, a drug approved in the United States

Glycylcyclines are a class of antibiotics that are derived from tetracyclines . Glycylcyclines were developed to overcome typical mechanisms of antibiotic resistance to tetracyclines. This applies to bacterial efflux pumps on the one hand, but also to ribosomal starting points. Tigecycline is currently the only approved representative of this group of active ingredients.

history

In the 1980s and 1990s, there was increasing evidence of tetracycline resistance in various bacterial strains. In the early 1990s, the modification of the glycylcyclines was developed by adding an N , N -dimethylglycylamido side chain to tetracyclines . Efflux pumps and ribosomal protective mechanisms of the bacteria were thereby circumvented. Tigecycline is the first clinically approved substance.

Mechanism of action

Glycylcycline antibiotics act like tetracyclines by blocking protein synthesis . The bacteriostatic effect results from binding to the 30S subunit of the bacterial ribosomes , which prevents amino-acyl-tRNA from binding to ribosomes. Glycylglycines show an even stronger binding potential than tetracyclines.

Resistance Mechanisms

Glycylcyclines are not eliminated by acquired efflux pumps, but chromosomal efflux pumps as in Pseudomonas and Proteus are resistance-inducing. Ribosomal resistance to tetracyclines is overcome by glycylcyclines.

Side effects and contraindications

Glycylcyclines also resemble their precursor active ingredients, the tetracyclines, in terms of the spectrum of side effects: nausea and vomiting, headaches, sensitivity to light, tooth discoloration, fetal malformations.

Avoid use in pregnant women. Due to the potential for permanent tooth discolouration, it should not be used in children during tooth development either. Hypersensitivity reactions are possible, including cross-reactivity with tetracyclines.

Individual evidence

  1. ^ Drugs @ FDA: FDA Approved Drug Products - Tigecycline . United States Food and Drug Administration. Retrieved March 15, 2019.
  2. ↑ Bergeron J, Ammirati M, Danley D, etal: Glycylcyclines bind to the high-affinity tetracycline ribosomal binding site and evade Tet (M) - and Tet (O) -mediated ribosomal protection . In: Antimicrob. Agents Chemother. . 40, No. 9, September 1996, pp. 2226-2228. PMID 8878615 . PMC 163507 (free full text).
  3. ↑ Livermore DM: Tigecycline: what is it, and where should it be used? . In: J. Antimicrob. Chemother. . 56, No. 4, October 2005, pp. 611-614. doi : 10.1093 / jac / dki291 . PMID 16120626 .
  4. ^ List of adverse events for Tigecycline . RxList.com. Retrieved December 18, 2016.