Vancomycin

Vancomycin
	Structural formula
Mass / length primary structure	7 amino acids (partially modified), 1450 Daltons
Identifier
External IDs	CAS number : 1404-90-6;
Drug information
ATC code	A07 AA09 J01 XA01;
DrugBank	DB00512
Drug class	Glycopeptide antibiotic

Vancomycin is an antibiotic from the group of glycopeptide antibiotics . It was isolated from cultures of Amycolatopsis orientalis ( Streptomyces orientalis ) in 1955 and used as an effective alternative against multi-resistant staphylococci from 1980 . In addition to enterococci, staphylococci are often found in hospitals as the cause of nosocomial infections . Vancomycin is a third-line antibiotic that is used when other drugs are no longer effective due to resistance . It is not absorbed by the intestine, which can be used in antibiotic-associated colitis .

Mechanism of action

Vancomycin inhibits the build-up of the bacterial cell wall by forming a complex with the terminal L- lysine - D- alanyl- D -alanine groups of the bacterial cell wall component murein . It blocks the building blocks of the cross-linking of the cell wall of gram-positive bacteria through a bridge of five glycine residues (pentaglycine bridge / pentapeptide side chain ), so that certain building blocks important for the cross-linking ( N -acetylglucosamine, N -acetylmuramic acid) are no longer built into the growing bacterial cell wall. Vancomycin's mechanism of action as a glycopeptide is not based on binding to transglycosylase. Since bacteria have a relatively high osmotic pressure , the cell wall cannot withstand this pressure without the crosslinking, and the bacterium bursts.

synthesis

Glycosyltransferases GtfB glycosylate the precursor to the effective vancomycin in tandem action .

use

Systemic treatment

Vancomycin is given as an intravenous infusion or injection to treat severe infections caused by gram-positive pathogens that are resistant to other antibiotics (e.g. oxacillin-resistant Staphylococcus aureus ). Vancomycin has long been the last hope for treating life-threatening infections caused by gram-positive spherical bacteria ( cocci ), as a reserve antibiotic . That hope ended in 1987 when vancomycin-resistant enterococci (VRE) emerged in hospitals.

Linezolid has been considered a reserve antibiotic ( last line of defense ) for several years .

Vancomycin is also used in perioperative antibiotic prophylaxis , e.g. B. when implanting a port catheter with simultaneous neutropenia.

In the case of simultaneous therapy with aminoglycosides, in patients with unstable kidney function, patients requiring dialysis or in the case of high doses and longer therapy periods, as well as in severe infections, the serum levels (peak level: 30–40 mg / L; trough level: 10–15 mg / L) of vancomycin increase check.

Topical treatment

Vancomycin works very well in antibiotic-associated pseudomembranous enterocolitis caused by Clostridioides difficile . The antibiotic, which cannot be absorbed in the intestine , is administered orally. In the case of pseudomembranous enterocolitis, however, the much cheaper metronidazole is primarily used, with which there are fewer problems with the development of resistance (vancomycin-resistant enterococci, VRE).

Formation of resistance

Avoparcin

Vancomycin resistance is in part due to the expression of an alternative D -alanyl: D -alanine ligase . This alternative enzyme ligates D -lactate instead of D -alanine, resulting in a (-OH) - instead of a (-NH ₂ ) terminus. This prevents the binding of vancomycin and enables the crosslinking of the murein via a depsipeptide bond . Another type of resistance formation is the expression of a D -Ala: D -Ser ligase instead of the D -Ala: D -Ala ligase.

The growth accelerator avoparcin , which is structurally similar to vancomycin, is considered to be the trigger for the spread of vancomycin-resistant enterococci . It was used in animal fattening in Germany until 1996. Since 1997 avoparcin may no longer be used as a feed additive in the European Union.

Finished medicinal products

Vancomycin was developed by Eli Lilly and launched on the market in 1955, initially in the USA. Only the water-soluble vancomycin hydrochloride is used medicinally , either as a powder for the preparation of an infusion solution (for systemic therapy ) and as a powder for the preparation of an oral solution or as a capsule (for topical therapy ).

Vancomycinhaltige medicine is available under the brand name Vancocin ( "Lilly" ) and under the generic name ( generic name ) in the market (eg. As vancomycin CP Lilly ).

literature

Constanze Wendt, Henning Rüden, Michael Edmond: Vancomycin-Resistant Enterococci: Epidemiology, Risk Factors and Prevention. In: Deutsches Ärzteblatt . (Cologne) 95 (25), 1998, pp. A1604-A1611.
Dudley H. Williams, Ben Bardsley: The Vancomycin Antibiotics and the Fight Against Resistant Bacteria. In: Angewandte Chemie . 111 (9), 1999, pp. 1264-1286.
G. Schulze, W. Schott, G. Hildebrandt: Vancomycin-Resistant Enterococci - Hospital Kitchen as a Vector? In: Federal Health Gazette . 44 (7), 2001, pp. 732-737.
F. Dieber, G. Gorkiewicz, J. Kofer: Detection of vancomycin-resistant enterococci in animal production in Styria. In: Working conference of the field of food hygiene. 44, 2003, pp. 449-454.
Brian K. Hubbard, Christopher T. Walsh: The Structure of Vancomycin: How Nature Does It. In: Angewandte Chemie. 115 (7), 2003, pp. 752-789.
Hermann Feldmeier: Antibiotic resistance due to unnatural feeding. In: Naturwissenschaftliche Rundschau . 57 (11), pp. 632-633.
A. Simon, N. Gröger, S. Engelhart, G. Molitor, M. Exner, U. Bode, G. Fleischhack: Vancomycin-Resistant Enterococci (VRE) - Overview of Importance, Prevention and Management in Pediatrics. In: Hygiene and Medicine. 29 (7/8), 2004, p. 259 ff.
W. Witte, I. Klare, G. Werner: Selective pressure by antibiotics as feed additives. In: Infection. 27 (Suppl 2), 1999, pp. 35-38.

Individual evidence

↑ Karl Wurm, AM Walter: Infectious Diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 9–223, here: p. 53.
↑ Igor Pochorovski: Synthesis of Vancomycinsonden for activity-based protein profiling in the Google Book Search
↑ K. Aktories, U. Förstermann, F. Hofmann, K. Starke: General and special pharmacology and toxicology. 10th edition. Elsevier, Munich 2009, ISBN 978-3-437-42522-6 .
^ William Barry Hugo, SP Denyer, Norman A. Hodges, SP Gorman: Hugo and Russell's pharmaceutical microbiology . John Wiley & Sons, 2004, ISBN 978-0-632-06467-0 ( limited preview in Google Book Search).
↑ Heather C. Losey, Mark W. Peczuh, Zhong Chen, Ulrike S. Eggert, Steven D. Dong, Istvan Pelczer, Daniel Kahne, Christopher T. Walsh: Tandem action of glycosyltransferases in the maturation of vancomycin and teicoplanin aglycones: novel glycopeptides . In: Biochemistry. Volume 40, No. 15, 2001, pp. 4745-4755, doi: 10.1021 / bi010050w .
^ Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich, 2nd, revised and expanded edition. Peter Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , pp. 335-337.
↑ BfR: avoparcin ban initiated in Germany by BgVV (accessed on 20 February 2011).
^ AE van den Bogaard, N. Bruinsma and EE Stobberingh: The effect of banning avoparcin on VRE carriage in The Netherlands . In: Journal of Antimicrobial Chemotherapy . tape 46 , no. 1 . The British Society for Antimicrobial Chemotherapy, 2000, pp. 146-148 , doi : 10.1093 / jac / 46.1.146 ( oxfordjournals.org [accessed February 20, 2011]).

[1] Karl Wurm, AM Walter: Infectious Diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 9–223, here: p. 53.

[2] Igor Pochorovski: Synthesis of Vancomycinsonden for activity-based protein profiling in the Google Book Search

[aktories10-3] K. Aktories, U. Förstermann, F. Hofmann, K. Starke: General and special pharmacology and toxicology. 10th edition. Elsevier, Munich 2009, ISBN 978-3-437-42522-6 .

[4] William Barry Hugo, SP Denyer, Norman A. Hodges, SP Gorman: Hugo and Russell's pharmaceutical microbiology . John Wiley & Sons, 2004, ISBN 978-0-632-06467-0 ( limited preview in Google Book Search).

[5] Heather C. Losey, Mark W. Peczuh, Zhong Chen, Ulrike S. Eggert, Steven D. Dong, Istvan Pelczer, Daniel Kahne, Christopher T. Walsh: Tandem action of glycosyltransferases in the maturation of vancomycin and teicoplanin aglycones: novel glycopeptides . In: Biochemistry. Volume 40, No. 15, 2001, pp. 4745-4755, doi: 10.1021 / bi010050w .

[6] Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich, 2nd, revised and expanded edition. Peter Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , pp. 335-337.

[bfr-7] BfR: avoparcin ban initiated in Germany by BgVV (accessed on 20 February 2011).

[oxfordjournals-8] AE van den Bogaard, N. Bruinsma and EE Stobberingh: The effect of banning avoparcin on VRE carriage in The Netherlands . In: Journal of Antimicrobial Chemotherapy . tape 46 , no. 1 . The British Society for Antimicrobial Chemotherapy, 2000, pp. 146-148 , doi : 10.1093 / jac / 46.1.146 ( oxfordjournals.org [accessed February 20, 2011]).