Structural Biochemistry/Vancomycin

Molecular structure of vancomycin including stereochemistry.

Background

Vancomycin is considered a last-resort antibiotic, and tends to be effective in treating bacteria that is highly resistant to many, if not all, other drugs. It is a glycopeptide, derived from Amycolatopsis orientalis cultures. One of the most well-known bacteria that vancomycin is effective against is methicillin-resistant Staphylococcus aureus (MRSA). Overall, vancomycin is successful against various Gram-positive bacteria, including highly resistant streptococci, enterococci, and staphylococci strains. Vancomycin should not be taken as an oral medication, as it cannot be absorbed that way, but rather through an intravenous injection. ^[1]

Overview

Vancomycin works by binding with the terminal amino acids of peptidoglycan chains in cell walls. By doing so, the production of the bacterial cell wall is prevented by not allowing the cross-linking between neighboring peptidoglycan strands. Without a strong wall, cell lysis is induced and the bacterial cell falls apart. ^[1]

Mechanism of Vancomycin

In bacterial cells the cell wall consists of peptidoglycan. This peptidoglycan is made up of repeating units of two sugar molecules, N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). Attached to NAM is a series of amino acids that end with a D-alanine dipeptide. Inside the cytoplasm at the cell membrane, NAM and NAG are linked at the bactoprenol to form the disaccharide NAM-NAG. NAM-NAG is brought to the outside area of the cell membrane by the bactoprenol, where penicillin binding proteins (PBPs) bind to the D-Ala dipeptide. One PBP is transpeptidase, which links the peptide side chains of two NAG molecules to form a peptide cross link. This peptide cross link helps to add stability to the cell wall by connecting a L-lysine of one NAM side chain to the D-Ala of another NAM side chain. ^[2]

Vancomycin binds to the D-Ala-D-Ala end of the NAM-NAG disaccharide and prevents transpeptidase from making the peptide cross link. ^[2] As autolysins continue breaking the peptide cross link and no new cross link can be formed because of Vancomycin, the bacterium bursts as a result of osmotic lysis.

Medicinal Uses

Vancomycin hydrochloride is primarily used in the treatment of severe infections resulting from susceptible strains of methicillin-resistant staphylococci. Typically, vancomycin is a last resort type of antibiotic that is normally used for patients allergic to penicillin, for those that haven't responded to other types of antibiotics (like cephalosporins), and for patients plagued by vancomycin-susceptible bacteria. Courses of treatment should be determined once the type of bacteria is identified and susceptibility data has been obtained. It has been effective against staphylococcal endocarditis, other infections from staphylococci (bone infections, respiratory infections, and skin infections). Other types of infections that vancomycin has been effective against include diphtheroid endocarditis. To improve the effectiveness of combating bacterial infections, vancomycin will often be used with aminoglycosides or rifampin. Vancomycin is not effective against viral infections.

Like all medications, there are typically risks and side effects associated with each drug. As with most antibiotics, the risk of developing drug-resistant bacteria has become an ever increasing battle. When drug-resistant bacteria form, it becomes more difficult to treat and combat the infections related from these bacteria. Vancomycin must be administered intravenously because the drug is very irritating to the tissue. If the medication interacts with the muscle tissue, typically there is associated muscle pain, tenderness, and the tissue begins to die, therefore supporting the need to administer vancomycin intravenously. Also, prolonged use of vancomycin with other medications can have adverse effects as well. For example, prolonged use with anesthetics can lead to complications such as hypotension, pruritis, and erythema. Some of the side effects with antibiotics typically include diarrhea and stomach pains. Other effects include anaphylaxis, drug fever, nausea, chills, and rashes.

Source: http://www.drugs.com/pro/vancomycin-hydrochloride.html

Side Effects

Vancomycin can trigger violent allergic reactions on certain individuals. The most common severe symptoms are:

hives
swelling on the lips, face, throat or tongue
hearing loss
fever
lightheadedness
extreme stomach pain
fainting

Incompatibility with other drugs

When mixed with certain other drugs, vancomycin can cause severe reactions. The most common drugs that react with vancomycin are:

amikacin
gentamicin
kanamycin
neomycin
streptomycin
tobramycin

Reference: http://www.drugs.com/vancomycin.html http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000282/ http://pharmacologycorner.com/vancomycin-mechanism-action-animation/

References

↑ ^a ^b ^c Dewick, Paul M. Medicinal Natural Products: A Biosynthetic Approach, Third Edition, John Wiley and Sons Ltd. 2009.
↑ ^a ^b Slonczewski, Joan L. Foster, John W. Microbiology: An Evolving Science, Second Edition, W.W. Norton & Company. 2009.

[Dewick-1] Dewick, Paul M. Medicinal Natural Products: A Biosynthetic Approach, Third Edition, John Wiley and Sons Ltd. 2009.

[Slonczewski-2] Slonczewski, Joan L. Foster, John W. Microbiology: An Evolving Science, Second Edition, W.W. Norton & Company. 2009.

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