Pharmacology of Glycopeptides

Glycopeptides are used in the treatment of Gram-positive bacterial infections. They remain an important class in the treatment of serious infections where other medicines have proven insufficient or ineffective.

Examples of glycopeptides include:

  • Vancomycin
  • Teicoplanin
  • Telavancin

Glycopeptides are used in the treatment of the following infections:

  • Complicated skin infections
  • Bloodstream infections
  • Endocarditis
  • Bone and joint infections
  • Meningitis caused by MRSA

Teicoplanin is not available in the US.

Telavancin is most commonly used for severe skin infections and MRSA infections.

All glycopeptides are used in the treatment of Gram-positive infections only. As we learn more about their mechanism of action, it becomes clear to see why.

Mechanism of action

Glycopeptides are cell wall synthesis inhibitors in Gram-positive bacteria – both aerobic and anaerobic organisms.

Glycopeptides are ineffective against almost all Gram-negative organisms because of differences in the lipopolysaccharide cell wall. It means that glycopeptides are unable to penetrate the cell wall and cause the structural disturbances it otherwise causes in Gram-positive organisms.

Gram-positive organisms have a backbone to their call wall – namely, intertwining strands of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG). Glycopeptides bind to the D-Ala-D-Ala formation that prevents synthesis of these polymers.

This compromises the structural integrity of the cell wall and destroys the bacteria.

Side effects

Side effects associated with glycopeptide antibacterials include:

  • Thrombophlebitis at the injection site
  • “Red man syndrome” – a reaction that often results from rapid infusion, leading to side effects such as upper body flushing and rash
  • Hypotension
  • Bone marrow suppression

Immediate or delayed hypersensitivity reactions can occur.

Though glycopeptides are often associated with ototoxicity and nephrotoxicity, it is widely believed that these effects were more common in earlier investigations but are, on review, much rarer than first believed. Nonetheless, they do remain risks.

Clinical considerations

When we talk about the clinical pharmacology of glycopeptides, we need to think about the following factors:

  • That dose reductions are required in vulnerable populations – such as the elderly, or in those with established renal damage.
  • That many drugs – such as aminoglycosides, loop diuretics and ciclosporin – increase the risk of both nephrotoxicity and ototoxicity.
  • That glycopeptides, like vancomycin, cannot be absorbed via the GI tract. Instead, they must be administered via parenteral routes, such as the IV route. However, oral vancomycin is available to treat pseudomembranous colitis.

Glycopeptides are important medicines in the treatment of Gram-positive infections, particularly infections that have proven resistant to more established therapies. It’s worth recognising that their resistance does, though, continue to increase.

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