Glycopeptides

Glycopeptides are bactericidally active systemic (glycopeptides are not absorbed by oral application) antibiotics with complex polycyclic structures. They are counted among the so-called reserve antibiotics. Glycopeptides have good tissue mobility, but are only slightly absorbed by the cerebrospinal fluid.

glycopeptides:

• Dalbavancin
• Vancomycin
• Teicoplanin
• Telvancin

Elimination takes place mainly renally in an unchanged form, to a small extent also biliary.

Half-lives of glycopeptides

• Vancomycin 4-6 h
• Telvancin 8 h
• Teicoplanin 150 h
• Dalbavancin 372 h

Glycopeptides disturb the regular structure of the bacterial cell wall by binding with high affinity to the oligopeptides that are responsible for the stabilizing cross-linking of the bacteria's murein scaffold. By binding to the terminal D-alanyl-D-alanine of the UDP-muramyl peptide, they prevent the elongation of the peptidoglycan chains and their cross-linking and thus the formation of the cell membrane. Telvancin also disrupts cell function by depolarising the bacterial cell membrane.

Glycopeptide antibiotics are effective against aerobic and anaerobic gram-positive germs. They are ineffective against Gram-negative germs because their molecular size prevents them from penetrating the outer cell wall of Gram-negative bacteria.

Of particular importance is the use of glycopeptides against Staphylococcus, Enterococci and Clostridium difficile if lower-risk antibiotics cannot be given. Their use is important in severe systemic infections with staphylococci, pneumococci, enterococci (osteomyelitis, pneumonia, meningitis, endocarditis). In MRSA infections and penicillin-resistant pneumococci, glycopeptides are combined with rifampicin, in enterococcal endocarditis with gentamicin.

Vancomycin is also used for the oral treatment of pseudomembranous colitis, which is caused by an overgrowth of Clostridium difficile after prior administration of another antibiotic. In this case the effect is only in the intestine (Note: a better alternative is metronidazole to prevent selection of vancomycin-resistant enterococci).

Telvancin has so far only been approved for the therapy of nosocomial pneumonia caused by MRSA.

Dalbavancin: Dalbavancin, a semi-synthetic lipophilic glycopeptide, has been available since 2016 and is used in acute bacterial skin and soft tissue infections(ABSSI). It is only supplied to hospitals.

Note: Due to the increasing development of resistance, the risk of therapy failure should not be underestimated.

Development of resistance: Changes in the target structures lead to a high degree of resistance of enterococci, especially E. faecium, to vancomycin. Instead of D-alanine, D-lactate is replaced in the preliminary stage of murein in a modified biosynthesis. D-lactate lacks a hydrogen atom, which is present in D-alanine. Therefore it cannot form a hydrogen bond with the glycopeptide antibiotic. The binding capacity of vancomycin decreases. In staphylococci there is an overproduction of murein precursors. The murein synthesis itself is not affected.

ENT-UAW

• Ototoxicity (dose-dependent; >1000mg vancomycin, >500mg teicoplanin), it requires careful monitoring of patients, especially in the case of long-term use or reduced renal function

Nephrological UAW

• Renal damage (dose-dependent)

Immunological ADRs:

• Allergic skin reactions (Red man's syndrome - occurs during rapid infusion of vancomycin as a result of massive histamine release)
• Inflammatory reactions at the injection site

Hematological UAW

• Reversible neutropenia under vancomycin (dose-dependent)

Nephrological UAW

Risk factor is renal insufficiency and the combination with other nephrotoxic and potentially ototoxic drugs, such as loop diuretics, ciclosporin and cisplatin, increases the risk of hearing and balance disorders. Vancomycin increases and prolongs the effect of muscle relaxants.

Teicoplanin: Pregnancy and lactation

Acute renal failure

Hearing loss

1. Graefe KH et al. Antibacterial agents. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S.581-583

2. Huang V et al (2020) Glycopeptides Hypersensitivity and Adverse Reactions. Pharmacy (Basel). 8:70.