Glycopeptides

crop_square Key points

  • check_circle Bactericidal antibiotics primarily used against multi-drug resistant organisms
  • check_circle Inhibit bacterial cell wall synthesis by binding to peptidoglycan precursors
  • check_circle Only active against gram-positives, including MRSA
  • check_circle Increasing resistance to vancomycin is a major concern

crop_square Background and biochemistry

Glycopeptide antibiotics have been in clinical use for more than 60 years. Most drugs in this class are primarily used as a last resort against multi-drug resistant organisms. Natural glycopeptides (vancomycin, teicoplanin) were isolated from bacteria (vancomycin: Amycolatopsis orientalis). The core structure of glycopeptide antibiotics consists of cyclic peptide rings with attached amino sugars. The semisynthetic newer lipoglycopeptides Telavancin, Dalbavancin and Oritavancin were developed to counter increasing resistance to natural glycopeptides, mainly in staphylococcal and enterococcal strains. Daptomycin was isolated from Streptomyces roseosporus and is a lipopeptide antibiotic.

crop_square Mechanism of action

Glycopeptides inhibit bacterial cell wall synthesis by binding to precursors of peptidoglycans. This leads to increased permeability of the cell wall and ultimately to cell lysis and bacterial cell death. Resistances to glycopeptides take generally longer to develop compared to other antibiotics due to their complex mechanism of action. However, vancomycin and teicoplanin resistance, especially in enterococci and staphylococci, are on the rise and a major concern. Daptomycin disrupts bacterial cell wall integrity by causing rapid membrane depolarisation and potassium influx leading to cell death. Daptomycin resistance is only sporadically reported until now. Glycopeptides and lipopeptides are bactericidal.

crop_square Drugs and spectrum of activity

  • Vanco­mycin
  • Teico­planin
  • Dapto­mycin
  • Dalba­vancin
  • Orita­vancin
  • Tela­vancin

Glycopeptides, lipopeptides and glycolipopeptides are active against gram-positive bacteria only. They are commonly used to treat infections with suspected drug-resistant organisms and should be used with caution to prevent the emergence of new resistant strains. Vancomycin is given in staphylococcal sepsis and bacterial endocarditis. As an oral antibiotic, vancomycin is used to treat complicated cases of Clostridium difficile infections. Daptomycin serves as a last-line antibiotic with a spectrum of activity similar to glycopeptides. Laboratory studies showed good activity against vancomyin/glycopeptide resistant enterococci (VRE/GRE) but clinical data are scarce. Strains resistant to vancomycin (VISA/VRE) or all glycopeptides (GISA/GRE) may be susceptible to semisynthetic glycolipopeptides.

crop_square Pharmacokinetics

Vancomycin is poorly absorbed orally. Glycopeptides and daptomycin are primarily cleared by the kidneys. The half-lives of most these antibiotics require one or two doses given over 24h. Vancomycin shows inflammation-dependent good tissue and CNS penetration. In the absence of inflammation, the blood-brain barrier is insufficiently crossed.

crop_square Adverse drug effects

Vancomycin is poorly absorbed orally. Glycopeptides and daptomycin are primarily cleared by the kidneys. The half-lives of most these antibiotics require one or two doses given over 24h. Vancomycin shows inflammation-dependent good tissue and CNS penetration. In the absence of inflammation, the blood-brain barrier is insufficiently crossed.