Vancomycin and Other Glycopeptides

  • Glycopeptide antibiotics are actinomycete-derived antibiotics with unique tricyclic or tetracyclic heptapeptide cores that are usually glycosylated.
  • bactericidal
  • inhibits cell wall synthesis by inhibiting transglycosylase enzyme (involved in chain elongation).
  • It has narrow spectrum
  • effective against gram positive organisms including MRSA, penicillin resistant pneumococci and Clostridium difficile.
  • drug of choice for MRSA, Corynebacterium jeikeium and for serious infections in penicillin allergic patients.
  • Glycopeptides – most prevalent class of therapeutics against  severe infections caused by :
  • Gram-positive pathogens:
  • 1) Enterococci
  • 2) Methicillin-resistant staphylococcus aureus (MRSA)
  • 3) Clostridium difficile
  • MRSA – Endemic in India à Hospital acquired infection
  • A study showed overall prevalence of methicillin resistance  as 41 %. Isolation rates for MRSA from OPD, IPD and ICU were 27, 49 and 47 per cent in 2009.
  • Classification of glycopeptide antibiotics

Mechanism of action

  • The bacterial cell wall- peptidoglycan– structural support.
  • Peptidoglycan monomers- sugar backbone with peptide and disaccharide units attached by glycosidic bonds into long chains via Transglycosidation.
  • The glycopeptide antibiotics- cell membrane- noncovalent bonds with terminal carbohydrates- inhibition of cross-linking by the Transpeptidase.
  • Subsequently, the weakened cell wall- cell cytolysis and death.


  • Primary target: D-Ala-D-Ala terminus of pentapeptidic precursors
  • Vancomycin forms complex with the D-Ala-D-Ala residues by forming five hydrogen bonds with the peptide backbone of the glycopeptide.
  • This complex prevents the transpeptidation reactions via steric hindrance.
  • These are administered parenterally (vancomycin by i.v. route and teicoplanin by i.v. or i.m. route) and are excreted unchanged in urine.

Clinical uses

  • Blood stream infections and endocarditis caused by MRSA.
  • Enterococcal endocarditis in a patient with serious penicillin allergy (with gentamicin) .
  • Meningitis suspected or known to be caused by a penicillin-resistant strain of pneumococcus (with cefotaxime, ceftriaxone, or rifampin)
  • Other infections due to staphylococci – septicemias, LRTI, bone, skin and skin structure infections
  •  Oral vancomycin, 0.125–0.25 g every 6 hours – antibiotic associated  pseudomembranous colitis by C. Difficile – because it is not absorbed from the gastrointestinal tract and higher concentration reaches the colon.

Adverse reactions

  • Adverse reactions in about 10% of cases (most reactions are minor).
  • “Red man” or “red neck” syndrome à Rapid i.v. infusion of high doses of vancomycin can cause RED MAN SYNDROME (diffuse flushing due to histamine release). It is the most common adverse

reaction to vancomycin.

  • Phlebitis at the site of injection.
  • Chills and fever
  • Ototoxicity( rare)and nephrotoxicity uncommon with current  preparations.
  • Its dose should be decreased in renal failure.

Mechanism of resistance

  • Enterococci- mediated by acquirement of a gene à codes for enzymes: synthesis of low- affinity and removal of high- affinity peptidoglycan precursors                                      
  • Nine types of vancomycin resistance (Van A to Van N)
  • Van A enterococci- resistance induced by Vancomycin and Teicoplanin
  • Van B enterococci – sensitive to Vancomycin, resistant to Teicoplanin.


  • Teicoplanin is another glycopeptide with similar characteristics but can be given once daily due to long t1/2 (45-70 hours).
  • The fatty-acid component increased lipophilicityà greater cellular and tissue penetration
  • Mechanism
  • It inhibits the synthesis of peptidoglycans in the bacterial cell wall by the nonspecific binding
  • 2) The saturation of the outer layers of bacterial peptidoglycans.
  • 3) Teicoplanin then binds to the D-Ala-D-Ala terminus of the   precursors, which fits into a cleft in the teicoplanin molecule
  • Teicoplanin does not cause red man syndrome or nephrotoxicity.
  • Indicated for treatment of serious infections by staphylococcus or streptococcus

      1) Bone- osteomyelitis

      2) joints- septic arthritis

      3) blood- non cardiac bacteremia, septicemia

  • Unlike vancomycin, it can be given IM and IV
  • Teicoplanin has a long half-life (45–70 hours), permitting once-daily dosing .

Semisynthetic glycopeptides

Telavancin, Oritavancin and Dalbavancin


 1) Overcome the emergence of MRSA strains showing weaken sensitivity to Vancomycin

 2) To increase the penetration into tissues and into CSF

 3) Longer half-life in comparison with Vancomycin

 4) Improvements for infrequent dosing

 5) Greater potency

 6) Lower risk of development of resistant microorganisms.


  • FDA approval in 2009
  • A derivative of vancomycin:
    •  Lipophilic group: increased membrane interactions
  • Phosphonate group: improved adsorption, distribution, metabolism and the excretion profile of telavancin.
  • Dual mechanism of action– Inhibition of peptidoglycan biosynthesis and membrane depolarization.
  • Apart from vancomycin like mechanism, it also disrupts membrane potential.
  • approved à treatment of complicated skin and soft tissue infections à 10 mg/kg IV daily.
  • Clinical use subsequently extended to include hospital-acquired and ventilator-associated bacterial pneumonia
  • potentially teratogenic, so administration to pregnant women must be avoided
  • The half-life of telavancin is approximately 8 hours, which supports once-daily intravenous dosing.


  • Approved in May 2014.
  • A semisynthetic derivative of the teicoplanin-like glycopeptide A40926 complex, derived from Nonomuraea sp.
  • Three phase-III trials successfully completed between 2003 and 2005, but the FDA required additional non-inferiority data in 2007
  • In 2009, two additional phase-III trials were initiated which met their primary endpoint of non-inferiority.
  • Amidation of the C-terminal carboxyl group with a dimethylaminopropylamine group produced dalbavancin
  • These modifications led to an extended half-life of over 300 h in human allowing for once weekly dosing.


  • Approved for the treatment of adult patients with complicated skin and skin structure infections, including those caused by MRSA
  • It is not active against most strains of vancomycin-resistant enterococci.
  • Dalbavancin has an extremely long half-life of 6–11 days, which allows for once weekly intravenous administration


  • Approved in August 2014
  • Two phase-III trials completed with results disclosed in 2001 and 2003, but the FDA rejected a new drug application (NDA) in 2008 for concerns over safety and effectiveness.
  • In 2009, 2 more phase-III trials for Gram-positive ABSSSI completed. 


  • The injection form is approved for treatment of acute bacterial skin and skin structure infections (ABSSSI)
  •  Dimer formation- residual activity against vancomycin-resistant bacteria.
  •  Intrinsic bactericidal activity especially against streptococci
  •  Effectiveness – not affected by the antibiotic-resistance mechanisms developed by staphylococci and enterococci, effective in VRSA and VRE

Spectrum of activity

  • Aerobic gram-positive microorganisms
    • Listeria monocytogenes
    •  Streptococcus pyogenes
    • Streptococcus pneumoniae (including penicillin-resistant strains)
    • Streptococcus agalactiae
  • Anaerobic gram-positive microorganisms
    • Actinomyces species
    •  Lactobacillus species

Drugs under trial

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.