Vancomycin is a glycopeptide antibiotic produced by bacteria. It works by binding to D-Ala-D-Ala sites on bacterial cell walls, inhibiting cell wall synthesis. It is administered intravenously and excreted renally. Vancomycin is used to treat serious infections caused by gram-positive bacteria like MRSA and is generally well-tolerated though it can cause histamine-related flushing. Other glycopeptide antibiotics discussed include teicoplanin, telavancin, and dalbavancin, which have similar mechanisms of action to vancomycin but varying pharmacokinetic properties and clinical applications.

1. University of Kufa
College of Medicine
Department of pharmacology & therapeutics
Done by :-
Qassim A. Zigum

2. OUTLINE
 INTRODUCTION
 HISTORY
 VANCOMYCIN
◊◊ Mechanisms of Action
◊◊ Mechanisms of Resistance
◊◊ Antibacterial Activity
◊◊ Pharmacokinetics
◊◊ Clinical Uses
◊◊ Adverse Reactions
 OTHER GLYCOPEPTIDES 2

3. INTRODUCTION
 Glycopeptide are non-beta lactam cell wall
synthesis inhibitors antibiotics .
 are composed of glycosylated cyclic or
polycyclic nonribosomal peptides.
 include the :-
◊◊ anti – infective antibiotics ( vancomycin ,
teicoplanin, and telavancin)
◊◊ anti – tumor antibiotic ( bleomycin )
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4. HISTORY
 Vancomycin was isolated in 1953, and used
clinically from 1955. Approved in 1958 by FDA to
treat penicillin resistant staphylococci. MRSA first
seen in 1961.
 Bleomycin was first discovered in 1966.
 Teicoplanin was discovered in the early 1990s.
 Telavancin is a semi-
synthetic lipoglycopeptide derivative of vancomycin
(approved by FDA in 2009).
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5. VANCOMYCIN
 Vancomycin is an antibiotic produced by
Streptococcus orientalis and Amycolatopsis
orientalis.
 With the exception of Flavobacterium , it is active
only aginst gram-positive bacteria.
 Vancomycin is a glycopeptide of molecular weight
1500 dalton . It is water soluble and quite stable.
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6. MECHANISMS OF ACTION
 Vancomycin inhibits cell wall synthesis by binding
firmly to the D-Ala-D-Ala terminus of nascent
peptidoglycan pentapeptide .
 This inhibits the transglycosylase, preventing
further elongation of peptidoglycan and cross-
linking.
 The peptidoglycan is thus weakened, and the cell
becomes susceptible to lysis.
 The cell membrane is also damaged, which
contributes to the antibacterial effect.
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7. MECHANISMS OF ACTION
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8. BASES OF RESISTANCE
 Changing the D-Ala-D-Ala unite of the
peptidoglycane to D-Ala-D-Lactate which cannot be
bond to vancomycin.
 This results in the loss of a critical hydrogen bond
that facilitates high affinity binding of vancomycin to
its target and loss of activity.
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9. BASES OF RESISTANCE
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R
O
N
H
O
H CH3
O
O
O
H CH3
R
O
N
H
H
N
H CH3
O
O
H CH3
O
C-Terminus of D-Ala-D-Ala peptide
C-Terminus of D-Ala-D-Lactate peptide

10. ANTIBACTERIAL ACTIVITY
 Vancomycin is bactericidal for gram-positive bacteria in
concentrations of 0.5–10 mcg/mL.
 Most pathogenic staphylococci, including those
producing β lactamase and those resistant to nafcillin
and methicillin, are killed by 2 mcg/mL or less.
 Vancomycin kills staphylococci relatively slowly and
only if cells are actively dividing; the rate is less than
that of the penicillins both in vitro and in vivo.
 Vancomycin is synergistic in vitro with gentamicin and
streptomycin against Enterococcus faecium and
Enterococcus faecalis strains that do not exhibit high
levels of aminoglycoside resistance.
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11. ANTIBACTERIAL SPECTRUM
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12. PHARMACOKINETICS
 Vancomycin is poorly absorbed from the
intestinal tract and is administered orally only for
the treatment of antibiotic-associated colitis caused
by C. difficile .
 Parenteral doses must be administered
intravenously. A 1-hour intravenous infusion of 1 g
produces blood levels of 15–30 mcg/mL for 1–2
hours.
 The drug is widely distributed in the body.
Cerebrospinal fluid levels 7–30% of simultaneous
serum concentrations are achieved if there is
meningeal inflammation. 12

13. PHARMACOKINETICS
 Ninety percent of the drug is excreted by glomerular
filtration.
 The drug has a serum elimination half-life of about
6 hours.
 In the presence of renal insufficiency, striking
accumulation may occur .
 In functionally a nephric patients, the half-life of
vancomycin is 6–10 days.
 A significant amount (roughly 50%) of vancomycin
is removed during a standard hemodialysis run
when a modern, high-flux membrane is used.
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14. PHARMACOKINETICS
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15. CLINICAL USES
 Blood stream infections and endocarditis caused by
methicillin-resistant staphylococci MRSA.
 enterococcal endocarditis in a patient with serious
penicillin allergy( in combination with gentamicin) .
 meningitis suspected or known to be caused by a
penicillin-resistant strain of pneumococcus(in
combination with cefotaxime, ceftriaxone, or
rifampin)
 Oral vancomycin, 0.125–0.25 g every 6 hours, is
used to treat antibiotic
associated pseudomembranous colitis caused by
C. difficile .
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16. ADVERSE REACTIONS
 Adverse reactions are encountered in about 10% of
cases (Most reactions are minor).
 Vancomycin is irritating to tissue, resulting in
phlebitis at the site of injection.
 Chills and fever may occur.
 Ototoxicity is rare and nephrotoxicity uncommon
with current preparations.
 “red man” or “red neck” syndrome.
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18. OTOTOXICITY AND NEPHROTOXICITY
 Ototoxicity is rare and nephrotoxicity
uncommon with current preparations.
 However, administration with
another ototoxic or nephrotoxic drug,
such as an aminoglycoside, increases
the risk of these toxicities.
 Ototoxicity can be minimized by maintaining
peak serum concentrations below 60 mcg/mL.
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19. “RED MAN” OR “RED NECK” SYNDROME.
 This infusion-related flushing is
caused by release of histamine.
 It can be largely prevented by
prolonging the infusion period
to 1–2 hours or pretreatment
with an antihistamine such as
diphenhydramine.
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20. TEICOPLANIN
 Teicoplanin is a glycopeptide antibiotic that is very
similar to vancomycin in mechanism of action and
antibacterial spectrum.
 Unlike vancomycin, it can be given intra- muscularly
as well as intravenously.
 Teicoplanin has a long half-life (45–70 hours),
permitting once-daily dosing .
 This drug is available in Europe but has not been
approved for use in the United States.
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21. TELAVANCIN
 Telavancin is a semisynthetic lipoglycopeptide
derived from vancomycin.
 The half-life of telavancin is approximately 8 hours,
which supports once-daily intravenous dosing.
 Telavancin is approved for treatment of complicated
skin and soft tissue infections at a dose of 10 mg/kg
IV daily.
 Telavancin is potentially teratogenic, so
administration to pregnant women must be avoided.
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22. DALBAVANCIN
 Dalbavancin is a semisynthetic lipoglycopeptide
derived from teicoplanin.
 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 onceweekly intravenous
administration.
 Development of dalbavancin has been put on hold
pending additional clinical trials.
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23. DALBAVANCINTELAVANCINTEICOPLANINVANCOMYCINPARAME
TERS
IVIVIV,IMIV,PORout of
adm.
6-11days8hr45-70hr6-8hrHalf life
Category CCategory C
Teratogenic
Category CCategory CPregnancy
lipoglycopeptide ,
derived from
teicoplanin
Lipoglycopepti
de ,derived
from
vancomycin
GlycopeptideGlycopeptideNature
Approved by FDA
in May 2014
approved by
FDA in 2009
early 1990sApproved in
1958
History
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