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Vancomycin
Teicoplanin
Mode of action
- bind to the D-ALA-D-ALA terminal end of peptidoglycan precursors. (Peptidoglycans
are the basic building blocks of bacterial cell walls).
- this inhibits the action of transglycosidase and transpeptidases (required
for cross-linking of peptidoglycans - basic building block of cell wall)
- inhibit RNA synthesis
Resistance
- due to substitution of D-lactic acid instead of terminal D-ALA. Prevents
binding of glycopeptide.
Pharmacodynamics
- very slow killing
- time-dependent
killing
- moderate post-antibiotic effect (approximately 2 h)
- synergistic effect in vitro with aminoglycosides: facilitates
penetration of latter into bacterial cells.
Spectrum of activity
Gram positive organisms only
Usually sensitive organisms:
Usually resistant organisms:
- Leuconostoc spp.
- Lactobacillus spp.
- Pediococcus spp.
- Erysipelothrix spp.
Glycopeptide resistant organisms
- vancomycin and teicoplanin resistant enterococci. Several different types
of resistance:
- VanA
- high-level
resistance (MIC at least
64 mg/L)
- r
- t
- r
- results
in substitution of lactate for D-Ala in terminal D-Ala-D-Ala of
peptide chain in peptidoglycans and interference with glycopeptide
binding
- VanB
- low
level resistance (MIC 8-32 mg/L)
- only inducible by vancomycin and thus does not result in
teicoplanin resistance
- also results in substitution of lactate for D-Ala
- VanC
- constitutive form of resistance seen in Enterococcus gallinarum
- low level resistance
- VanD
- constitutive resistance found in one strain of Enterococcus
faecium
- high level resistance to vancomycin and low level resistance to
teicoplanin
Pharmacokinetics
Administration
Intravenous. Although can be given orally for Clostridium
difficile related diarrhoea. (Note the IV preparation can be given
enterally instead of the more expensive enteral preparation). Significant
amounts may be absorbed from the GI tract in patients with colitis
Distribution
- most body tissues and fluids but unless meninges are inflammed there is
little diffusion into CSF
- 55% bound to plasma protein
Elimination
- mainly by glomerular filtration. 80% of a dose excreted within 24h in
urine
- small amount excreted in faeces
- limited elimination by haemofiltration
Dosage
Reduce dose in renal failure and severe hepatic failure
Concentration monitoring
Aim for peak concentration approximately 30mg/l (20-40) and trough
concentration <10 mg/l
Adverse effects
- histamine release due to too rapid an infusion. Results in anaphylactoid
reaction, muscular spasms, and sometimes hypotension ("red man
syndrome")
- nephrotoxicity especially in combination with other renal insults
- very occasional ototoxicity
Pharmacokinetics
-
admin:
IV/IM. Absorption after IM injection equivalent to that after IV injection
-
distribution:
poor CSF penetration. Volume of distribution 0.8-1.6 l/kg
-
elimination:
almost entirely renal. t1/2 155-168 hrs. Clearance values
correlate with creatinine clearance. Not removed from circulation by
haemodialysis
Clinical uses
-
treatment of gram positive
infections
-
empirical therapy in
immunocompromised patients with haematological malignancies requiring
intensive chemotherapy. Associated with a lower incidence of Candida
superinfection
-
as effective as vancomycin in
treatment of Clostridium difficile associated diarrhoea and colitis
Adverse effects
-
one
or more in approx 10% of patients
-
incidence
of renal impairment (especially in combination with an aminoglycoside) lower
than that associated with vancomycin
-
lesser
propensity to cause anaphylactic-type reactions (“red man syndrome”)
-
allergic
type reactions in 2.6%
-
altered
LFTs in 1.7%
-
altered
renal function tests in 0.6%
-
pyrexia
0.8%
-
ototoxicity
0.3%
Dosage
Adults with normal renal function:
loading dose of 400 mg (approx 6 mg/kg) followed by 200-400 mg od. Increase
maintenance dose to 12 mg/kg for patients with septic arthritis and for
empirical treatment of patients with fever and neutropaenia give 3 12 hrly
loading doses of 6-12 mg/kg followed by normal maintenance doses
Adults with acute or chronic renal
impairment: Give usual adult dose for first few days then modify dose to
maintain a trough serum level of <10 mg/l. Serum concentration monitoring
also necessary in patients with a history of IV drug abuse to ensure adequate
therapeutic levels.
Children < 12 years: 3 doses of 10
mg/kg 12 hrly followed by 6-10 mg/kg daily
Further reading
Brogden
RN, Peters DH. Teicoplanin. A reappraisal of its antimicrobial activity,
pharmacokinetic properties and therapeutic efficacy. Drugs, 1994; 47:823-54 Rahman
H, Smith L. Glycopeptides. In Armstrong D, Cohen J.
Infectious diseases. Mosby, London, 1999, pp7/10.1-7/10.6
Van Bambeke F. Mechanisms of action. In Armstrong D, Cohen J.
Infectious diseases. Mosby, London, 1999, pp7/1.1-7/1.14
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