The vancomycine is a Antibiotique of the family of the glycopeptides. Bulky (1 500 to 2.000 let us daltons) and complex, it is, as well as the β-lactamines, inhibiting of the synthesis of the peptidoglycane of the bacterial Paroi. But, because of its raised weight, it cannot borrow the porines external membrane of the negative Gram. Its spectrum of action thus touches only the positive Gram.
Vancomycine is Bactéricide, but this bactéricidie is slow to appear; its Biodisponibilité by oral way is negligible, the parenteral way thus is essential generally.
the principal side effects are an attack renal and auditive, it is thus to justify to undertake a regular monitoring of the plasmatic rates of vancomycine.
Enfin, its cost is not negligible and it is often a treatment of last recourse

Indications of the glycopeptides

In curative, they are limited to the following situations:

• severe infections with the germs resistant to the β-lactamines, or when the patient is allergic to these last,
• pseudo-membranous colitis with difficult Clostridium .

Two prophylactic situations are possibly possible:

• Antibioprophylaxie of the bacterial Endocarditis among patients carrying a cardiopathy at the risk, allergic to the β-lactamines and having to undergo a gesture at the risk.
• Antibioprophylaxie of the infections of the operational site in surgeries at the risk staphylococcic (surgery cardiac, vascular, orthopedic, neurosurgery), in circumstances where the risk of infection with Staphylocoque resistant to the méthicilline is increased (begun again surgical early especially) or among patients allergic to the β-lactamines.

Spectrum of action

Vancomycine thus exerts its action only on the positive Gram.

• staphilococca, the such Staphylococcus aureus or staphilococca with coagulase negative, even resistant to the Méticilline. Resistances remain exceptional;
• Streptocoques, whatever they are, including the stocks of sensitivity decreased to the Pénicilline;
• the Entérocoques. One can however meet in human private clinic, of the entérocoques stocks (especially at E faecium the) resistant one to the glycopeptides;
• anaerobic strict with Gram positive: cocci anaerobic, Clostridium ( C perfringens and C difficult ). The vancomycine by oral way is active in the case of the pseudomembraneuses colites with C difficult ;
• Listeria monocytogenes : bacteriostatic activity in vitro, but the diffusion of the vancomycine is random in the liquid céphalorachidien when the Méninges are ignited; in private clinic, these meningitides are thus treated with the Ampicilline, and even if the empirical treatment at the beginning of assumption of responsibility of a meningitis includes already vancomycine IV, one will add ampicilline to it if the circumstances (old or immunosuppressed patient for example) make suspecter Listeria like causal agent.

Pharmacodynamics

As for the β-lactamines, the vancomycine is inhibiting synthesis of the peptidoglycane of the bacterial wall. Its mechanism of action is however different: it is fixed at the level of the ends peptidyl-D-gO-D-Went from the precursors lipopeptidic when they emergent of the cytoplasmic membrane, during their transport through this one, and thus inhibits the stages of transglycosylation and transpeptidation, necessary to the good synthesis of the peptidoglycane, subsequent action of the transpeptidase (which catalyzes the removal of Paved final and the reticulation of the peptidoglycane).
more prosaically, it acts by binding to the components of the wall of the positive bacteria with Gram and by causing the degradation of this one.

Pharmacokinetic

• the oral biodisponibility is negligible. By parenteral way, the intravenous administration of an amount of 1 G makes it possible to obtain, two hours after the injection, of the average serum rates of 25 µg/ml. Around the 11th hour, the concentration is from 3 to 12 µg/ml.
• the connection with plasmatic proteins is from 30 to 60% with the therapeutic concentrations.
• the serum half-life, very variable from one subject to another, is from 4 to 11 a.m.
• the diffusion of the vancomycine is good in the liquids pleural, synovial, péritonéal and pericardial; on the other hand, it is null in the liquid céphalorachidien when the meninges are healthy and random when those are ignited.
• the vancomycine is not metabolized in the organization and its excretion is done to approximately 90% by the kidney in active form (including 75% of 24 hours).

Side effects

• the reactions anaphylactoïdes, induced by a histamino-release comprise pains of the pulsatile type in the muscles of the back and the neck, of the reactions of flush cutaneous of the neck and the shoulders, with a fine transitory eruption, possibly urticarienne: it is the syndrome of “the man-red”. Exceptionally, a hypotension, even a cardiovascular collapse (in particular in the child and the infant) were observed during fast injections. In the majority of the cases, these reactions can be avoided by a slow perfusion (into 60 minimum mn) and a sufficient dilution.
• Nauseas and vomiting is possible undesirable effects.
• local venous toxicity (endoveinite) is consecutive with the administration by peripheral way. It encourages to prefer a center lane.
• the risks of ototoxicity cochléaire and nephrotoxicity (tubulopathy) are increased in a significant way when the plasmatic concentrations of vancomycine are raised or the prolonged treatment. They are it more especially as the patient presents an impaired renal function. Some cases of irreversible renal attack were described. The ototoxicity, especially met during plasmatic concentrations higher than 70-80 mg/l, and the nephrotoxicity are potentiated by the joint administration with other molecules oto- and nephrotoxic, the such Aminoside S.
• the reactions of over-sensitiveness are observed mainly as from the 7th day: generalized cutaneous eruption, hyperéosinophilie, fever.
• Of rare cases of Thrombopénie S (of immuno-allergic cause, i.e., by formation of antibody blood anti-plates) and of Neutropenia S, sometimes severe but quickly reversible to the stop of the treatment, was announced during treatment prolonged.

Resistance

Used since 1956 and in spite of its use as a last resort, the vancomycine is not therefore with the shelter of the development of resistances. There exist thus ERV , entérocoques resistant to the vancomycine , to which the structure D-Go-D-Went from the precursors of the peptidoglycan is replaced by a structure D-Go-D-Lactate not allowing the connection of the vancomycine. Very few treatments of last line are available against these bacteria. One will quote for example the Linézolide. The risk of appearance of such resistances among other groups of bacteria, of which the Staphilococcus S, all the more restricts the use of it.

References

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