L'antibiothérapie dans la mucoviscidose. I. Particularités pharmacologiques des antibiotiques

Abstract

Antibiotherapy is one of the main treatment in cystic fibrosis. Antibiotic administration schedules are different from normal patients because of pharmacokinetic and pharmacodynamic particularities. In moderate disease, the digestive resorption of antibiotics is delayed and their half-life is reduced due to an increase in total clearance. In severe disease, the volume of distribution of antibiotics is increased due to the higher proportion of lean mass in these malnourished patients. Other particularities limit the action of antibiotics such as thick sputum, which limits drug penetration; the property of Pseudomonas aeruginosa to be surrounded by a biofilm; alteration of local antibacterial defense; and inhibition of antibiotics by local factors. Systematic prescription of a biotherapy beta-lactam-aminoglycoside and obtaining high antibiotic concentration in situ might limit this antagonism. In spite of particular therapeutic schedules such as single daily dose for aminoglycoside and continuous infusion for beta-lactams, the intervals between administrations must be narrowed for time-dependent antibiotics, and the total daily dose increased by 20 to 30% for concentration-dependent antibiotics.