Antimicrobial chemotherapy in patients with cystic fibrosis

Abstract

The treatment of exacerbations of pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis is unsatisfactory. Serum concentrations and urinary excretion of cephalexin, epicillin, azlocillin, ticarcillin, trimethoprim-sulfa and gentamicin useful in the treatment of these infections were investigated in cystic fibrosis patients suffering from pulmonary infections. The data were compared to those found in non-cystic fibrosis children treated with antibiotics for other reasons. Cephalexin and trimethoprim are absorbed at a slower rate; epicillin, azlocillin, ticarcillin sulfonamides were eliminated at a faster rate by the kidneys which was unique to patients with cystic fibrosis. Gentamicin is also eliminated faster. Further investigations disclosed that a considerable amount of drug is eliminated by tubular secretion in addition to the regular glomerular filtration in patients with cystic fibrosis. Creatinine clearance values were determined in these patients and found to be normal. By doubling the dose of gentamicin and administration as infusion over 90 min, higher serum and tissue concentrations were achieved without being in the toxic range. The clinical relevance of these investigations was determined in 36 patients and 48 episodes of infection with P. aeruginosa. Patients received gentamicin 4 mg/kg BW as i.v. infusion over 90 min q. 8 h and azlocillin or ticarcillin 120-160 mg/kg BW q. 8 h, applied 4 h later. In 14 patients respectively 27 episodes, pseudomonas was eradicated from the sputum for a minimum of three weeks, and in most of them for 12-24 weeks. No side effects were observed from the higher doses of aminoglycosides.