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.