Continuous infusion of ceftazidime in cystic fibrosis patients during home treatment: Clinical outcome, microbiology and pharmacokinetics

Acute exacerbations of Pseudomonas aeruginosa lung infections were treated with ceftazidime by continuous infusion in 17 adult patients with cystic fibrosis at home. Ceftazidime was delivered via an infusion pump and the effects of this 3 week home intravenous antibiotic treatment (HIVAT) were prospectively studied over a 2 year period. Patients with cystic fibrosis (eight male and nine female patients; mean age 26.9 +/- 7.6 years, range 15-52 years), received a total of 33 courses of continuous ceftazidime (100 mg/kg/24 h). Clinical data were collected at the start, the end and 4-6 weeks after the end of treatment in 12 patients. Ceftazidime pharmacokinetic data during continuous infusion were obtained from ten patients. The treatment was supervised by the clinician without home visits. All 25 clinically evaluable courses in 12 patients proved efficacious. The mean duration of the courses was 21 days. The entire antibiotic course was administered at home in 88% of the courses. The other 12% was started for 2-3 days as an inpatient. Objective clinical parameters significantly improved. Clinical improvement was noted in 91% of the patients, and lasted at least until 4-6 weeks after the end of the treatment in 70%. The number of cultures positive for P. aeruginosa decreased significantly during antibiotic treatment. Bacterial count returned to pretreatment values 4-6 weeks after treatment. Multiple courses of ceftazidime monotherapy did not result in a lasting increase of ceftazidime-resistant pseudomonas strains. Total body clearance was 9.1 +/- 1.3 L/h. The steady-state ceftazidime serum concentration during continuous infusion was 28.4 +/- 5.0 mg/L. Sputum concentrations were in the range of 0.5-13 mg/L (3.9 +/- 4.0 mg/L). In conclusion, HIVAT with ceftazidime administered by continuous infusion proved clinically effective and did not result in an increase in lasting resistance.