Ciprofloxacin has potent in vitro activity against Pseudomonas aeruginosa and Pseudomonas cepacia strains isolated from
cystic fibrosis patients. Our previous single-dose pharmacokinetic and pharmacodynamic studies identified important differences between
cystic fibrosis patients and age- and sex-matched controls. Based on these data, 30 acutely ill
cystic fibrosis patients (aged 18 to 44 years) received 750 mg of
ciprofloxacin orally every eight hours for 21 days. Multiple timed serum, urine, and sputum samples for pharmacokinetic analysis were obtained on Days 3, 12, 14, and 21 of the study. Estimates of steady-state pharmacokinetic parameters averaged (+/- SD): t1/2 beta, 3.8 (1) hours; Vd/F, 4.4 (2) liters/kg; Cl/F, 772.9 (301) ml/minute/1.73 m2; Fe, 46 percent; peak, 5.4 (2) mg/liter; and trough, 1.8 (0.8) mg/liter. Serum
ciprofloxacin concentrations and pharmacokinetic estimates remained unchanged throughout the study. Sputum
ciprofloxacin concentrations exceeded those observed in serum. Sputum cultures revealed 43 P. aeruginosa (MIC90 = 2 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml) strains. Sputum
ciprofloxacin concentrations exceeded the MIC90 for P. aeruginosa approximately fivefold, yet only eight isolates were fully suppressed. Posttreatment sputum cultures revealed 35 P. aeruginosa (MIC90 = 16 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml). All patients showed clinical improvement based upon the results of pulmonary function tests and an acute clinical efficacy score (median pre 49/post 60). No patients experienced
drug-related toxicity.
Ciprofloxacin monotherapy is effective for the acute treatment of
cystic fibrosis patients. The development of pathogen resistance during oral
therapy may limit its utility in ambulatory patients.