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The pharmacokinetic characteristics of ciprofloxacin were studied in 10 children with cystic fibrosis, aged from 6 to 16 years, who had completed the standard regimen of intravenous ceftazidime and amikacin. The aim of the investigation was to derive dosing guidelines for young cystic fibrosis patients to be treated with ciprofloxacin. Each child received ciprofloxacin given as two 30-min infusions (10 mg/kg of body weight each) 12 h apart; this was followed by the administration of oral ciprofloxacin (15 mg/kg every 12 h). Blood samples were taken after both infusions and after the first oral dose. A total of 232 ciprofloxacin concentrations (203 concentrations in plasma and 29 concentrations in urine) were analyzed by use of NONMEM and a twocompartment body model with seven parameters: total body clearance (CL), volume of the central compartment (V 2 ), volume of the peripheral compartment (V 3 ), intercompartmental clearance, renal clearance, absorption rate constant, and bioavailability. The influences of weight (range, 18 to 42 kg) and age (range, 6 to 16 years) were investigated. CL (in liters per hour) was found to be linearly correlated with weight (typical value of CL ‫؍‬ 8.8 ؉ 0.396 ⅐ WT, where WT is weight; (interindividual coefficient of variation, 7.8%). V 2 and V 3 were directly proportional to weight, with slopes of 0.7 and 1.3 liters/kg, respectively. Interindividual variabilities were calculated to be 22.6 and 14.9% for V 2 and V 3 , respectively. No dependency of the other pharmacokinetic parameters on age or weight was seen. Because of the high correlations between age and weight, only one covariable was necessary. Weight had the strongest effect. Bioavailability (population mean) was estimated to be 61.8%, and renal clearance (population mean) was estimated to be 11.4 liters/h. The residual (intraindividual) variability was 31.9%. The protein binding was about 34%, which is similar to the results obtained for adults. In order to define the appropriate dosage regimen for children suffering from cystic fibrosis, a formula was derived so that steady-state concentrations, similar to those obtained in adults after the administration of dosages of 400 mg three times daily intravenously and 750 mg twice daily orally, could be reached. The calculated total daily dose increased with increasing body weight. Given as milligrams per kilogram of body weight, the calculated dosage regimens suggest that for younger children (weight range, 14 to 28 kg), 28 to 20 mg/kg orally twice daily should be given, and for older children (weight range, 28 to 42 kg), 20 to 15 mg/kg orally twice daily should be given. For intravenous administration, dosages of 15 to 10 mg/kg twice daily are sufficient.

The long-term safety and immunogenicity of a polyvalent Pseudomonas aeruginosa conjugate vaccine was evaluated in 30 noncolonized cystic fibrosis patients. Four doses were administered over 3 years, and patients were followed for a mean of 38 months. No acute or long-term adverse effects were noted. Immunization engendered a significant antibody response to all vaccine components. A decline in titers during year 3 of observation was associated with a marked rise in the isolation of P. aeruginosa. This organism was isolated repeatedly from the respiratory tract of 4 patients and only once from 7 patients. The remaining patients were repeatedly culture-negative. Only 1 patient showed clinical deterioration associated with multiple isolations of P. aeruginosa.Pseudomonas aeruginosa is the leading cause of bronchopulmonary infection in patients with cystic fibrosis (CF) [1]. A substantial proportion of morbidity and mortality in this patient population is the result of recurrent pulmonary exacerbations subsequent to colonization. Rarely can P. aeruginosa be eradicated through antibiotic treatment. Further complicating treatment is the fact that multiply resistant strains often arise after repeated or prolonged drug therapy or prophylaxis.Colonization of the lower respiratory tract by mucoid variants of P. aeruginosa is preceded by infection of the upper respiratory tract by smooth strains [2]. Such natural exposure to P. aeruginosa stimulates a vigorous humoral antibody response to many somatic and extracellular antigens [3,4]. However, such antibodies do not prevent or even ameliorate subsequent infections. In fact, several laboratories [5,6] have noted a positive correlation between elevated anti-P aeruginosa antibody titers and a more severe disease course. This may be the result ofimmune complexes being deposited in the lungs and other organs.Anti-P. aeruginosa lipopolysaccharide (LPS) antibodies acquired after natural exposure are not effective at promoting opsonophagocytic killing [7]. We have found that anti-P. aeruginosa LPS antibodies acquired subsequent to colonization had very low average affinity constants, which These studies have been expanded to include 30 noncolonized patients followed for an average of38 months after vaccination. Various clinical. serologic, and bacteriologic parameters were analyzed. Materials and MethodsOver 31 months, 30 CF patients (13 males, 17 females) aged 1.6-24.0 years (mean, 8.3) were enrolled. All were in good health and clinically stable and had no history of infection with P. aeruginosa. On entry. sputum or throat swabs (or both) were negative for P. aeruginosa.Patients were immunized intramuscularly at O. 2, 12, and 36 months with a low (12.5 J.lg ofO-PS per serotype, n = 19) or a high (25 J.lg of O-PS per serotype, n = 11) dose of octavalent O-PS-toxin A conjugate vaccine [9] that contained the following International Antigen Typing System (IATS) LPS serotypes: 1.2/5.3.4,6,7. 10, and 16. Patients were observed for 60 min after immunization. For assessment of adverse r...

Ciprofloxacin was efficacious, safe and well-tolerated as maintenance antipseudomonal therapy in cystic fibrosis patients. These results suggest further evaluation of ciprofloxacin as an oral maintenance therapy is warranted.

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