Study design (if review, criteria of inclusion for studies)
RCT Parallel design. Multi centre (15 centres in 9 countries).
Participants
108 people randomised (55 to oral CPX and 53 to parenteral combination therapy). Minimum age of 5 years and whose growth was not completed, hospitalised between May 1993 and April 1995, for treatment of an exacerbation of pulmonary infection. Treatment was confined to those who were infected with P. aeruginosa. Mean age in CPX group: 10.2 years; in combination therapy group: 11.00 years. Age across groups ranged from 5 to 17 years. Sex: 59 males, 49 females in each group. CPX group (32 males, 23 females); combination therapy group (27 males, 26 females). Country: 9 countries.
Interventions
Each treatment given for 14 days. Oral CPX (15mg/kg bd, maximum dose, 1500 mg/day) versus IV ceftazidine plus tobramycin (50mg/kg tds, 3mg/kg tds, respectively). The dosage was adjusted to achieve to achieve peak plasma concentrations between 6 & 12 mg/l and trough values <2 mg/l. Time-points when measurements were taken during the trial: at baseline, at 5 to 7 days, at 14 days and at follow up (20 to 30 days). Time-points reported in the trial: baseline, day 14 and follow up (day 20 to 30) data.
Outcome measures
Shwachman score Chest radiographs (using Chrispin-Norman score) Laboratory assessments (Days 5 to 7, chemistry) and at the end of therapy (all) and at follow-up (haematology) Adverse events Additional antibiotics for new acute exacerbations* Severity of acute exacerbations was assessed by a modified acute change clinical score system FEV1 (% of predicted value for height)* FVC (% of predicted value for height)* Physical examination of the joints (knees, hips, shoulders) assessed four times* MRI evaluation Baseline sputum samples were taken 48 hr before treatment. Bacteriologic outcome at the end of treatment and at follow up.
Main results
Clinical improvement was observed in 93% of patients treated with oral ciprofloxacin and in 96% of those receiving parenteral therapy. Transient suppression of Pseudomonas aeruginosa was achieved in 63% of patients at the end of the course of iv CAZ/TM therapy and in 24% receiving ciprofloxacin. Ultrasound examination and nuclear magnetic resonance imaging scans showed no evidence of cartilage toxicity in any of the ciprofloxacin-treated patients. Musculoskeletal adverse events were reported with similar frequency in the two groups of patients (7% in the group receiving ciprofloxacin therapy and 11% in the IV CAZ/TM group). The only sustained musculoskeletal symptom was a case of synovitis in a patient receiving parenteral CAZ/TM.
Authors' conclusions
Ciprofloxacin thus appears to be safe and effective for use in young patients with bronchopulmonary exacerbation of cystic fibrosis.