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A double-blind cross-over study was undertaken to compare the efficacy of amoxycillin and pivampicillin on Haemophilus influenzae infection of the lower respiratory tract in children. 20 patients with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD) due to other causes were included in the study. All patients had a history of regularly harbouring H. influenzae in sputum and repeated treatment failures with pivampicillin. 18 completed two 14-day courses in random order with equimolar doses of pivampicillin (80 mg/kg/day) and amoxycillin (62 mg/kg/day). Both drugs were well tolerated with no serious side effects, but pivampicillin was associated with more pronounced nausea. In steady state the mean serum concentrations of antibiotics 2 and 4 h after medication were 9.7 and 3.7 micrograms/ml for pivampicillin and 19.1 and 7.9 micrograms/ml for amoxycillin (p less than 0.01). Eradication of H. influenzae and clinical improvement was seen in one-third of the courses with both drugs. Betalactamase producing ampicillin-resistant strains emerged during 58% of the amoxycillin courses, but only in 16% of the pivampicillin courses (p less than 0.001). The high number of treatment failures and the development of resistant strains indicate that betalactamase inhibitors may possibly improve the efficacy of these drugs, especially of amoxycillin, in these patients.