Randomised trial of pivampicillin plus pivmecillinam vs. pivampicillin in children and young adults with chronic obstructive pulmonary disease and infection with Haemophilus influenzae

A prospective, randomised, single-blind comparative trial was carried out t o determine whether double beta-lactam with pivampicillin plus pivmecillina m is more effective than pivampicillin alone in the treatment of recurrent and chronic lung infections with Haemophilus influenzae in patients with ch ronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Fifty-s ix children and young adults with COPD or CF were randomised to the clinica l study. The patients were allocated at random to receive perorally either pivmecillinam, 40 mg/kg/day, combined with pivampicillin, 50 mg/kg/day, or pivampicillin 50 mg/kg/day alone for 14 days. A cross-over pharmacokinetic study using the same drugs was carried out in 10 CF patients to determine t he antibiotic concentrations in serum and sputum after a single dose of eac h drug. The clinical study showed no significant differences in clinical sc oring, lung function tests or adverse events after treatment with pivampici llin plus pivmecillinam or pivampicillin alone. Follow-up microbiological e valuation 2 and 6 weeks after the end of treatment showed that the offendin g pathogen was eradicated in 68% of the patients treated with pivampicillin plus pivmecillinam and in 67% of the patients treated with pivampicillin a lone. Reinfection with another biotype was more common in the combination g roup (50% vs. 21%) than in the pivampicillin group. In the pharmacokinetic study the median peak serum concentration occurred two hours after intake o f tablets. The efficacy of double beta-lactam treatment in lung infections with H. inf luenzae appears to be equivalent to that of ampicillin on clinical lung sym ptoms, lung function tests, adverse effects and bacteriology.