Johansen H K, Børch K, Espersen F, Koch C, Høiby N
Department of Clinical Microbiology, H:S Rigshospitalet, Copenhagen, Denmark.
Curr Med Res Opin. 1999;15(4):300-9. doi: 10.1185/03007999909116501.
A prospective, randomised, single-blind comparative trial was carried out to determine whether double beta-lactam treatment with pivampicillin plus pivmecillinam is more effective than pivampicillin alone in the treatment of recurrent and chronic lung infections with Haemophilus influenzae in patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Fifty-six children and young adults with COPD or CF were randomised to the clinical 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 the antibiotic concentrations in serum and sputum after a single dose of each drug. The clinical study showed no significant differences in clinical scoring, lung function tests or adverse events after treatment with pivampicillin plus pivmecillinam or pivampicillin alone. Follow-up microbiological evaluation 2 and 6 weeks after the end of treatment showed that the offending pathogen was eradicated in 68% of the patients treated with pivampicillin plus pivmecillinam and in 67% of the patients treated with pivampicillin alone. Reinfection with another biotype was more common in the combination group (50% vs. 21%) than in the pivampicillin group. In the pharmacokinetic study the median peak serum concentration occurred two hours after intake of tablets. The efficacy of double beta lactam treatment in lung infections with H. influenzae appears to be equivalent to that of ampicillin on clinical lung symptoms, lung function tests, adverse effects and bacteriology.
开展了一项前瞻性、随机、单盲对照试验，以确定在治疗慢性阻塞性肺疾病（COPD）或囊性纤维化（CF）患者的复发性和慢性流感嗜血杆菌肺部感染时，匹氨西林加匹美西林双β-内酰胺治疗是否比单用匹氨西林更有效。56名患有COPD或CF的儿童和青年被随机纳入临床研究。患者被随机分配口服以下药物，为期14天：匹美西林40mg/kg/天加匹氨西林50mg/kg/天，或单用匹氨西林50mg/kg/天。在10名CF患者中进行了一项使用相同药物的交叉药代动力学研究，以确定每种药物单剂量给药后血清和痰液中的抗生素浓度。临床研究表明，匹氨西林加匹美西林或单用匹氨西林治疗后，临床评分、肺功能测试或不良事件方面无显著差异。治疗结束后2周和6周的随访微生物学评估显示，在接受匹氨西林加匹美西林治疗的患者中，68%的患者致病病原体被根除，而在接受单用匹氨西林治疗的患者中这一比例为67%。联合治疗组再次感染另一种生物型的情况比匹氨西林组更常见（50%对21%）。在药代动力学研究中，血清峰值浓度中位数在服用片剂后两小时出现。在临床肺部症状、肺功能测试、不良反应和细菌学方面，双β-内酰胺治疗流感嗜血杆菌肺部感染的疗效似乎与氨苄西林相当。
