Rappaz I, Decosterd L A, Bille J, Pilet M, Bélaz N, Roulet M
Department of Paediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Eur J Pediatr. 2000 Dec;159(12):919-25. doi: 10.1007/pl00008370.
Continuous infusion (CI) of beta-lactam antibiotics provides a stable concentration which may result in a better activity against gram-negative bacteria if exceeding the minimum inhibitory concentration (MIC). Treatment outcome after 24 h CI of ceftazidime (CAZ) in cystic fibrosis (CF) children was compared with the bolus administration regimen. Fourteen CF children with chronic Pseudomonas aeruginosa pulmonary infection were treated during 14 days with the conventional CAZ thrice-a-day bolus infusion (regimen A), and few months later with 24 h Cl of CAZ (regimen B) using a portable pump. Amikacin was added to both regimens. Clinical efficacy of treatment was assessed using pulmonary, inflammatory and nutritional variables. Bacteriological analyses and CAZ concentrations in serum and sputum were also measured. All patients improved clinically with both regimens. Among the parameters used to compare both regimens, only prealbumin values improved (regimen A: + 0.08 g/l versus regimen B: +0.11 g/l P = 0.015). No clinically significant side-effects were noted. In regimen A, the mean predose (trough level) CAZ concentration in serum was highly variable (range 2.2-45.4 gg/ml) with some values (32% of samples) below the MIC of P. aeruginosa isolates found in the sputum of the patients. In regimen B, the serum CAZ level achieved was 28.5+/-8.4 microg/ml without any value below the MIC. The mean sputum levels were comparable in both regimens. No CAZ resistant strains of P. aerugino.sa appeared between and directly after the treatments.
The clinical outcome of children with cystic fibrosis treated with 24 h continuous infusion of ceftazidime was no different from that achieved with the conventional bolus infusion regimen. Continuous infusion provided a sustained serum ceftazidime level well above the P. aeruginosa minimum inhibitory concentration. Continuous infusion was well tolerated and appreciated by the children and this may promote home therapy for cystic fibrosis children.
持续输注(CI)β-内酰胺类抗生素可提供稳定的血药浓度,若超过最低抑菌浓度(MIC),可能对革兰氏阴性菌产生更好的抗菌活性。比较了头孢他啶(CAZ)持续输注24小时对囊性纤维化(CF)儿童的治疗效果与大剂量给药方案。14例患有慢性铜绿假单胞菌肺部感染的CF儿童,先接受为期14天的传统CAZ每日三次大剂量输注治疗(方案A),数月后使用便携式泵进行CAZ 24小时持续输注治疗(方案B)。两种方案均加用阿米卡星。通过肺部、炎症和营养变量评估治疗的临床疗效。还测定了血清和痰液中的细菌学分析及CAZ浓度。两种方案治疗后所有患者临床症状均有改善。在用于比较两种方案的参数中,只有前白蛋白值有所改善(方案A:增加0.08 g/l,方案B:增加0.11 g/l,P = 0.015)。未观察到具有临床意义的副作用。在方案A中,血清中CAZ的平均给药前(谷浓度)浓度变化很大(范围为2.2 - 45.4 μg/ml),部分值(32%的样本)低于患者痰液中分离出的铜绿假单胞菌的MIC。在方案B中,达到的血清CAZ水平为28.5±8.4 μg/ml,无任何值低于MIC。两种方案的痰液平均水平相当。治疗期间及治疗后均未出现对CAZ耐药的铜绿假单胞菌菌株。
囊性纤维化儿童接受头孢他啶24小时持续输注的临床疗效与传统大剂量输注方案无异。持续输注可使血清头孢他啶水平持续维持在远高于铜绿假单胞菌最低抑菌浓度的水平。持续输注耐受性良好,儿童易于接受,这可能会促进囊性纤维化儿童的家庭治疗。