Arguedas A G, Stutman H R, Zaleska M, Knupp C A, Marks M I, Nussbaum E
Pediatric Infectious Disease, Division, Memorial Miller Children's Hospital, Long Beach, Calif. 90801-1428.
Am J Dis Child. 1992 Jul;146(7):797-802. doi: 10.1001/archpedi.1992.02160190029013.
To measure first-dose and steady-state plasma, urine, and sputum concentrations of cefepime and make preliminary assessments of the clinical efficacy of cefepime in patients with cystic fibrosis.
Open noncomparative clinical trial.
Memorial Miller Children's Hospital of Long Beach, Calif.
Twelve patients, aged 4 to 41 years, with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary infections.
Patients received cefepime at 50 mg/kg per dose (maximum dose, 2 g per dose) given intravenously every 8 hours. Clinical evaluations, pulmonary function tests, quantitative sputum cultures, and sensitivity testing were performed before, at the end of, and 2 weeks after therapy.
Mean (+/- SD) peak plasma concentrations after the first dose were 148.2 (36.6) mg/L; the following other values were included: half-life, 1.59 (0.46) hours; area under the curve, 292 (94) microgram/h per milliliter; total-body clearance, 3.01 (1.46) mL/min per kilogram; volume of distribution at steady state, 0.32 (0.10) L/kg; and percent of dose recovered in urine, 52% (27%). Steady-state and first-dose values were similar. Trough levels varied from 6.4 to 7.2 mg/L. Mean (+/- SD) sputum concentrations at steady state varied from 6.3 (5.4) to 4.8 (2.3) mg/L. At completion of therapy, nine of 10 patients' conditions were improved as indicated by clinical scores (greater than 10 points), forced vital capacity (greater than 10%), and a greater than or equal to 1 log decrease in sputum bacterial concentration. Cefepime was well tolerated in 10 patients, but rash and light-headedness developed in two patients. Pseudomonas aeruginosa minimum inhibitory concentration90 increased from the start (64 mg/L) to the end of therapy (256 mg/L) and was unchanged 2 weeks later.
Based on these data and the potential advantage of a single agent for the treatment of mixed infections (Staphylococcus aureus and P aeruginosa), comparative clinical trials of cefepime and standard therapy for bronchopulmonary exacerbations in patients with cystic fibrosis appear to be warranted.
测定头孢吡肟的首剂及稳态血浆、尿液和痰液浓度，并对头孢吡肟治疗囊性纤维化患者的临床疗效进行初步评估。
开放性非对照临床试验。
加利福尼亚州长滩市纪念米勒儿童医院。
12例年龄在4至41岁之间、确诊为囊性纤维化并患有慢性支气管肺部感染的患者。
患者每8小时静脉注射一次头孢吡肟，剂量为50mg/kg（最大剂量为每剂2g）。在治疗前、治疗结束时及治疗后2周进行临床评估、肺功能测试、定量痰液培养和药敏试验。
首剂后血浆峰浓度均值（±标准差）为148.2（36.6）mg/L；其他数值如下：半衰期为1.59（0.46）小时；曲线下面积为292（94）μg/h每毫升；总体清除率为3.01（1.46）mL/min每千克；稳态分布容积为0.32（0.10）L/kg；尿液中回收剂量的百分比为52%（27%）。稳态值和首剂值相似。谷浓度在6.4至7.2mg/L之间。稳态时痰液浓度均值（±标准差）在6.3（5.4）至4.8（2.3）mg/L之间。治疗结束时，根据临床评分（大于10分）、用力肺活量（大于10%）以及痰液细菌浓度下降大于或等于1个对数，10例患者中有9例病情改善。10例患者对头孢吡肟耐受性良好，但有2例患者出现皮疹和头晕。铜绿假单胞菌的最低抑菌浓度90从治疗开始时的64mg/L升至治疗结束时的256mg/L，2周后未发生变化。
基于这些数据以及单一药物治疗混合感染（金黄色葡萄球菌和铜绿假单胞菌）的潜在优势，开展头孢吡肟与囊性纤维化患者支气管肺部病情加重的标准治疗方法的对比临床试验似乎是必要的。
