Hashira S, Koike Y, Fujii R
Jpn J Antibiot. 1982 Jul;35(7):1737-48.
Fundamental and clinical investigations of cefotaxime were carried out in neonates. The following results were obtained. 1. Seven neonates with serious infections caused by identifiable pathogens, including Group B streptococcal meningitis and Group A streptococcal sepsis, were treated by intravenous bolus injection of 20-200 mg/kg of cefotaxime 2 or 3 times daily (60-400 mg/kg/day). The clinical efficacy of cefotaxime was assessed to be good in 6 patients and fair in 1 patient. Bacteriological efficacy was evaluable in 4 patients, all of whom displayed complete eradication of pathogens. 2. Among 22 neonates administered cefotaxime, adverse reactions appeared in 3 patients. Adverse reactions consisted of a transient skin rash in 1 patient and elevation of GOT in 2 patients. 3. Serum concentrations of cefotaxime and desacetyl cefotaxime were investigated in 8 mature infants and 5 immature infants on days 0-7 postpartum. A single intravenous injection of 20 mg/kg produced peak serum concentrations of 31.8-49.7 mcg/ml, associated with a half-life of 1.38-4.47 hours, in mature infants and peak serum concentrations of 35.5-55.0 mcg/ml, associated with a half-life of 3.22-6.43 hours, in immature infants. On days 0-2 postpartum the half-life was longer than on subsequent days. This tendency was particularly remarkable in immature infants. Serum concentrations of desacetyl cefotaxime displayed high individual variations; no consistent trends were noted. 4. Cefotaxime and desacetyl cefotaxime serum concentrations were studied in 3 neonates undergoing exchanged transfusion (exchanged volume 177-180 ml/kg) on 1-4 days postpartum. Serum concentrations of cefotaxime after exchanged transfusion were equivalent to 32.6-63.9% of the pretransfusion level, while those of desacetyl cefotaxime were 75.2-106% of the pretransfusion level. 5. Minimal inhibitory concentration (MICs) and minimal bactericidal concentration (MBCs) of cefotaxime were determined against clinical isolates. MICs for inoculum sizes of 10(8)/ml and 10(6)/ml were respectively 3.13-25 mcg/ml and 3.13-25 mcg/ml against S. aureus, 0.024 mcg/ml and 0.012 mcg/ml against Group A Streptococcus, 0.05 mcg/ml and 0.05 mcg/ml against Group B Streptococcus and 0.39 mcg/ml and 0.1 mcg/ml against E. coli. MBCs for an inoculum size of 10(6)/ml were 3.13-100 mcg/ml or over against S. aureus, 0.012 mcg/ml against Group A Streptococcus, 0.39 mcg/ml against Group B Streptococcus and 1.56 mcg/ml against E. coli.
对新生儿进行了头孢噻肟的基础和临床研究。获得了以下结果。1. 7例由可识别病原体引起严重感染的新生儿，包括B组链球菌脑膜炎和A组链球菌败血症，通过每日静脉推注20 - 200mg/kg头孢噻肟，2或3次（60 - 400mg/kg/天）进行治疗。头孢噻肟的临床疗效评估为6例良好，1例一般。4例患者的细菌学疗效可评估，所有患者病原体均被完全清除。2. 在22例接受头孢噻肟治疗的新生儿中，3例出现不良反应。不良反应包括1例短暂性皮疹和2例谷草转氨酶升高。3. 对8例成熟婴儿和5例未成熟婴儿在产后0 - 7天研究了头孢噻肟和去乙酰头孢噻肟的血清浓度。单次静脉注射20mg/kg后，成熟婴儿的血清峰值浓度为31.8 - 49.7mcg/ml，半衰期为1.38 - 4.47小时；未成熟婴儿的血清峰值浓度为35.5 - 55.0mcg/ml，半衰期为3.22 - 6.43小时。产后0 - 2天的半衰期比后续几天长。这种趋势在未成熟婴儿中尤为明显。去乙酰头孢噻肟的血清浓度个体差异较大；未观察到一致的趋势。4. 对3例产后1 - 4天接受换血（换血量177 - 180ml/kg）的新生儿研究了头孢噻肟和去乙酰头孢噻肟的血清浓度。换血后头孢噻肟的血清浓度相当于输血前水平的32.6 - 63.9%，而去乙酰头孢噻肟的血清浓度为输血前水平的75.2 - 106%。5. 测定了头孢噻肟对临床分离株的最低抑菌浓度（MICs）和最低杀菌浓度（MBCs）。接种量为10(8)/ml和10(6)/ml时，对金黄色葡萄球菌的MICs分别为3.13 - 25mcg/ml和3.13 - 25mcg/ml，对A组链球菌为0.024mcg/ml和0.012mcg/ml，对B组链球菌为0.05mcg/ml和0.05mcg/ml，对大肠杆菌为0.39mcg/ml和0.1mcg/ml。接种量为10(6)/ml时，对金黄色葡萄球菌的MBCs为3.13 - 100mcg/ml或更高，对A组链球菌为0.012mcg/ml，对B组链球菌为0.39mcg/ml，对大肠杆菌为1.56mcg/ml。
