Milner R D, Ross J, Froud D J, Davis J A
Arch Dis Child. 1972 Dec;47(256):927-32. doi: 10.1136/adc.47.256.927.
Newborn infants with suspected bacterial infection were treated with intramuscular gentamicin. Serum levels of the drug were measured 1 hour after the first dose, immediately before the second dose, and immediately before and 1 hour after a dose given on the third day. On a low dosage regimen (1 mg/kg every 8 hours) 9 of 17 infants had serum gentamicin levels below the required minimum level of 1 μg/ml immediately before the second dose, and 5 of 19 infants had similarly low levels on the third day. On a high dosage regimen (3 mg/kg initially, then 2 mg/kg every 8 hours) 2 of 10 infants had preinjection serum gentamicin levels below 1 μg/ml on the first day, and 3 out of 16 had similar levels on the third day. The mean (± SE) serum gentamicin level on the high dosage regimen was 5·0 ± 0·5 μg/ml 1 hour after the first injection, 1·9 ± 0·4 μg/ml just before the second injection, and on the third day 1·9 ± 0·3 μg/ml just before an injection and 5·1 ± 0·5 μg/ml 1 hour after injection. The highest serum gentamicin level recorded in any of the 40 infants studied was 8·2 μg/ml. On the first day of treatment with the low dose regimen, a mean of 21% (range 9-68%) of the injected dose was recovered from the urine; and on the third or fourth day a mean of 44% (range 17-76%) of the gentamicin injected on that day was recovered. In 4 infants who died tissue gentamicin levels were measured in the liver, lungs, heart, kidneys, and brain, the highest concentration being in the kidney with low levels in the heart, liver, and brain, while levels in the lungs were intermediate. Neonatal renal and pulmonary infections are thus likely to be suitably treated with gentamicin. Bacteriological studies confirmed the effectiveness of gentamicin in the treatment of neonatal infection, but a dosage regimen derived by extrapolation from older children frequently resulted in inadequate serum levels, and a higher dosage regimen giving more satisfactory results was therefore defined.
疑似细菌感染的新生儿接受了庆大霉素肌肉注射治疗。在首次给药后1小时、第二次给药前即刻、第三天给药前即刻及给药后1小时测量血清药物水平。在低剂量方案（每8小时1mg/kg）下，17名婴儿中有9名在第二次给药前血清庆大霉素水平低于所需的最低水平1μg/ml，19名婴儿中有5名在第三天时血清水平同样较低。在高剂量方案（初始剂量3mg/kg，然后每8小时2mg/kg）下，10名婴儿中有2名在第一天注射前血清庆大霉素水平低于1μg/ml，16名婴儿中有3名在第三天时血清水平同样较低。高剂量方案下，首次注射后1小时血清庆大霉素平均（±SE）水平为5.0±0.5μg/ml，第二次注射前为1.9±0.4μg/ml，第三天注射前为1.9±0.3μg/ml，注射后1小时为5.1±0.5μg/ml。在研究的40名婴儿中，记录到的最高血清庆大霉素水平为8.2μg/ml。在低剂量方案治疗的第一天，从尿液中回收的注射剂量平均为21%（范围9 - 68%）；在第三天或第四天，当天注射的庆大霉素平均回收量为44%（范围17 - 76%）。对4名死亡婴儿的肝脏、肺、心脏、肾脏和大脑进行了组织庆大霉素水平测量，最高浓度出现在肾脏，心脏、肝脏和大脑中的水平较低，而肺中的水平处于中间值。因此，庆大霉素可能适用于新生儿肾脏和肺部感染的治疗。细菌学研究证实了庆大霉素治疗新生儿感染的有效性，但从大龄儿童推断得出的剂量方案常常导致血清水平不足，因此确定了能产生更满意结果的更高剂量方案。
