Azagami S, Kusumoto Y, Oikawa T, Osano M, Shiro H, Shirai Y, Nakamura M
Department of Pediatrics, School of Medicine, Keio University.
Jpn J Antibiot. 1988 Nov;41(11):1704-14.
Clinical pharmacology and clinical efficacy and safety of imipenem/cilastatin sodium (IPM/CS), a beta-lactam antibiotic with a carbapenem nucleus and a dehydropeptidase-I inhibitor, were investigated in newborns. 1. Peak serum concentrations of IPM/CS at a dose of 20 mg/20 mg/kg were achieved at the end of 60-minute infusion. Maximum serum levels of IPM and CS were 44.2 micrograms/ml and 70.0 micrograms/ml, respectively, in neonates with ages 0-3 days. IPM and CS peak levels in premature infants with ages 0-3 days were 47.2 micrograms/ml and 56.1 micrograms/ml, respectively. IPM and CS peak levels in neonates 4 day-old or older were 35.0 micrograms/ml and 41.5 micrograms/ml, respectively, and in premature infants of similar ages were 45.7 micrograms/ml and 65.3 micrograms/ml, respectively. 2. Mean serum half-lives of IPM and CS in 0-3 day-old neonates were 1.6 hours and 3.1 hours, respectively, and the mean serum half-lives in premature infants were 2.1 hours and 4.6 hours, respectively. In neonates 4 day-old or older, the mean serum half-lives of IPM and CS were 1.6 hours and 2.6 hours, respectively, and in premature infants they were 1.5 hours and 1.9 hours, respectively. 3. A dose response was evident between doses of 10 mg/10 mg/kg and 20 mg/20 mg/kg of IPM and CS. 4. Urinary recovery rates of IPM for the 0- to 6-hour post IPM/CS infusion period ranged between 27.2 and 46.6%. For CS, urinary recovery rates for the 0- to 6-hour post IPM/CS infusion period ranged between 25.3 and 100.8%. 5. Clinical efficacy was evaluated in 9 patients and 7 patients showed excellent or good responses. 6. Of 14 patients who received IPM/CS treatment, 1 patient showed hematuria, leukopenia and thrombocytopenia, and 3 patients showed eosinophilia. However, these adverse reactions improved after the completion of therapy. 7. IPM has excellent antimicrobial activity against aerobic and anaerobic Gram-positive and Gram-negative bacteria. In this study, coadministration of IPM and CS produced good clinical responses and no serious adverse reactions. It is hence concluded that IPM/CS sodium is very useful for the treatment of severe bacterial infections in neonates, especially in the presence of beta-lactamase resistant strains and in polymicrobial infections.
对具有碳青霉烯核和脱氢肽酶-I抑制剂的β-内酰胺抗生素亚胺培南/西司他丁钠（IPM/CS）在新生儿中的临床药理学、临床疗效和安全性进行了研究。1. 以20mg/20mg/kg的剂量给药时，IPM/CS在60分钟输注结束时达到血清峰值浓度。在0至3天的新生儿中，IPM和CS的最高血清水平分别为44.2微克/毫升和70.0微克/毫升。0至3天的早产儿中，IPM和CS的峰值水平分别为47.2微克/毫升和56.1微克/毫升。4天及以上的新生儿中，IPM和CS的峰值水平分别为35.0微克/毫升和41.5微克/毫升，类似年龄的早产儿中，IPM和CS的峰值水平分别为45.7微克/毫升和65.3微克/毫升。2. 0至3天的新生儿中，IPM和CS的平均血清半衰期分别为1.6小时和3.1小时，早产儿中的平均血清半衰期分别为2.1小时和4.6小时。在4天及以上的新生儿中，IPM和CS的平均血清半衰期分别为1.6小时和2.6小时，在早产儿中分别为1.5小时和1.9小时。3. 在10mg/10mg/kg至20mg/20mg/kg的IPM和CS剂量之间存在明显的剂量反应。4. 在IPM/CS输注后0至6小时期间，IPM的尿回收率在27.2%至46.6%之间。对于CS，IPM/CS输注后0至6小时期间的尿回收率在25.3%至100.8%之间。5. 对9例患者的临床疗效进行了评估，7例患者显示出优秀或良好的反应。6. 在接受IPM/CS治疗的14例患者中，1例出现血尿、白细胞减少和血小板减少，3例出现嗜酸性粒细胞增多。然而，这些不良反应在治疗结束后有所改善。7. IPM对需氧和厌氧革兰氏阳性及革兰氏阴性细菌具有优异的抗菌活性。在本研究中，IPM和CS联合给药产生了良好的临床反应，且无严重不良反应。因此得出结论，亚胺培南/西司他丁钠对治疗新生儿严重细菌感染非常有用，尤其是在存在β-内酰胺酶耐药菌株和混合感染的情况下。
