Rao Shripada C, Srinivasjois Ravisha, Hagan Ronald, Ahmed Mohmed
Centre for Neonatal Research and Education, King Edward Memorial Hospital for Women and Princess Margaret Hospital for Children, Perth Western Australia, Australia.
Cochrane Database Syst Rev. 2011 Nov 9(11):CD005091. doi: 10.1002/14651858.CD005091.pub3.
Animal studies and trials in older children and adults suggest that a one dose per day regimen of gentamicin is superior to a multiple doses per day regimen.
To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates.
Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, April 2011), MEDLINE (1966 to April 2011), EMBASE 1980 to April 2011, and CINAHL (December 1982 to April 2011). Abstracts of the Society for Pediatric Research were searched from 1980 to 2010 inclusive.
All randomised or quasi randomised controlled trials comparing one dose per day ( 'once a day') compared to multiple doses per day ( 'multiple doses a day') of gentamicin to newborn infants < 28 days of life.
Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group.
Eleven studies were included (N = 574) and nineteen excluded. All infants in both 'once a day' as well as 'multiple doses a day' regimen showed adequate clearance of sepsis [typical RD 0.00 (95% CI - 0.19 to 0.19); 3 trials; N = 36]. For the other primary outcome measures relating to gentamicin pharmacokinetics 'once a day' dosing of gentamicin was superior. 'Once a day' gentamicin regimen was associated with less failures to attain peak level of at least 5 µg/ml [typical RR 0.22 (95% CI 0.11 to 0.47); 9 trials; N = 422] and less failures to achieve trough levels of < 2 µg/ml [typical RR 0.38 (95% CI 0.27 to 0.55); 11 trials N = 503] compared to 'multiple doses a day' regimen.Ototoxicity and nephrotoxicity were not noted with either of the treatment regimens.
AUTHORS' CONCLUSIONS: There is insufficient evidence from the currently available RCTs to conclude whether 'once a day' or 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggests that pharmacokinetic properties of 'once a day' gentamicin regimen are superior to 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There is no change in nephrotoxicity or auditory toxicity. Based on this assessment of pharmacokinetics, 'once a day regimen' may be superior in treating neonatal sepsis in neonates greater than 32 weeks gestation.
动物研究以及针对大龄儿童和成人的试验表明，庆大霉素每日一剂的给药方案优于每日多剂的给药方案。
比较庆大霉素每日一剂与每日多剂给药方案用于疑似或确诊败血症新生儿的疗效和安全性。
通过检索Cochrane对照试验中心注册库（CENTRAL，Cochrane图书馆，2011年4月）、MEDLINE（1966年至2011年4月）、EMBASE（1980年至2011年4月）和CINAHL（1982年12月至2011年4月）来识别符合条件的研究。检索了1980年至2010年（含）的儿科学会摘要。
所有比较庆大霉素每日一剂（“每日一次”）与每日多剂（“每日多剂”）给药方案用于小于28日龄新生儿的随机或半随机对照试验。
数据收集和分析按照Cochrane新生儿综述组的标准进行。
纳入11项研究（N = 574），排除19项。“每日一次”和“每日多剂”给药方案的所有婴儿败血症清除情况均良好[典型风险差0.00（95%CI - 0.19至0.19）；3项试验；N = 36]。对于其他与庆大霉素药代动力学相关的主要结局指标，庆大霉素“每日一次”给药方案更优。与“每日多剂”给药方案相比，庆大霉素“每日一次”给药方案达到至少5μg/ml峰值水平失败的情况更少[典型相对危险度0.22（95%CI 0.11至0.47）；9项试验；N = 422]，且达到低于2μg/ml谷浓度失败的情况更少[典型相对危险度0.38（95%CI 0.27至0.55）；11项试验；N = 503]。两种治疗方案均未观察到耳毒性和肾毒性。
目前可用的随机对照试验证据不足，无法得出庆大霉素“每日一次”或“每日多剂”给药方案在治疗确诊的新生儿败血症方面哪种更优的结论。然而，数据表明庆大霉素“每日一次”给药方案的药代动力学特性优于“每日多剂”给药方案，因为它能达到更高的峰值水平，同时避免出现毒性谷浓度。肾毒性和听觉毒性无变化。基于这种药代动力学评估，“每日一次给药方案”在治疗孕周大于32周的新生儿败血症方面可能更优。
