a Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences , University of the Witwatersrand , Johannesburg , South Africa.
b Global Antibiotic Research and Development Partnership (GARDP) , Drugs for Neglected Diseases initiative , Geneva , Switzerland.
Expert Opin Pharmacother. 2019 Mar;20(4):415-422. doi: 10.1080/14656566.2018.1559817. Epub 2018 Dec 21.
The incidence of healthcare-associated multidrug resistant bacterial infections, particularly due to carbapenem resistant organisms, has been on the rise globally. Among these are the carbapenem resistant Acinetobacter baumannii and Enterobacteriaceae, which have been responsible for numerous outbreaks in neonatal units. The polymyxins (colistin and polymyxin B) are considered to be the last resort antibiotics for treating such infections. However, pharmacokinetic and pharmacodynamic data on the use of polymyxins in neonates and children are very limited, and there are safety concerns.
In this review, the authors summarize the global burden of multidrug resistance, particularly carbapenem resistance, in the neonatal and paediatric population, and the potential wider use of polymyxins in treating these infections.
Both colistin and polymyxin B have similar efficacy in treating multidrug resistant infections but have safety concerns. However, polymyxin B appears to be a better therapeutic option, with more rapid and higher steady state concentrations achieved compared to colistin and less reported nephrotoxicity. There is virtually no data in neonates and children currently; there is therefore an urgent need for pharmacokinetic and safety trials in these populations to determine the optimal drug and dosing regimens and provide recommendations for their use against carbapenem resistant infections.
全球范围内，与医疗相关的多重耐药菌感染（尤其是碳青霉烯类耐药菌）的发病率一直在上升。其中包括碳青霉烯类耐药鲍曼不动杆菌和肠杆菌科细菌，这些细菌已导致新生儿病房发生了多起暴发事件。多粘菌素（黏菌素和多粘菌素 B）被认为是治疗此类感染的最后手段抗生素。然而，关于多粘菌素在新生儿和儿童中的药代动力学和药效学数据非常有限，并且存在安全性问题。
在这篇综述中，作者总结了全球新生儿和儿科人群中多重耐药（尤其是碳青霉烯类耐药）的负担，以及多粘菌素在治疗这些感染中的潜在更广泛应用。
黏菌素和多粘菌素 B 在治疗多重耐药感染方面具有相似的疗效，但存在安全性问题。然而，与黏菌素相比，多粘菌素 B 似乎是一种更好的治疗选择，它能更快达到更高的稳态浓度，且报告的肾毒性较低。目前在新生儿和儿童中几乎没有数据；因此，迫切需要在这些人群中进行药代动力学和安全性试验，以确定最佳药物和剂量方案，并针对碳青霉烯类耐药感染提供使用建议。
