He Xin, Liu Xiaoyan, Gong Xiaodan, Wang Li, Chen Feng
Department of Pharmacy, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.
Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China.
Curr Drug Metab. 2023;24(1):5-15. doi: 10.2174/1389200224666230325121729.
Meropenem, as a carbapenem antibiotic, is commonly used in critically ill pediatric patients with severe infection because of its broad antimicrobial spectrum, high penetration into tissues, and favorable safety profile. Due to pathophysiological changes in critically ill children, the available evidence has demonstrated that the standard dosage regimens of meropenem could not meet an appropriate pharmacodynamic (PD) target attainment in severely infected children. Therefore, we reviewed the pharmacokinetic (PK) profile of meropenem in critically ill children, therapeutic drug monitoring (TDM), and dose optimization based on PK/PD. Meropenem kills bacteria in a timedependent manner and its efficacy is positively correlated with the percentage of the time of dosing interval during which the free serum concentration of meropenem remains above the minimum inhibitory concentration (MIC) of the pathogen (%fT>MIC), which is related to PK/PD targets. For critically ill children, TDM-based dosage optimization and setting even higher PK/PD targets seem necessary to be considered. The currently available studies have revealed that increasing the dose and the application of the extended or continuous infusion of meropenem were able to achieve better PK/PD targets. According to limited clinical data on efficacy and safety, these treatment measures cannot yet be adopted as routine regimens only when serious infections caused by drug-resistant bacteria or strains with high values of MIC are suspected. Further high-quality randomized controlled trials (RCTs) or observational studies with sufficient sample sizes are required to confirm the efficacy and safety of these modes of administration.
美罗培南作为一种碳青霉烯类抗生素，因其抗菌谱广、组织穿透力强和安全性良好，常用于患有严重感染的危重症儿科患者。由于危重症儿童的病理生理变化，现有证据表明美罗培南的标准给药方案无法使严重感染儿童达到合适的药效学（PD）目标。因此，我们回顾了美罗培南在危重症儿童中的药代动力学（PK）特征、治疗药物监测（TDM）以及基于PK/PD的剂量优化。美罗培南以时间依赖性方式杀灭细菌，其疗效与给药间隔时间内美罗培南游离血清浓度高于病原体最低抑菌浓度（MIC）的时间百分比（%fT>MIC）呈正相关，这与PK/PD目标相关。对于危重症儿童，基于TDM的剂量优化以及设定更高的PK/PD目标似乎有必要加以考虑。目前的研究表明，增加美罗培南的剂量以及采用延长输注或持续输注能够实现更好的PK/PD目标。根据有限的疗效和安全性临床数据，仅在怀疑由耐药菌或MIC值高的菌株引起严重感染时，这些治疗措施尚不能作为常规方案采用。需要进一步开展高质量的随机对照试验（RCT）或样本量充足的观察性研究来证实这些给药方式的疗效和安全性。
