2022 年第 1 期 第 17 卷

蒙特卡罗模拟在哌拉西林他唑巴坦治疗新生儿细菌感染性疾病初始给药方案优化中的应用

Application of Monte Carlo simulation on optimizing the initial dosing regimen of piperacillin tazobactam in the treatment of neonatal bacterial infectious diseases

作者：韩冬寇晨李兆娜刘尊杰高正平

英文作者：Han Dong Kou Chen Li Zhaona Liu Zunjie Gao Zhengping

单位：首都医科大学附属北京妇产医院北京妇幼保健院新生儿科，北京100026

英文单位：Department of Neonatology Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing Maternal and Child Health Care Hospital Beijing 100026 China

关键词：新生儿细菌感染；哌拉西林他唑巴坦；蒙特卡罗模拟

英文关键词：Neonatalbacterialinfection;Piperacillintazobactam;MonteCarlosimulation

• 摘要：

• 目的 应用蒙特卡罗模拟优化哌拉西林他唑巴坦在新生儿细菌感染性疾病中的初始给药方案，为临床合理制定方案提供参考。方法 回顾性分析2021年1—4月于首都医科大学附属北京妇产医院新生儿重症监护病房住院应用哌拉西林他唑巴坦治疗的新生儿细菌感染性疾病患儿的临床资料。依据注射用哌拉西林钠他唑巴坦钠的药物说明书，制定18种不同初始给药方案，结合对敏感菌的最小抑菌浓度(MIC)的敏感折点，运用蒙特卡罗模拟分析不同给药方案的目标获得概率(PTA)。所有患儿均采用注射用哌拉西林钠他唑巴坦钠100 mg/kg、每8小时1次静脉滴注1 h的给药方案，拟定疗程为7~14 d。分析治疗期间患儿临床资料、辅助检查及治疗效果。结果 蒙特卡罗模拟结果显示,当MIC=0.25 mg/L时，所有给药方案PTA＞90%；当MIC=2 mg/L时，除所有每12小时1次给药方案外，其余给药方案PTA＞90%；当MIC=16 mg/L时，当前制定的给药方案均不能满足PTA＞90%。本研究共纳入33例患儿，其中新生儿宫内感染9例、新生儿肺炎24例。治疗后临床评估有效为33例，症状缓解时间为（1.2±0.6）d，新生儿白细胞计数、中性粒细胞百分比、C反应蛋白、血肌酐水平较治疗前均明显降低（均P＜0.001），血小板计数、丙氨酸转氨酶水平与治疗前比较差异均无统计学意义（均P＞0.05）。结论  蒙特卡罗模拟结果显示哌拉西林他唑巴坦在新生儿细菌感染性疾病的初始给药方案应为100 mg/kg、每8小时1次静脉滴注1 h。临床应用结果表明，该给药方案针对敏感细菌治疗有效，且未见明显不良反应。

• Objective   To apply Monte Carlo simulation on optimizing the initial dosing regimen of piperacillin tazobactam in the treatment of neonatal bacterial infectious diseases, so as to provide a reference for clinically reasonable formulation of the regimen. Methods  Clinical data of children with neonatal bacterial infectious diseases admitted to Pediatric Intensive Care Unit, Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January to April 2021 were retrospectively analyzed. According to the drug instruction of piperacillin sodium and tazobactam sodium for injection, 18 different initial dosing regimens were formulated. The sensitive breakpoint to the minimal inhibitory concentration (MIC) of sensitive bacteria was determined and Monte Carlo simulation was used to analyze probability of target acquisition (PTA). All the children were treated with piperacillin sodium and tazobactam sodium for injection 100 mg/kg, intravenous infusion for 1 h every 8 h dosing regimen, and the proposed treatment course was 7-14 d. The clinical data, auxiliary examinations during the course of treatment and curative effect of children were analyzed. Results  Monte Carlo simulation showed that, as MIC=0.25 mg/L, all dosing regimens had PTA>90%; as MIC=2 mg/L, except 1 time every 12 h dosing regimens, all dosing regimens had PTA>90%; as MIC=16 mg/L, the current none of the formulations of dosing regimens had PTA>90%. There were 33 cases of children were enrolled, including 9 cases of neonatal intrauterine infection and 24 cases of neonatal pneumonia. After treatment, the clinical evaluation of 33 cases was effective, and symptom relief time was (1.2±0.6)d. After treatment, white blood cell count, percentage of neutrophils, C-reactive protein and serum creatinine levels were significantly lower than those before treatment (all P<0.001), and there were no significant differences in platelet count and alanine aminotransferase level compared to those before treatment(both P>0.05). Conclusions  The Monte Carlo simulation showed that the initial dosing regimen of piperacillin tazobactam for neonatal bacterial infectious diseases is 100 mg/kg， intravenous infusion for 1 h every 8 h. Through clinical practical applications, this dosing regimen is effective for sensitive bacterial therapy, and no obvious adverse reactions have occurred.??