Abstract：
The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable β-lactams, standard and high dosages have been proposed for short-infusion regimens only.
To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).
Monte Carlo simulations were performed for seven injectable β-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable.
Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam.
These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary.
To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).
Monte Carlo simulations were performed for seven injectable β-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable.
Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam.
These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary.
摘要：
背景：EUCAST在2020年提出的抗菌药物敏感性类别的新定义要求定义标准和高剂量的抗生素。对于可注射的β-内酰胺，标准和高剂量仅被提议用于短期输注方案.
目的：评估长期输注（PI）和连续输注（CI）的β-内酰胺类药物的剂量。
方法：对7种可注射β-内酰胺：氨曲南，头孢吡肟,头孢噻肟,头孢西丁,头孢他啶,哌拉西林和替莫西林.基于短输注的各种剂量方案，在虚拟患者中模拟PIorCI。根据参照群体PK模型获得药代动力学（PK）谱和PTA，以及EUCAST提出的PK/药效学靶标和MIC断点。与达到断点的推荐剂量相似的PTA值相关的替代剂量方案被认为是可接受的。
结果：大多数EUCAST短剂量给药方案均证实了足够的PTA。基于PI（3至4小时）或CI的总共9个标准剂量和14个高剂量被确定为替代品。头孢吡肟和氨曲南,对于假单胞菌引起的感染，只有PI和CI方案才能达到可接受的PTA。：头孢吡肟的2gq8h为4h的PI或6g/24hCI；氨曲南的2gq6h为3h的PI或6g/24hCI。
结论：这些替代标准和高剂量方案有望提供与新的EUCAST敏感性类别和相关MIC断点定义相容的抗生素暴露。然而,进一步的临床评估是必要的。
目的：评估长期输注（PI）和连续输注（CI）的β-内酰胺类药物的剂量。
方法：对7种可注射β-内酰胺：氨曲南，头孢吡肟,头孢噻肟,头孢西丁,头孢他啶,哌拉西林和替莫西林.基于短输注的各种剂量方案，在虚拟患者中模拟PIorCI。根据参照群体PK模型获得药代动力学（PK）谱和PTA，以及EUCAST提出的PK/药效学靶标和MIC断点。与达到断点的推荐剂量相似的PTA值相关的替代剂量方案被认为是可接受的。
结果：大多数EUCAST短剂量给药方案均证实了足够的PTA。基于PI（3至4小时）或CI的总共9个标准剂量和14个高剂量被确定为替代品。头孢吡肟和氨曲南,对于假单胞菌引起的感染，只有PI和CI方案才能达到可接受的PTA。：头孢吡肟的2gq8h为4h的PI或6g/24hCI；氨曲南的2gq6h为3h的PI或6g/24hCI。
结论：这些替代标准和高剂量方案有望提供与新的EUCAST敏感性类别和相关MIC断点定义相容的抗生素暴露。然而,进一步的临床评估是必要的。
