Lertwattanachai Tospon, Montakantikul Preecha, Tangsujaritvijit Viratch, Sanguanwit Pitsucha, Sueajai Jetjamnong, Auparakkitanon Saranya, Dilokpattanamongkol Pitchaya
1Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, 10400 Thailand.
2Department of Critical Care Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
J Intensive Care. 2020 Apr 15;8:26. doi: 10.1186/s40560-020-00442-7. eCollection 2020.
Appropriate antimicrobial dosing is challenging because of changes in pharmacokinetics (PK) parameters and an increase in multidrug-resistant (MDR) organisms in critically ill patients. This study aimed to evaluate the effects of an empirical therapy of high-dose versus standard-dose meropenem in sepsis and septic shock patients.
We performed a prospective randomized open-label study to compare the changes of modified sequential organ failure assessment (mSOFA) score and other clinical outcomes of the high-dose meropenem (2-g infusion over 3 h every 8 h) versus the standard-dose meropenem (1-g infusion over 3 h every 8 h) in sepsis and septic shock patients. Patients' characteristics, clinical and microbiological outcomes, 14 and 28-day mortality, vasopressor- and ventilator-free days, intensive care unit (ICU) and hospital-free days, percent of the time of antibiotic concentrations above the minimum inhibitory concentration (%T>MIC), and safety were assessed.
Seventy-eight patients were enrolled. Median delta mSOFA was comparable between two groups (- 1 in the high-dose group vs. - 1 in the standard-dose group; value = 0.75). There was no difference between the two groups regarding clinical and microbiological cure, 14- and 28-day mortality, vasopressor- and ventilator-free days, and ICU- and hospital-free days. In patients admitted from the emergency department (ED) with a mSOFA score ≥ 7, the high-dose group demonstrated significantly better microbiological cure compared with the standard-dose group (75% (9/12 patients) vs. 20% (2/10 patients); value = 0.03). Likewise, the high-dose group presented higher microbiological cure rate in patients admitted from ED who had either APACHE II score > 20 (83.3% (10/12) vs. 28.6% (2/7); value = 0.045) or on mechanical ventilator (87.5% (7/8) vs. 23.1% (3/13); value = 0.008) than the standard-dose group. Adverse events were comparable between the two groups.
Empirical therapy with the high-dose meropenem presented comparable clinical outcomes to the standard-dose meropenem in sepsis and septic shock patients. Besides, subgroup analysis manifested superior microbiological cure rate in sepsis or septic shock patients admitted from ED.
ClinicalTrials.gov, NCT03344627, registered on November 17, 2017.
由于重症患者的药代动力学（PK）参数发生变化以及多重耐药（MDR）菌增加，合理的抗菌药物剂量选择具有挑战性。本研究旨在评估高剂量与标准剂量美罗培南经验性治疗对脓毒症和脓毒性休克患者的影响。
我们进行了一项前瞻性随机开放标签研究，以比较高剂量美罗培南（每8小时3小时输注2克）与标准剂量美罗培南（每8小时3小时输注1克）在脓毒症和脓毒性休克患者中的改良序贯器官衰竭评估（mSOFA）评分变化及其他临床结局。评估了患者的特征、临床和微生物学结局、14天和28天死亡率、无血管活性药物和无呼吸机天数、重症监护病房（ICU）和非住院天数、抗生素浓度高于最低抑菌浓度的时间百分比（%T>MIC）以及安全性。
共纳入78例患者。两组的mSOFA中位数变化相当（高剂量组为-1，标准剂量组为-1；P值=0.75）。两组在临床和微生物学治愈、14天和28天死亡率、无血管活性药物和无呼吸机天数以及ICU和非住院天数方面无差异。在急诊室（ED）入院且mSOFA评分≥7的患者中，高剂量组的微生物学治愈率显著高于标准剂量组（75%（9/12例患者）对20%（2/10例患者）；P值=0.03）。同样，在APACHE II评分>20（83.3%（10/12）对28.6%（2/7）；P值=0.045）或接受机械通气（87.5%（7/8）对23.1%（3/13）；P值=0.008）的ED入院患者中，高剂量组的微生物学治愈率高于标准剂量组。两组的不良事件相当。
在脓毒症和脓毒性休克患者中，高剂量美罗培南的经验性治疗与标准剂量美罗培南的临床结局相当。此外，亚组分析表明，ED入院的脓毒症或脓毒性休克患者的微生物学治愈率更高。
ClinicalTrials.gov，NCT03344627，于2017年11月17日注册。
