Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial

Tospon Lertwattanachai; Preecha Montakantikul; Viratch Tangsujaritvijit; Pitsucha Sanguanwit; Jetjamnong Sueajai; Saranya Auparakkitanon; Pitchaya Dilokpattanamongkol

doi:10.1186/s40560-020-00442-7

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial

J Intensive Care. 2020 Apr 15:8:26. doi: 10.1186/s40560-020-00442-7. eCollection 2020.

Authors

Tospon Lertwattanachai¹, Preecha Montakantikul¹, Viratch Tangsujaritvijit^{2

3}, Pitsucha Sanguanwit⁴, Jetjamnong Sueajai⁵, Saranya Auparakkitanon⁵, Pitchaya Dilokpattanamongkol¹

Affiliations

¹ 1Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, 10400 Thailand.
² 2Department of Critical Care Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
³ Piyavate Hospital, Bangkok, Thailand.
⁴ 4Department of Emergency Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
⁵ 5Toxicology Laboratory, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Abstract

Background: 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.

Methods: 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.

Results: 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; P 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); P 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); P value = 0.045) or on mechanical ventilator (87.5% (7/8) vs. 23.1% (3/13); P value = 0.008) than the standard-dose group. Adverse events were comparable between the two groups.

Conclusions: 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.

Trial registration: ClinicalTrials.gov, NCT03344627, registered on November 17, 2017.

Keywords: Clinical outcome; Empirical therapy; High dose; Meropenem; Sepsis; Septic shock.

Associated data

ClinicalTrials.gov/NCT03344627