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

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.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

© The Author(s) 2020.

Figures

Fig. 1
Fig. 1
Flow of patients through the trial
Fig. 2
Fig. 2
Bacterial isolates. GN, gram-negative bacteria; MIC, minimum inhibitory concentration
Fig. 3
Fig. 3
Comparison of microbiological cure rate in patients who admitted from the emergency department. ED, emergency department; mSOFA, modified sequential organ failure assessment score; APACHE II, Acute Physiology and Chronic Health Evaluation II; MV, mechanical ventilation

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Source: PubMed

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