Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial
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Published on: August 30, 2018
Tospon Lertwattanachai1, Preecha Montakantikul1, Viratch Tangsujaritvijit2,3
11Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, 10400 Thailand.
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.
Insights
High-dose meropenem showed similar clinical outcomes to standard-dose for sepsis patients, but improved microbiological cure rates in specific emergency department subgroups. This study evaluated high-dose versus standard-dose meropenem in critically ill patients.
Area of Science:
- Critical care medicine
- Infectious diseases
- Pharmacology
Background:
- Antimicrobial dosing is complex in critically ill patients due to altered pharmacokinetics and rising multidrug-resistant organisms.
- Sepsis and septic shock management requires optimized antibiotic strategies.
Purpose of the Study:
- To compare the efficacy of high-dose versus standard-dose meropenem in patients with sepsis and septic shock.
- To evaluate clinical outcomes, microbiological cure rates, and safety profiles of different meropenem dosing strategies.
Main Methods:
- Prospective randomized open-label study involving 78 sepsis and septic shock patients.
- Comparison of high-dose (2g every 8h) versus standard-dose (1g every 8h) meropenem, both given as 3-hour infusions.
- Assessment of modified sequential organ failure assessment (mSOFA) scores, clinical and microbiological outcomes, mortality, organ-free days, and safety.
Main Results:
- Overall clinical outcomes, including mSOFA score changes and mortality, were comparable between high-dose and standard-dose meropenem groups.
- High-dose meropenem demonstrated significantly superior microbiological cure rates in specific subgroups: patients from the emergency department (ED) with mSOFA ≥ 7, ED patients with APACHE II > 20, and ED patients on mechanical ventilation.
- Adverse events were similar between the two dosing groups.
Conclusions:
- High-dose meropenem is a viable option for sepsis and septic shock, offering comparable clinical outcomes to standard-dose therapy.
- The enhanced microbiological cure rates in specific high-risk emergency department subgroups suggest a potential benefit of high-dose meropenem in these populations.
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