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Published on: August 30, 2018
Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized
Giacomo Monti1,2, Nikola Bradic3,4, Matteo Marzaroli1
1Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Importance:
Meropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes.
Objective:
To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis.
Design, Setting, And Participants:
A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022.
Interventions:
Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304).
Main Outcomes And Measures:
The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events.
Results:
All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients).
Conclusions And Relevance:
In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03452839.
Insights
Continuous meropenem infusion did not improve outcomes in critically ill sepsis patients. This antibiotic administration method did not reduce mortality or the emergence of drug-resistant bacteria compared to intermittent dosing.
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Pharmacodynamics
Background:
- Meropenem, a broad-spectrum beta-lactam antibiotic, is crucial for treating severe infections.
- Optimal meropenem efficacy is achieved through continuous infusion, maintaining drug levels above the minimum inhibitory concentration.
- Continuous infusion may offer clinical advantages over intermittent dosing in critically ill patients.
Purpose of the Study:
- To compare the efficacy of continuous versus intermittent meropenem administration in critically ill sepsis patients.
- To assess the impact on a composite outcome of mortality and the emergence of pandrug-resistant or extensively drug-resistant bacteria.
- To evaluate secondary outcomes including days alive and free from antibiotics or intensive care.
Main Methods:
- A double-blind, randomized clinical trial involving 607 critically ill patients with sepsis or septic shock across 4 countries.
- Patients received meropenem via either continuous infusion (n=303) or intermittent administration (n=304).
- The primary outcome was a composite of all-cause mortality and emergence of drug-resistant bacteria at day 28.
Main Results:
- The primary composite outcome occurred in 47% of the continuous group and 49% of the intermittent group (RR, 0.96; P=.60), showing no significant difference.
- No statistically significant differences were observed in any of the four secondary outcomes.
- Mortality at 90 days was 42% in both the continuous and intermittent administration groups.
Conclusions:
- Continuous meropenem administration did not demonstrate superiority over intermittent dosing in reducing mortality or the emergence of drug-resistant bacteria in critically ill sepsis patients.
- The findings suggest that current intermittent dosing strategies remain a viable option for meropenem administration in this patient population.
- Further research may be needed to identify specific patient subgroups who might benefit from continuous meropenem infusion.
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