No advantage of continuous vs intermittent meropenem in critically ill patients – the MERCY trial

1. The MERCY trial revealed that continuous infusion of meropenem does not confer a significant advantage over intermittent administration in reducing mortality and preventing new antibiotic-resistant bacteria in patients with either septic shock or sepsis.

2. This randomized control trial provides contrary evidence to previous systematic reviews and meta-analyses that found better outcomes with continuous meropenem.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Meropenem, a widely used β-lactam antibiotic, has traditionally been administered intermittently to treat infections in critically ill patients. However, recent studies have suggested that continuous administration might offer advantages such as enhanced bacterial clearance, reduced growth of antibiotic-resistant bacteria, and decreased mortality. In light of this, a randomized clinical trial called the Continuous Infusion vs Intermittent Administration of Meropenem in Critically Ill Patients (MERCY) was conducted to assess the occurrence of new antimicrobial resistance and mortality between the two administration methods. The study findings revealed that continuous administration did not significantly reduce the composite outcome of all-cause mortality and the emergence of pan-drug-resistant or extensively drug-resistant bacteria by day 28. A limitation of the study was that clinicians were permitted to adjust the meropenem dosage during the study period based on kidney function or clinical judgment, although guidance on dosage was provided. In conclusion, the MERCY trial provides valuable insights into the administration methods of meropenem in critically ill patients. Further research may be warranted to explore alternative administration strategies to mitigate antibiotic resistance.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Clinical outcomes of continuous vs intermittent meropenem infusion for the treatment of sepsis  

In-Depth [randomized clinical trial]: This study was a double-blind, randomized clinical trial conducted between June 2018 and November 2022. It involved critically ill adult patients with sepsis or septic shock who were prescribed meropenem. Exclusion criteria included previous therapy with carbapenem antibiotics, a very low probability of survival using the Simplified Acute Physiology Score (SAPS II), and severe immunosuppression. A total of 607 patients were recruited from 31 intensive care units in Croatia, Italy, Kazakhstan, and Russia. The median duration of meropenem administration was 11 days (IQR, 6-17 days), and overall median doses were 24 g (continuous) and 21 g (intermittent). The rates of all-cause mortality and the emergence of antibiotic-resistant bacteria were similar between the continuous administration group (47%) and the intermittent administration group (49%). The relative risk was not statistically significant, calculated at 0.96 (95% confidence interval, 0.81-1.13, p=0.60). Prespecified subgroup, modified intention-to-treat and per-protocol analyses showed no significant between-group differences. Additionally, none of the secondary outcomes exhibited statistical significance, including 90-day mortality and the number of days alive and free from ICU or antibiotics by day 28. No adverse events, such as seizures or allergic reactions, were recorded during the trial.

Image: PD

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