Empirical Meropenem Dosing in Critically Ill Patients: Early Assessment of Plasma Exposure and Minimum Inhibitory Concentration Targets

NCT07681544 | Completed

• 1 other identifier: 7038
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this prospective cohort study is to characterize meropenem exposure in critically ill adult patients receiving empiric antibiotic treatment in the intensive care unit (ICU). Empiric treatment refers to the administration of antibiotics before the causative microorganism and its antimicrobial susceptibility profile are known. In clinical practice, meropenem is commonly administered using different dosing strategies, including 1 g or 2 g doses given as either a 30-minute or a 3-hour infusion. The minimum inhibitory concentration (MIC) is the lowest concentration of an antibiotic required to inhibit bacterial growth and is used as a reference value to evaluate antibiotic exposure. The main questions it aims to answer are: Do meropenem plasma concentrations differ between patients receiving 1 g and those receiving 2 g, administered as either a 30-minute or a 3-hour infusion during the first 48 hours of empirical treatment in critically ill patients? Does the duration of time above the theoretical MIC of 2 mg/L differ between patients receiving meropenem 1 g and those receiving 2 g, administered as either a 30-minute or a 3-hour infusion during the first 48 hours of empirical treatment in critically ill patients? Researchers will compare different meropenem dosing regimens (1 g versus 2 g administered as a 30-minute or a 3-hour infusion) to determine which strategy provides a longer duration of plasma concentrations above the theoretical MIC of 2 mg/L. Participants will: Receive meropenem as part of their standard clinical care. Have blood samples collected during the first 48 hours of treatment to measure meropenem plasma concentrations. Have pharmacokinetic/pharmacodynamic parameters evaluated, including the percentage of time that meropenem concentrations remain above the theoretical target MIC. An exploratory objective of the study is to describe 28-day mortality and intensive care unit length of stay according to meropenem dose group.

Conditions

Empirical Antimicrobial Therapy; Critically Ill; Meropenem; Pharmacokinetics and Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• Percentage of time during the first 48 hours of meropenem therapy that plasma concentrations remain above the theoretical target MIC of 2 mg/L (%T>MIC).

  During the first 48 hours of empirical treatment

Study Arms (2)

Meropenem 1 g

EXPERIMENTAL

Diagnostic Test: Blood extraction

Meropenem 2 g

EXPERIMENTAL

Diagnostic Test: Blood extraction

Interventions

Blood extraction DIAGNOSTIC_TEST

Blood samples of 5 ml were collected within the interdose interval. Sample collection times varied among subjects, ensuring coverage of at least one sample every 30 minutes after administration of 1 g or 2 g of meropenem. After collection, samples were immediately transferred to the laboratory and stored at -80 °C until analysis.

Meropenem 1 g; Meropenem 2 g

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years of age.
• Hospitalization in the Intensive Care Unit (ICU), Intermediate Care Unit (ICU step-down/IMCU), or Coronary Care Unit (CCU).
• Receipt of empiric meropenem therapy for at least 24 hours, regardless of the site of infection.
• Written informed consent provided by the patient or their legally authorized representative prior to study participation.

You may not qualify if:

• History of severe adverse reactions to meropenem.
• Availability of microbiological identification results prior to blood sampling for meropenem concentration measurement.

Sponsors & Collaborators

• Hospital Italiano de Buenos Aires: lead

Study Sites (1)

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina

Location

Related Publications (5)

• O'Jeanson A, Larcher R, Le Souder C, Djebli N, Khier S. Population Pharmacokinetics and Pharmacodynamics of Meropenem in Critically Ill Patients: How to Achieve Best Dosage Regimen According to the Clinical Situation. Eur J Drug Metab Pharmacokinet. 2021 Sep;46(5):695-705. doi: 10.1007/s13318-021-00709-w. Epub 2021 Aug 17.

  PMID: 34403127 BACKGROUND

• Zhao HY, Gu J, Lyu J, Liu D, Wang YT, Liu F, Zhu FX, An YZ. Pharmacokinetic and Pharmacodynamic Efficacies of Continuous versus Intermittent Administration of Meropenem in Patients with Severe Sepsis and Septic Shock: A Prospective Randomized Pilot Study. Chin Med J (Engl). 2017 May 20;130(10):1139-1145. doi: 10.4103/0366-6999.205859.

  PMID: 28485312 BACKGROUND

• Dulhunty JM, Roberts JA, Davis JS, Webb SA, Bellomo R, Gomersall C, Shirwadkar C, Eastwood GM, Myburgh J, Paterson DL, Lipman J. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin Infect Dis. 2013 Jan;56(2):236-44. doi: 10.1093/cid/cis856. Epub 2012 Oct 16.

  PMID: 23074313 BACKGROUND

• Kothekar AT, Divatia JV, Myatra SN, Patil A, Nookala Krishnamurthy M, Maheshwarappa HM, Siddiqui SS, Gurjar M, Biswas S, Gota V. Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria. Ann Intensive Care. 2020 Jan 10;10(1):4. doi: 10.1186/s13613-019-0622-8.

  PMID: 31925610 BACKGROUND

• Mehrotra R, De Gaudio R, Palazzo M. Antibiotic pharmacokinetic and pharmacodynamic considerations in critical illness. Intensive Care Med. 2004 Dec;30(12):2145-56. doi: 10.1007/s00134-004-2428-9. Epub 2004 Nov 5.

  PMID: 15536528 BACKGROUND

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: July 2, 2026
• Study Start: June 26, 2024
• Primary Completion: September 20, 2024
• Study Completion: February 15, 2025
• Last Updated: July 8, 2026

Record last verified: 2026-07

Locations

AR (1)