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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Meropenem 1 g | Experimental |
| |
| Meropenem 2 g | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Italiano de Buenos Aires | Buenos Aires | Argentina |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34403127 | Background | 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. | |
| 28485312 |
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| 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. |
| 23074313 | 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. |
| 31925610 | 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. |
| 15536528 | 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. |
| ID | Term |
|---|---|
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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