Influencing Factors of Vancomycin Trough Level in Critically Ill Children With Sepsis

NCT ID: NCT06661772

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 160 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2024-10-20

Brief Summary

The aim of the work will be to measure the vancomycin trough concentration in critically ill children with sepsis in pediatric intensive care unit and its influencing factors.

Detailed Description

Timely antibiotic administration and optimal drug dosing are crucial to achieving therapeutic antibiotic levels in critically-ill pediatric patients with suspected bacterial infection. However, drug elimination through renal excretion is often enhanced in critically ill patients . This phenomenon, referred to as augmented renal clearance (ARC), may cause sub-therapeutic serum concentrations of antibiotics through enhanced glomerular filtration, resulting in treatment failure and the generation of antibiotic-resistant strains.

Vancomycin is a tricyclic glycopeptide antibiotic with broad spectrum activity against gram-positive bacteria. It is effective for the treatment of gram positive infections and is the drug of choice for methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin is poorly absorbed following oral administration. Therefore, it is commonly administered as an intravenous infusion. Approximately 50% of vancomycin is protein bound in plasma with a variable volume of distribution. An initial distribution half-life ranging from 30 min to 1 h followed by a mean terminal elimination half-life ranging from 6 h to 12 h was determined following intravenous dosing in patients with normal renal function. Metabolism is negligible and elimination occurs primarily through glomerular filtration, such that advanced renal disease substantially reduces the clearance of vancomycin resulting in an elimination half-life of about 7.5 days compared to 4-6 h in normal patients. This means that in patients with kidney failure, the dosing of vancomycin must be adjusted.

Standard treatment guidelines recommend maintaining trough levels of vancomycin between 10 and 20 mg/L. The recommended trough levels are likely to ensure optimum bactericidal activity of vancomycin, based on the minimum inhibitory concentrations (MICs) for MRSA (the lowest concentration of the drug that can prevent growth of visible bacteria).

Studies have reported a threefold increase in the risk of worsening of infections if the MICs for MRSA exceed 1.5 mg/L. However, guidelines suggest maintaining a minimum trough level of 10 mg/L for vancomycin. On the other hand, higher trough levels of vancomycin increase the risk of nephrotoxicity by two times.

Investigators have reported a correlation between serum antibiotic concentration and glomerular filtration rate (GFR). The measured GFR (mGFR), based on urine creatinine clearance over a 24-hour period, is widely used to identify patients with ARC. However, prompt administration of the proper antibiotic dose enables the serum concentration to reach therapeutic levels quickly, and the 24-hour delay when using the mGFR to identify ARC may have an adverse effect on treatment outcome in critically-ill children.

Measured glomerular filtration rate (mGFR) is often used to identify augmented renal clearance (ARC). However, in the clinical setting, estimated GFR (eGFR) is obtained more quickly and inexpensively. Therefore, eGFR can be used to identify ARC by evaluating the correlation between the eGFR and vancomycin trough level (VTL).

At our institution, empirical vancomycin therapy is commonly used due to the elevated incidence of community-acquired methicillin-resistant Staphylococcus aureus infections in the PICU. Dose adjustments based on renal function are needed, necessitating vancomycin therapeutic drug monitoring. Comparing critically ill children with sepsis to patients with normal or decreased eGFR, we hypothesize that subtherapeutic VTL has been associated with ARC.

Conditions

Critically Ill Children; Sepsis

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

All pediatric Patients less than 16 years old who were diagnosed with sepsis & admitted to PICU

All consecutively hospitalized children (less than 16 years old) admitted to 30 beds in PICU who were treated with the first course of vancomycin as empirical therapy for suspected sepsis without AKI by the time of the start of treatment were enrolled in the study.

Vancomycin trough concentration method

Intervention Type: DIAGNOSTIC_TEST

A blood sample for VTL was drawn 30 minutes before administration, prior to the fourth dose of vancomycin, under a complete aseptic technique, unless otherwise ordered by the medical team. Vancomycin serum concentrations were measured using a Human vancomycin ELISA Kit.

Interventions

Vancomycin trough concentration method

A blood sample for VTL was drawn 30 minutes before administration, prior to the fourth dose of vancomycin, under a complete aseptic technique, unless otherwise ordered by the medical team. Vancomycin serum concentrations were measured using a Human vancomycin ELISA Kit.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• All consecutively hospitalized children (less than 16 years old), who admitted to 30 beds in PICU who were treated with the first course of vancomycin as empirical therapy for suspected sepsis without AKI by the time of the start of treatment were enrolled in the study.

Exclusion Criteria

• children who commenced vancomycin for preventive measures, those with a history of multiple vancomycin treatment cycles, individuals showing signs of renal impairment upon initial admission to the PICU based on the pediatric risk, injury, failure, loss, end-stage renal disease (pRIFLE) criterion, and those diagnosed with congenital muscle disorders due to the potential influence of their underlying condition on serum creatinine levels.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Benha University

OTHER

Sponsor Role: lead

Responsible Party

Amany Mohammed El-Rebigi, MD

Lecturer of pediatric

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Benha University

Cairo, Al-Qalyubia, Egypt

Countries

Egypt

Other Identifiers

Rc 19-5-2024

Identifier Type: -

Identifier Source: org_study_id