Target Attainment of Cefuroxim

Pharmacokinetic and Pharmacodynamic Target Attainment of Cefuroxime in Adult Patients on General Wards With Different Degrees of Renal Function: a Prospective Observational Cohort Study

SUMMARY Rationale: Optimal antibiotic dosing in patients with bacterial infections is of high importance. Underdosing can lead to treatment failure and can promote emergence of antimicrobial resistance, while overdosing may lead to (harmful) side effects. The antibiotic cefuroxime is a second-generation cephalosporin and is frequently used in hospitalized patients. Cefuroxime exhibits, like other cephalosporins, time-dependent killing. The pharmacodynamic target can therefore be best described as the percentage of the dosing interval that the serum concentration remains above the minimum inhibitory concentration (MIC) of the bacteria (T>MIC). Attaining the pharmacokinetic-pharmacodynamic (PK-PD) target of 50%T>MIC is associated with antimicrobial therapeutic efficacy of cefuroxime.

Because cefuroxime is almost exclusively excreted through the kidneys, dose reduction of cefuroxime for patients with renal impairment (eGFR<30ml/min/1.73m2) is standard of care. No prospective evidence exists that currently guideline-recommended cefuroxime dosing regimens result in at least 50%T>MIC in adult patients on general wards, especially not in patients with renal impairment receiving a reduced dose of cefuroxime.

Objective: To investigate whether the PK-PD target of cefuroxime (50%T>MIC) is attained in the first 24 hours of treatment in adult patients on general wards with adequate and impaired renal function receiving regular and reduced doses of cefuroxime. Study design: Observational, prospective single center cohort study Study population: Adult patients (age ≥ 18 years) on general wards of Noordwest Ziekenhuisgroep (NWZ) receiving cefuroxime as part of standard care.

Intervention: Three venapunctures within a period of 72 hours, containing a maximum of 18ml of venous blood in total.

Main study parameters: Percentage of patients attaining the cefuroxime PK-PD target of 50%T>MIC. This will be investigated for patients with adequate renal function receiving a regular cefuroxime dose and impaired renal function receiving a guideline recommended reduced dose.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Risks imposed by participation are considered negligible. Three venapunctures, obtaining a maximum of 18 ml venous blood are not expected to cause AEs or SAEs. Participation itself does not bring any benefit as cefuroxime treatment is part of standard care, but the group related benefit could be significant. With the results of this study, current recommended cefuroxime dosing regimens are prospectively validated or an advice to reconsider current guidelines will be obtained.

Study Overview

• Status: Recruiting
• Conditions: Infection, Bacterial; Kinesics
• Intervention / Treatment: Diagnostic test: Venapunction

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Saskia E Zieck, MSc; Phone Number: 0031880857476; Email: se.zieck@nwz.nl
• Study Contact Backup: Name: Ingrid MM van Haelst, PhD; Phone Number: 0031880853571; Email: i.van.haelst@nwz.nl

Study Locations

• Netherlands
  • Noord Holland
    • Alkmaar, Noord Holland, Netherlands, 1815JD
      • Recruiting
      • Noordwest Ziekenhuisgroep
      • Contact: Saskia E Zieck, MSc; Phone Number: 0031880857476; Email: se.zieck@nwz.nl
      • Contact: Ingrid M van Haelst, PhD; Phone Number: +31880853571; Email: i.van.haelst@nwz.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Receiving cefuroxime therapy intravenous (iv) as part of standard care
• Age ≥ 18 years
• Admitted to a general ward of Noordwest Ziekenhuisgroep - location Alkmaar
• Informed consent is obtained

Exclusion Criteria:

• Mentally incapacitated patients, i.e. a minor or legally incompetent adult
• Renal replacement therapy during treatment with cefuroxime
• Patients admitted to the intensive care unit (ICU)
• Severely burned patients, defined as a burned surface ≥ 10%
• Patients with cystic fibrosis
• Informed consent is not obtained

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Adequate renal function; Patients with adequate renal function (egfr>30ml/min) receiving a regular cefuroxime dose	Diagnostic test: Venapunction; Three venapunctures within a period of 72 hours, containing a maximum of 18ml of venous blood in total.
Other: Impaired renal function; Patients with impaired renal function (egfr<30ml/min) receiving a guideline recommended reduced dose	Diagnostic test: Venapunction; Three venapunctures within a period of 72 hours, containing a maximum of 18ml of venous blood in total.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target Attainment	Main study parameter is the percentage of the study population attaining the target of 50%T>MIC within the first 24hrs of treatment. To calculate this endpoint cefuroxime concentrations and MIC-values will be obtained.	0-24hours after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target Attainment	Secondary study parameter is the percentage of the study population attaining the target of 50%T>MIC within the first 48hrs of treatment. To calculate this endpoint cefuroxime concentrations and MIC-values will be obtained.	0-48hours after treatment initiation

Collaborators and Investigators

• Sponsor: Noordwest Ziekenhuisgroep

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2022
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: December 20, 2021
• First Submitted That Met QC Criteria: January 7, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: renal function; infectious disease; cefuroxim; target attainment
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: NL78342.029.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No