Brief Summary

Little is known of beta-lactam antibiotics' true therapeutic plasma concentration range. The aims of this study are to define evidence-based, safe and effective upper and lower limits of the plasma concentrations of imipenem, meropenem, amoxicillin, flucloxacillin, piperacillin, ceftazidime and cefepime in patients at increased risk of serious bacterial infections and currently understudied pharmacokinetics (the critically ill, the elderly, and the immunosuppressed). This prospective observational study will include adult patients with suspected or confirmed systemic bacterial infection receiving one of the above-named antibiotics and hospitalized in intensive-care, step-down, or hematology-oncology units of the Geneva University Hospitals (HUG). Eligible patients will be identified via the electronic health record (EHR). Patients receiving traditional intermittent dosing or prolonged infusions will undergo TDM for at least one intermediate (mid-interval) and one trough level at 24 hours (-12 or +48 hours) after the therapy's start. Patients receiving continuous infusions will undergo TDM for at least one steady-state level. Clinical course will be observed for 30 days from the start of the study antibiotic (1st day of study antibiotic =day 1). The primary outcome is incidence of clinical toxicity through day 30 after start of study antibiotic (as stratified by BL trough concentration). Secondary outcomes are listed below.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

771

participants targeted

Target at P75+ for all trials

Timeline

Completed

Started Jan 2019

Longer than P75 for all trials

Geographic Reach

1 country

1 active site

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

5 years study duration

First Submitted

Initial submission to the registry

December 27, 2018

Completed

4 days until next milestone

First Posted

Study publicly available on registry

December 31, 2018

Completed

14 days until next milestone

Study Start

First participant enrolled

January 14, 2019

Completed

5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2023

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2023

Completed

Last Updated

May 20, 2025

Status Verified

May 1, 2025

Enrollment Period

5 years

First QC Date

December 27, 2018

Last Update Submit

May 14, 2025

Conditions

Beta-lactam Antibiotics Therapeutic Drug Monitoring Toxicity Efficacy Imipenem Meropenem Piperacillin Flucloxacillin Amoxicillin Ceftazidime Cefepime

Outcome Measures

Primary Outcomes (1)

Incidence of clinical toxicity through day 30 after start of study antibiotic
Incidence of clinical toxicity through day 30 after start of study antibiotic (as stratified by BL trough concentration)
day 30 after start of antibiotic

Secondary Outcomes (13)

Clinical response: incidence of clinical cure
day 30
clinical response in patients with neutropenic fever: incidence of clinical cure in this subpopulation
day 30
30-day mortality attributable to the treated infection
day 30
30-day all-cause mortality
day 30
incidence of reversible toxicity
day 30
+8 more secondary outcomes

Study Arms (7)

imipenem TDM

Adult patients receiving imipenem for suspected or confirmed bacterial infection. TDM will be performed to assess intermediate and trough levels once the patient is at steady-state.