The OPTIMAL TDM Study: Determining Optimal Beta-lactam Plasma Concentrations Through Therapeutic Drug Monitoring

University of Geneva, Switzerland

Status: Completed

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

Treatments: Other: The study is observational.

Study type: Observational

Funder types: Other

Identifiers

NCT03790631

2018-01830

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 771 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Hospitalized patients with suspected or confirmed systemic bacterial infection:

1. Receiving either imipenem-cilastatin, meropenem, amoxicillin (±clavulanic acid), flucloxacillin, piperacillin-tazobactam, ceftazidime or cefepime
2. Aged ≥18 years
3. Requiring intensive or intermediate-intensive (step-down) care OR severely immunosuppressed (see definitions)

Exclusion criteria

1. Planned imminent transfer to an outside hospital
2. Poor prognosis with life expectancy <1 week and/or intended transition to palliative care

Trial design

771 participants in 7 patient groups

imipenem TDM

Description:

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.

Treatment:

Other: The study is observational.

meropenem TDM

Description:

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

Treatment:

Other: The study is observational.

piperacillin TDM

Description:

Adult patients receiving piperacillin (with or without tazobactam) for suspected or confirmed bacterial infection. TDM will be performed to assess intermediate and trough levels once the patient is at steady-state.

Treatment:

Other: The study is observational.

flucloxacillin TDM

Description:

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

Treatment:

Other: The study is observational.

amoxicillin TDM

Description:

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

Treatment:

Other: The study is observational.

ceftazidime TDM

Description:

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

Treatment:

Other: The study is observational.

cefepime TDM

Description:

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

Treatment:

Other: The study is observational.