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