Antibiotic Dosing in Geriatric Patients At the Emergency Department (AGED)

Ghent University Hospital (UZ)

Status: Enrolling

Conditions: Elderly Infection; Frailty; Frail Elderly Syndrome; Infection, Bacterial

Treatments: Diagnostic Test: Blood sampling; Diagnostic Test: Hemoculture; Diagnostic Test: Sputum sample; Diagnostic Test: Urine sample

Study type: Observational

Funder types: Other

Identifiers

NCT04436991

EC/2017/1369 (BC-01030)

Details and patient eligibility

About

In this pilot study, we will investigate whether - with the current dosing regimens, used in the Ghent University Hospital - pharmacodynamic targets regarding beta-lactam antibiotics (more specific Amoxicilline-Clavulanate, Piperacillin-Tazobactam and Temocillin) are attained in frail patients admitted to the geriatric department.

Full description

In drug research studies, older people - and especially patients with a geriatric profile or frailty risk - are very frequently excluded. Moreover, drug dosing is often extrapolated from studies in younger adults with failure to consider potential differences in pharmacokinetics (PK) and pharmacodynamics (PD).

Studies on dosing of beta-lactam antibiotics in geriatric or frail patients aged 75 years or older have, to the best of our knowledge, never been performed.

In this pilot study, we will investigate whether - with the current dosing regimens, used in the Ghent University Hospital - pharmacodynamic targets regarding beta-lactam antibiotics (more specific Amoxicilline-Clavulanate, Piperacillin-Tazobactam and Temocillin) are attained in frail patients admitted to the geriatric department.

This monocentric, prospective, observational trial is currently ongoing at the emergency department and geriatric department of the Ghent University Hospital.

Amoxicillin/clavulanic acid 1000/200mg of piperacillin-tazobactam 4000mg or temocillin 2000mg was infused intravenously over 30 minutes using a syringe pump. The standard dosing regimes were used.

An infusion catheter of minimum 18-gauge was placed in the contralateral arm to the arm in which the antibiotic dose was administered. Blood samples were collected from this catheter at first dose and assumed steady state conditions. Steady state was assumed to be reached after minimal 24h (> 4 doses at four - six hourly interval) of therapy. The goal was to obtain 5 first dose and 5 steady dose samples in every patient.

Material for bacteriological analysis, such as blood cultures, urine samples, sputum, were collected in every patient according to standard care. In case of bacterial growth, MIC's were measured on the reported strains when possible.

Amoxicillin, clavulanic acid, piperacillin, tazobactam and temocillin were measured using a validated ultra-performance liquid chromatographic method with tandem mass spectrometric detection.

Serum creatinine, cystatin C, procalcitonin, infection parameters (CRP, WBC count) and albumin were obtained from standard blood samples performed in these patients at day one and also later on during their therapy.

Three frailty score systems (KATZ, Geriatric 8 - G8, Cumulative Illness Rating Scale - CIRS) were calculated.

Enrollment: 180 estimated patients

Sex: All

Ages: 75+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients presenting at the emergency department and later on admitted to the geriatric department
• Patient age 75 years or older
• Patients with geriatric profile according to KATZ scale, G8 screening test or CIRS score.
• Patient receiving antibiotic treatment (amoxicillin-clavulanate, piperacillin-tazobactam)
• Intravenous access available for blood sampling. For measurement of the peak concentration an intravenous access other than the drug infusion line is required.

Exclusion criteria

• Admission to other units than the geriatric department incl. the ICU.
• Absence of informed consent
• Known hypersensitivity to beta-lactam antibiotics
• Patients who received oral amoxicillin-clavulanate prior to admission will not be included in the iv. amoxicillin-clavulanate group.

Trial design

180 participants in 3 patient groups

Amoxicillin-clavulanate

Description:

Administration of amoxicillin-clavulanate as standard care therapy (4x or 6x 1g/d). Blood sampling in early and steady state dose (up to 5 samplings per dose). Collection of hemocultures, urine samples and sputum samples when possible.

Treatment:

Diagnostic Test: Urine sample

Diagnostic Test: Sputum sample

Diagnostic Test: Hemoculture

Diagnostic Test: Blood sampling

Piperacillin-tazobactam

Description:

Administration of piperacillin-tazobactam as standard care therapy (4x 4g/d). Blood sampling in early and steady state dose (up to 5 samplings per dose). Collection of hemocultures, urine samples and sputum samples when possible.

Treatment:

Diagnostic Test: Urine sample

Diagnostic Test: Sputum sample

Diagnostic Test: Hemoculture

Diagnostic Test: Blood sampling

Temocillin

Description:

Administration of temocillin as standard care therapy (2x or 3x 2g/d). Blood sampling in early and steady state dose (up to 5 samplings per dose). Collection of hemocultures, urine samples and sputum samples when possible.

Treatment:

Diagnostic Test: Urine sample

Diagnostic Test: Sputum sample

Diagnostic Test: Hemoculture

Diagnostic Test: Blood sampling