Clinical trial NCT04436991: Antibiotic Dosing in Geriatric Patients At the Emergency Department
Official title: Antibiotic Dosing in Geriatric Patients At the Emergency Department
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Elderly Infection
Frailty
Frail Elderly Syndrome
Infection, Bacterial
Keywords: amoxicillin
piperacillin-tazobactam
temocillin
pharmacokinetics
pharmacodynamics
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2020-06-18
Enrollment: 180
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Frail elderly patients with a minimum of 75 years old, presenting at the emergency department and in need for hospitalization at the geriatric ward, in which a betalactam antibiotic treatment was started.

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Blood concentrations of amoxicillin-clavulanate.
timeFrame: Within the first 12 hours (early dose) of treatment and after 24 - 48 hours of treatment (steady state)
measure: Blood concentrations of piperacillin-tazobactam.
timeFrame: Within the first 12 hours (early dose) of treatment and after 24 - 48 hours of treatment (steady state)
measure: Blood concentrations of temocillin.
timeFrame: Within the first 12 hours (early dose) of treatment and after 24 - 48 hours of treatment (steady state)
Secondary outcomes:
measure: Measured total and unbound concentrations of beta-lactam antibiotics.
timeFrame: Within the first 12 hours (early dose) of treatment and after 24 - 48 hours of treatment (steady state)
measure: Response to antimicrobial therapy.
timeFrame: The end of individual antibiotic therapy with an average of 1 week
measure: Achievement of pharmacodynamic targets measured by questionnaire, vital signs, blood results and side effects.
timeFrame: The end of individual antibiotic therapy with an average of 1 week
measure: Clearance of betalactam antibiotics.
timeFrame: Within the first 12 hours (early dose) of treatment and after 24 - 48 hours of treatment (steady state)
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: University Hospital Ghent
Study officials:
affiliation: University Hospital, Ghent
name: Tania Desmet, Dr.
role: PRINCIPAL_INVESTIGATOR
References: