To investigate whether the PK-PD target of ceftazidime (50%T>MIC) is attained in the first 24 hours of treatment in adult patients on general wards with adequate and impaired renal function receiving regular and reduced doses of ceftazidime.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage of patients attaining the ceftazidime PK-PD target of 50%T>MIC. This
will be investigated for patients with adequate renal function receiving a
regular ceftazidime dose and impaired renal function receiving a guideline
recommended reduced dose.
Secondary outcome
To investigate whether the current dosing regimen of ceftazidime, recommended
by the SWAB guideline and applied at Amsterdam UMC, location AMC for adult
patients with various degrees of renal function on general wards, results in
PK-PD target attainment of 50%T>MIC after 24-48 hours of therapy.
To investigate whether the current dosing regimen of ceftazidime, recommended
by the SWAB guideline and applied at Amsterdam UMC, location AMC for adult
patients with various degrees of renal function on general wards, results in
PK-PD target attainment of 100%T>MIC during the first 24 hours of therapy.
To compare ceftazidime exposure at 24 hours and 24-48 hours after start of
treatment between three different renal function groups in terms of AUC and
Cmin. (Group A: eGFR *50ml/min/1.73m2 treated with standard doses of
ceftazidime, Group B: eGFR 49-30ml/min/1.73m2 treated with reduced doses of
ceftazidime and Group C: eGFR 29-10 ml/min/1.73m2 treated with reduced doses of
ceftazidime).
If a large proportion, defined as a percentage of 25% or a minimum of 10
patients, does not attain the primary objective (50%T>MIC), we will explore
whether or not attaining this target is associated with patients* clinical
outcome, in terms of:
length of hospital stay (LOS), since start of ceftazidime treatment, admission
to and duration of ICU stay after start of ceftazidime treatment, 30 days
mortality after start of ceftazidime treatment, antibiotic switch to
carbapenems (meropenem, imipenem or ertapenem) within 30 days after start of
treatment with ceftazidime and days of fever after start of treatment with
ceftazidime
Background summary
The pharmacodynamic target can therefore be best described as the percentage of
the dosing interval that the serum concentration remains above the minimum
inhibitory concentration (MIC) of the bacteria (T>MIC). Attaining the
pharmacokinetic-pharmacodynamic (PK-PD) target of 50%TMIC is associated with
antimicrobial therapeutic efficacy of ceftazidime.
Because ceftazidime is almost exclusively excreted through the kidneys, dose
reduction of ceftazidime for patients with renal impairment
(eGFR<50ml/min/1.73m2) is standard of care. No prospective evidence exists that
currently guideline-recommended ceftazidime dosing regimens result in at least
50%T>MIC in adult patients on general wards, especially not in patients with
renal impairment receiving a reduced dose of ceftazidime.
Study objective
To investigate whether the PK-PD target of ceftazidime (50%T>MIC) is attained
in the first 24 hours of treatment in adult patients on general wards with
adequate and impaired renal function receiving regular and reduced doses of
ceftazidime.
Study design
Observational, prospective multi center cohort study
Study burden and risks
Risks imposed by participation are considered negligible. Three venapunctures,
obtaining a maximum of 18 ml venous blood are not expected to cause AEs or
SAEs. Participation itself does not bring any benefit as ceftazidime treatment
is part of standard care, but the group related benefit could be significant.
With the results of this study, current recommended ceftazidime dosing regimens
are prospectively validated or an advice to reconsider current guidelines will
be obtained.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Receiving ceftazidime therapy intravenous (iv) as part of standard care
Age * 18 years
Admitted to a general ward of Amsterdam UMC - location AMC or Noordwest
Ziekenhuisgroep location Alkmaar
Informed consent is obtained
Exclusion criteria
Mentally incapacitated patients , i.e. a minor or legally incompetent adult
Renal replacement therapy during treatment with ceftazidime
Patients admitted to the intensive care unit (ICU)
Severely burned patients, defined as a burned surface * 10%
Patients with cystic fibrosis
Informed consent is not obtained
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL70808.018.19 |