SUMMARY Rationale: Optimal antibiotic dosing in patients with bacterial infections is of high
importance. Underdosing can lead to treatment failure and can promote emergence of
antimicrobial resistance, while overdosing may lead to (harmful) side effects. The antibiotic
cefuroxime is a second-generation cephalosporin and is frequently used in hospitalized
patients. Cefuroxime exhibits, like other cephalosporins, time-dependent killing. 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%T>MIC is associated with antimicrobial therapeutic efficacy of cefuroxime.
Because cefuroxime is almost exclusively excreted through the kidneys, dose reduction of
cefuroxime for patients with renal impairment (eGFR<30ml/min/1.73m2) is standard of care. No
prospective evidence exists that currently guideline-recommended cefuroxime 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 cefuroxime.
Objective: To investigate whether the PK-PD target of cefuroxime (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 cefuroxime. Study design:
Observational, prospective single center cohort study Study population: Adult patients (age ≥
18 years) on general wards of Noordwest Ziekenhuisgroep (NWZ) receiving cefuroxime as part of
standard care.
Intervention: Three venapunctures within a period of 72 hours, containing a maximum of 18ml
of venous blood in total.
Main study parameters: Percentage of patients attaining the cefuroxime PK-PD target of
50%T>MIC. This will be investigated for patients with adequate renal function receiving a
regular cefuroxime dose and impaired renal function receiving a guideline recommended reduced
dose.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness: 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 cefuroxime treatment is part of standard
care, but the group related benefit could be significant. With the results of this study,
current recommended cefuroxime dosing regimens are prospectively validated or an advice to
reconsider current guidelines will be obtained.