Betalactam Pharmacokinetics in Endocarditis Patients

Objectives The primary objective of the study is to determine the pharmacokinetics of beta-lactam antibiotics in patients with infectious endocarditis, and how the pharmacokinetic profile is associated with various patient factors (e.g. age, body weight, renal function). Secondary objectives are to descriptively assess potential associations between drug exposure, pharmacokinetic/pharmacodynamic targets and clinical outcomes.

Inclusion of patients and sample size Patients are prospectively included at the departments of infectious diseases, internal and acute medicine, cardiology and thoracic surgery at four University Hospitals in Sweden; Uppsala University Hospital, Sahlgrenska University Hospital in Gothenburg, Skåne University Hospital in Lund and Karolinska University Hospital in Stockholm. Potential participants are screened for using the electronic medical records. Inclusion criteria are as follows: (1) admission at one of the study wards, (2) a diagnosis of probable or verified infectious endocarditis, (3) treatment with ampicillin, penicillin G, cefotaxime or cloxacillin and (4) informed written consent to participate in the study. The following exclusion criteria will be applied: (1) age less than 18 years and (2) ongoing or planned hemodialysis.

Based on previous research using similar methods, 30 patients per antibiotic substance (total 150 patients) is considered sufficient to develop a robust mathematical model.

Collection of blood samples and patient data Following inclusion, a series of samples will be taken within one week from start of treatment. Beta-lactams are normally prescribed at 6-8 h dose intervals. One series of 6 blood samples will be collected at 0, 0,5, 1, 2, 4 and 6 or 8 h (depending on dose interval, prior to next dose) after administration of antibiotics. Thereafter, samples will be collected once weekly and 0, 3 or 4 (mid-dose interval) and 6 or 8 h (depending on dose interval, prior to next dose).

Information on patient characteristics, including age, body weight, and gender, will be obtained from the electronic medical records. Further, the results of biomarkers (e.g. albumin, creatinine, CRP), collected as part of routine practice, will be noted. If not collected as standard of care, patients will be subject to extra samples to ensure biomarkers are monitored at least twice weekly.