Target attainment and population pharmacokinetics of flucloxacillin in critically ill patients: a multicenter study.

PURPOSE: Insufficient antimicrobial exposure has been associated with worse clinical outcomes. Reportedly, flucloxacillin target attainment in critically ill patients was heterogeneous considering the study population selection and reported target attainment percentages. Therefore, we assessed flucloxacillin population pharmacokinetics (PK) and target attainment in critically ill patients. METHODS: This prospective, multicenter, observational study was conducted from May 2017 to October 2019 and included adult, critically ill patients administered flucloxacillin intravenously. Patients with renal replacement therapy or liver cirrhosis were excluded. We developed and qualified an integrated PK model for total and unbound serum flucloxacillin concentrations. Monte Carlo dosing simulations were performed to assess target attainment. The unbound target serum concentration was four times the minimum inhibitory concentration (MIC) for ≥ 50% of the dosing interval (ƒT>4xMIC ≥ 50%). RESULTS: We analyzed 163 blood samples from 31 patients. A one-compartment model with linear plasma protein binding was selected as most appropriate. Dosing simulations revealed 26% ƒT>2 mg/L ≥ 50% following continuous infusion of 12 g flucloxacillin and 51% ƒT>2 mg/L ≥ 50% for 24 g. CONCLUSION: Based on our dosing simulations, standard flucloxacillin daily doses of up to 12 g may substantially enhance the risk of underdosing in critically ill patients. Prospective validation of these model predictions is needed.

Clinical effectiveness of flucloxacillin delivery using an elastomeric device for outpatient parenteral antimicrobial therapy.

There has been a surging interest in using elastomeric infusion devices to deliver outpatient parenteral antimicrobial therapy (OPAT), which is more cost-effective than standard antibiotic administration, which requires multiple daily home visits. This has been particularly important since the outbreak of the coronavirus pandemic, because reducing patient contact can also help to minimise transmission of COVID-19 to outpatients who are at a high risk of COVID-19-triggered complications. In this retrospective study, the clinical effectiveness of intravenous (IV) infusion of flucloxacillin using an elastomeric device was explored in a convenience sample of patients. Patients with three primary infective diagnoses-bloodstream infection, non-vertebral osteomyelitis and vertebral osteomyelitis-were included in the analyses. In non-vertebral osteomyelitis patients, Accufuser antibiotic infusion shortened the course of OPAT care relative to standard antibiotic administration (p<.05). In contrast, in vertebral osteomyelitis patients, it prolonged the course of OPAT care relative to standard administration (p<.05). In patients with bloodstream infections, no significant difference was found between the treatment modes (p=.93). Thus, the clinical effectiveness of Accufuser antibiotic infusion varies among patients with different infective diagnoses, and there seems to be a complex relationship between the method of antibiotic delivery and the patient's condition.