Optimized dosing of cloxacillin in Staphylococcus aureus bacteremia (SAB) aiming to reduce mortality and morbidity – a pilot study to establish methods, markers for toxicity and a research network.

To study in a future RCT if therapeutic drug monitoring (TDM) of cloxacillin (CL) in SAB improves mortality and morbidity compared to standard dosing (SD).The pilot aims to; describe a Swedish SAB-population, evaluate if renal function can predict risk of under- or overdosing, establish if symptoms or markers of neuro- or nefrotoxicity can be correlated to CL concentrations, to establish the method of measuring the free fraction of CL in plasma in Linköping and to establish a SAB- network.

Studies on optimal dosing in SAB are scarce.

To what extent the target of 100% fT>MIC is reached by SD and how TDM may affect morbidity and mortality has not been studied systematically. Studies suggest that this target can be hard to reach by SD and that overdosing may lead to neuro- or nefrotoxicity.

In the pilot study, demographic data, CL concentrations, blood cultures and neuro-and nefrotoxicity markers will be obtained from patients ≥ 18 y with SAB in Kalmar, Linköping and Norrköping. Primary outcome: Rate of patient that reach 100% ƒT>MIC.

Secondary outcomes: Target attainment in relation to renal function, neuro- and nefrotoxicity in relation to CL exposure, hospital stay (days), mortality at 30 days and clearance of bacteremia (days).

Time plan: 2022 Regulatory applications, free fraction of CL method. 2023-24: Inclusion, data analysis, network building, planning of ROC. With SABs´  high mortality, it is highly important that the effect of TDM is studied systematically.