Staphylococcus aureus bacteraemia (SAB) is a common and severe infection, with a 90-day mortality of 24%–32%. Cloxacillin is regarded as a first-line antibiotic treatment in SAB in Sweden. However, exposure to cloxacillin in real-world hospitalised patients with SAB, most of whom are elderly patients treated outside the intensive care unit, is not well described. There are also limited data on the role of unbound cloxacillin exposure in relation to renal function or drug-induced toxicity.

This multicentre, prospective, observational clinical trial will include 95 adult patients with methicillin-susceptible S. aureus bacteraemia, treated with cloxacillin. Patients with endocarditis, polymicrobial bacteraemia or those considered unsuitable for cloxacillin treatment are excluded. Trough and peak total and unbound cloxacillin concentrations will be measured at steady state at days 2 and 7. Blood cultures will be obtained at days 2, 3, 4 and 7 to assess time to negative culture. Renal function will be assessed daily for plasma creatinine and at days 1 and 6 for cystatin C and for 12-hour urine creatinine clearance. In a novel approach to detecting nephrotoxicity, renal tubular damage biomarkers will be measured at days 1 and 6 (KIM-1, N-acetyl-β-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, urine cystatin C, alpha-1-microglobulin). Detection of neurologic symptoms such as confusion, tremor, hallucinations and convulsions, as well as consciousness, will be monitored daily using a structured evaluation form.

We aim to investigate to which extent target attainment (100% of the dosing interval during which the free (unbound) drug concentration exceeds the minimum inhibitory concentration) is achieved with standard dosing of cloxacillin in a real-world cohort of hospitalised patients with SAB, and whether initial renal function can predict who is at risk for underdosing or overdosing. We will also explore whether neurological or renal damage is prevalent and associated with cloxacillin levels.

Ethics approval has been granted by the Swedish Ethical Review Authority (EUCT 2023-505148-20-00) as part of a low-intervention clinical trial approval according to EU regulation 536/2014. Results will be disseminated in a peer-reviewed journal and at academic conferences.

EUCT 2023-505148-20-00.

Opioid analgesic medications play a critical role in pain management but are associated with significant risks, including addiction. General practitioners in primary care account for a substantial proportion of opioid prescriptions, and prescribing practices may not always fully align with clinical guidelines. Given the limited evidence supporting long-term opioid use for chronic non-cancer pain, there is a pressing need for interventions that promote safer, guideline-concordant prescribing. The Smarta Val (Smart Choices) trial will evaluate whether a new multicomponent intervention, comprising an educational seminar, written materials and feedback on prescribing over 12 months, can improve opioid prescribing practices in primary care.

This cluster randomised pragmatic trial will assess changes in opioid prescribing across primary healthcare centres (PHCCs) in Stockholm, Sweden. Consenting PHCCs will be randomised 1:1 to either the intervention group, receiving the multicomponent intervention, or the active control group, receiving a leaflet on prescribing recommendations. A sample size of 24 PHCCs per group is required to detect differences in opioid prescribing between groups. A third group of non-randomised observational reference PHCCs will be included to provide contextual information on prescribing practices during the study period. Data sources include regional healthcare databases, baseline and 12-month follow-up questionnaires, and an intervention delivery form. The primary outcome is the change in prescription of opioids at 12 months. Secondary outcomes are the change in prescription of opioids at 24 months and the change in the specific opioid substances prescribed at 12 months.

The study has been approved by the Swedish Ethical Review Authority (Dnr 2021-06739-01). Participation in the study requires informed consent from PHCC managers in the intervention and active control groups. Results will be disseminated through international peer-reviewed journals and conference presentations.

NCT05577026.