Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition: a randomized multicentre trial. To determine the most effective and safe long-term S. aureus decolonization regimen for patients on home parenteral nutrition (HPN) with a central venous access device (CVAD).AbstractObjectivesTo determine the most effective and safe long-term S. aureus decolonization regimen for patients on home parenteral nutrition (HPN) with a central venous access device (CVAD).MethodsA randomized, open-label, multicenter clinical trial was conducted. Patients on HPN using a CVAD and carrying S. aureus were randomly assigned to a ‘search and destroy’ (SD) strategy, a quick and short, systemic antibiotic treatment, or a ‘continuous suppression’ (CS) strategy, a repeated chronic topical antibiotic treatment. The primary outcome was the proportion of patients in whom S. aureus was totally eradicated during a 1-year period. Secondary outcomes included risk factors for decolonization failure and S. aureus infection, antimicrobial resistance, adverse events, patient compliance, quality of life, and cost-effectivity.Results63 participants were included (SD 32; CS 31) between February 2018 and October 2021. The mean 1-year S. aureus decolonization rate was 39% (95% CI 25, 56) for the SD group and 61% (95% CI 44, 75) for the CS group with an OR of 2.38 (95% CI 0.92, 6.11, P = 0.07). Significantly more adverse effects related to the study medication occurred in the SD group (P = 0.01). Independent predictors for eradication failure were a S. aureus positive caregiver and presence of a (gastro)enterostomy . In three SD participants, resistance to previously administered antibiotics occurred.ConclusionsOur trial did not demonstrate an increased efficacy of a short and systemic S. aureus decolonization strategy over a continuous topical suppression treatment for patients with a CVAD. The latter may be the best option as it achieved a higher long-term decolonization rate and was well-tolerated (NCT03173053).