Genomic characterization of methicillin-susceptible Staphylococcus aureus carriage in patients on home parenteral nutrition and their caregivers.

In this prospective study, patients on home parenteral nutrition were twice as likely to be colonized with Staphylococcus aureus if their caregivers were also carriers. Among S. aureus-positive patients and their caregivers, molecular analysis showed 68% genetically related strains. Despite decolonization, genetically related strains reappeared in 70% of patients.

Oral antimicrobial agents in patients with short bowel syndrome: worth a try!

BACKGROUND: The use of oral antimicrobial agents in patients with short bowel syndrome (SBS) is challenging due to the changes in gastrointestinal anatomy that may result in diminished absorption and altered drug bioavailability. Prospective studies evaluating bioavailability of antimicrobial agents after oral administration in SBS patients are lacking. OBJECTIVES: To determine the bioavailability of orally administered antimicrobial agents commonly used for treatment in SBS patients to guide clinical decision making when faced with infections. METHODS: We performed an explorative, clinical study investigating the pharmacokinetics (PK) of clindamycin, ciprofloxacin, flucloxacillin and fluconazole in SBS patients with intestinal failure. Participants received a combination of two antimicrobial agents simultaneously. To determine the oral bioavailability, participants received a single oral and IV dose of both agents on two occasions, after which they underwent intensive PK sampling on six predefined time points up to 12 hours after administration. Primary outcome was the oral bioavailability of these antimicrobial agents. Secondary outcomes were intravenous PK characteristics following non-compartmental analysis. RESULTS: Eighteen SBS patients were included: the mean (SD) age was 59 (17) years and 61% of participants were female. The median observed (IQR) bioavailability of ciprofloxacin, clindamycin, flucloxacillin and fluconazole were 36% (24-50), 93% (56-106), 50% (32-76) and 98% (61-107), respectively. CONCLUSION: The bioavailability of selected antimicrobial agents in certain patients with SBS appeared to be better than expected, providing a feasible treatment option. Due to the large observed differences between patients, therapeutic drug monitoring should be part of the treatment to safeguard adequate exposure in all patients. TRIAL REGISTRATION: Registered in the Dutch Trial Register (NL7796) and EudraCT number 2019-002587-28.

Randomized clinical trial: Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition.

BACKGROUND & AIMS: Staphylococcus aureus decolonization has proven successful in prevention of S. aureus infections and is a key strategy to maintain venous access and avoid hospitalization in patients receiving home parenteral nutrition (HPN). We aimed to determine the most effective and safe long-term S. aureus decolonization regimen. METHODS: A randomized, open-label, multicenter clinical trial was conducted. Adult intestinal failure patients with HPN support and carrying S. aureus were randomly assigned to a 'continuous suppression' (CS) strategy, a repeated chronic topical antibiotic treatment or a 'search and destroy' (SD) strategy, a short and systemic antibiotic treatment. 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 infections, antimicrobial resistance, adverse events, patient compliance and cost-effectivity. RESULTS: 63 participants were included (CS 31; SD 32). The mean 1-year S. aureus decolonization rate was 61% (95% CI 44, 75) for the CS group and 39% (95% CI 25, 56) for the SD group with an OR of 2.38 (95% CI 0.92, 6.11, P = 0.07). More adverse effects occurred in the SD group (P = 0.01). Predictors for eradication failure were a S. aureus positive caregiver and presence of a (gastro)enterostomy. CONCLUSION: We did not demonstrate an increased efficacy of a short and systemic S. aureus decolonization strategy over a continuous topical suppression treatment. The latter may be the best option for HPN patients as it achieved a higher long-term decolonization rate and was well-tolerated (NCT03173053).