Peritoneal dialysis-associated peritonitis presenting with Ralstonia pickettii infection: A novel series of three cases during the COVID-19 pandemic.

Peritoneal dialysis (PD)-associated peritonitis secondary to Ralstonia infection is very rare. Ralstonia pickettii is an organism that can grow in contaminated saline, water, chlorhexidine, and other medical products used in laboratories and the clinical setting. Infective endocarditis, prosthetic joint, and severe chest infections are previously reported with R. pickettii infection. We report a novel series of three cases diagnosed with PD-associated peritonitis caused by R. pickettii, where the cases appeared consecutively to our unit during a span of 4 weeks. During the COVID-19 pandemic, there were increased uses of non-sterile gloves by clinical staff as a form of personal protective equipment throughout patient interaction and PD exchange, as recommended by local hospital policy for all staff attending to patient care. A multidisciplinary team root cause analysis of our cases suggested non-sterile gloves being the likely source of environmental contamination, leading to PD-associated peritonitis caused by R. pickettii in this scenario.

A pilot project evaluating a fixed drainage system (U-Drain) for automated peritoneal dialysis.

U-Drain is a fixed drainage system for automated peritoneal dialysis (APD) connecting the dialysis effluent outflow directly to the household drainage system thus avoiding the need for drain bags, with considerable potential advantages for patient convenience and reduction of plastic clinical waste. Here we present a pilot project reporting on U-Drain patient and staff experience based on questionnaires and on the safety of the technology derived from analysis of characteristics of peritonitis episodes. Overall, 15 patients were included in the pilot project and were followed up over 3 years; 11 patients completed a questionnaire exploring their experiences of APD and U-Drain. A family member 55%, carer 10%, healthcare assistant 10% and patient themselves 25% would normally carry the full drainage bags for disposal. Following the installation of U-Drain, 90% of patients reported that the system saved them time setting up and clearing the machine after dialysis, 80% noted a reduction in storage space required for consumables and all patients noted a reduction in non-recyclable waste requiring disposal. All patients who completed the questionnaire were very satisfied with the installation. All staff members who completed the questionnaire reported that their role was easier and the system was time saving. In total, there were 8 peritonitis episodes, including 2 recurrent infections due to biofilm, over 313 patient months follow up. There was no increase in incidence of peritonitis infection (0.3 episodes per year at risk) compared to that in the unit's population (0.64, 0.42 and 0.5 episodes per year at risk for the years 2017, 2018 and 2019, respectively) or delays in diagnosis. Approximately 0.8 kg of non-recyclable clinical waste was saved per treatment day from domestic waste by avoiding the use of PD drain bags. This pilot demonstrates increased patient satisfaction and acceptable safety profile of U-Drain technology.

Safety, tolerability, and pharmacokinetics of amuvatinib from three phase 1 clinical studies in healthy volunteers.

PURPOSE: Amuvatinib is a multi-targeted tyrosine kinase inhibitor with activity that also disrupts DNA damage repair through suppression of homologous recombination protein Rad51. Amuvatinib dry-powder capsules (DPC) showed evidence of activity in early Phase 1 cancer studies but low systemic exposure. The purposes of the studies were to investigate the cause of low exposure, develop, and test an alternative formulation with improved exposure, and establish the dose to be tested in future studies in cancer patients. METHODS: Three studies were conducted in a total of 58 healthy subjects: a food-effect study using amuvatinib DPC, a single-dose pharmacokinetic study comparing amuvatinib DPC to a new lipid-suspension capsules (LSC), and a multiple-dose pharmacokinetic study using amuvatinib LSC. RESULTS: A high-fat meal administered with amuvatinib DPC increased the rate and extent of absorption compared to the Fasted state, a 183 and 118% increase in the mean C(max) and AUC(0-∞) of amuvatinib, respectively. The single-dose pharmacokinetics of amuvatinib LSC resulted in an approximately two-third-fold increased exposure (AUC) compared with amuvatinib DPC. The multiple-dose pharmacokinetics of the amuvatinib LSC 300 mg administered every 8 h exhibited improved accumulation compared with the 12-h regimens and achieved presumed therapeutic level safely with no serious or severe adverse events reported. No subject discontinued treatment due to an adverse event. CONCLUSION: Amuvatinib LSC, 300 mg every 8 h, is being studied in cancer patients based on the improved exposure and similar safety profile to amuvatinib DPC. A lipid-based formulation approach may be a useful tool for other low aqueous soluble compounds.