Neonatal Elizabethkingia anophelis meningitis originating from the water reservoir of an automated infant milk dispenser, the Netherlands, February 2024.

Elizabethkingia anophelis is a multidrug-resistant pathogen causing high mortality and morbidity in adults with comorbidities and neonates. We report a Dutch case of E. anophelis meningitis in a neonate, clonally related to samples taken from an automated infant milk dispenser located at the family's residence. We inform about the emergence of E. anophelis and suggest molecular surveillance in hospitals and other health settings. This is the first case connecting an automated formula dispenser to an invasive infection in a neonate.

Association between anti-thymocyte globulin exposure and survival outcomes in adult unrelated haemopoietic cell transplantation: a multicentre, retrospective, pharmacodynamic cohort analysis.

BACKGROUND: Anti-thymocyte globulin (ATG) is used to prevent graft-versus-host disease (GvHD) after allogeneic haemopoietic cell transplantation (HCT). However, ATG can also cause delayed immune reconstitution of T cells, negatively affecting survival. We studied the relation between exposure to ATG and clinical outcomes in adult patients with acute leukaemia and myelodysplastic syndrome. METHODS: We did a retrospective, pharmacokinetic-pharmacodynamic analysis of data from patients with acute lymphoid leukaemia, acute myeloid leukaemia, or myelodysplastic syndrome receiving their first T-cell repleted allogeneic peripheral blood stem cell HCT with ATG (thymoglobulin) as part of non-myeloablative conditioning from March 1, 2004, to June 1, 2015. Patients received a cumulative intravenous dose of 8 mg/kg divided over 4 days, starting on day -8 before HCT. Active ATG concentrations were measured using a validated bioassay and pharmacokinetic exposure measures (maximum concentration, concentration at time of infusion of the graft, time to reach a concentration of 1 arbitary unit [AU] per day/mL, area under the curve [AUC], and the AUC before and after HCT) were calculated with a validated population pharmacokinetic model. The main outcome of interest was 5-year overall survival, defined as days to death from any cause or last follow-up. Other outcomes were relapse-related mortality, non-relapse mortality, event-free survival, acute and chronic GvHD, and assessment of current and optimum dosing. We used Cox proportional hazard models and Fine-Gray competing risk models for the analyses. FINDINGS: 146 patients were included. ATG exposure after HCT was shown to be the best predictor for 5-year overall survival. Optimum exposure after transplantation was determined to be 60-95 AU per day/mL. Estimated 5-year overall survival in the group who had optimum exposure (69%, 95% CI 55-86) was significantly higher than in the group who had below optimum exposure (32%, 20-51, p=0·00037; hazard ratio [HR] 2·41, 95% CI 1·15-5·06, p=0·020) and above optimum exposure (48%, 37-62, p=0·030; HR 2·11, 95% CI 1·04-4·27, p=0·038). Patients in the optimum exposure group had a greater chance of event-free survival than those in the below optimum exposure group (HR 2·54, 95% CI 1·29-5·00, p=0·007; HR for the above optimum group: 1·83, 0·97-3·47, p=0·063). Above-optimum exposure led to higher relapse-related mortality compared with optimum exposure (HR 2·66, 95% CI 1·12-6·31; p=0·027). Below optimum exposure increased non-relapse mortality compared with optimum exposure (HR 4·36, 95% CI 1·60-11·88; p=0·0040), grade 3-4 acute GvHD (3·09, 1·12-8·53; p=0·029), but not chronic GvHD (2·38, 0·93-6·08; p=0·070). Modelled dosing based on absolute lymphocyte counts led to higher optimum target attainment than did weight-based dosing. INTERPRETATION: Exposure to ATG affects survival after HCT in adults, stressing the importance of optimum ATG dosing. Individualised dosing of ATG, based on lymphocyte counts rather than bodyweight, might improve survival chances after HCT. FUNDING: Netherlands Organization for Health Research and Development and Queen Wilhelma Fund for Cancer Research.

Platelet Activation Test in Unprocessed Blood (Pac-t-UB) to Monitor Platelet Concentrates and Whole Blood of Thrombocytopenic Patients.

BACKGROUND: Platelet concentrate transfusion is the standard treatment for hemato-oncology patients to compensate for thrombocytopenia. We have developed a novel platelet activation test in anticoagulated unprocessed blood (pac-t-UB) to determine platelet function in platelet concentrates and in blood of thrombocytopenic patients. METHODS: We have measured platelet activity in a platelet concentrate and in anticoagulated unprocessed blood of a post-transfusion thrombocytopenic patient. RESULTS: Our data show time-dependent platelet activation by GPVI agonist (collagen related peptide; CRP), PAR-1 agonist (SFLLRN), P2Y12 agonist (ADP), and thromboxane receptor agonist (U46619) in a platelet concentrate. Furthermore, pac-t-UB showed time-dependent platelet activation in unprocessed blood of a post-transfusion patient with thrombocytopenia. Testing platelet function by different agonists in relation to storage show that 3-day-old platelet concentrates are still reactive to the studied agonists. This reactivity rapidly drops for each agonists during longer storage. DISCUSSION: Pac-t-UB is a novel tool to estimate platelet function by different agonists in platelet concentrates and in unprocessed blood of thrombocytopenic patients. In the near future, we will validate whether pac-t-UB is an adequate test to monitor the quality of platelet concentrates and whether pac-t-UB predicts the bleeding risk of transfused thrombocytopenic patients.