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1.
Bone Marrow Transplant ; 57(9): 1373-1381, 2022 09.
Article in English | MEDLINE | ID: mdl-35661156

ABSTRACT

Earlier studies have suggested that severe intestinal mucositis (IM; citrulline < 10 µmol/L) is an independent risk factor for bloodstream infections (BSI) after cytotoxic therapy. Our aim was to grade IM in patients receiving commonly used chemotherapy and conditioning regimens, and characterize its relationship with BSI incidence. In a retrospective analysis of remission induction (RI) chemotherapy, or conditioning for autologous and allogeneic hematopoietic stem cell transplantation (HSCT; myeloablative conditioning [MAC] and non-myeloablative and reduced-intensity conditioning [NMA/RIC]), data were collected on central venous catheter (CVC) characteristics and BSI. The relationship between BSI occurrence and the degree of IM (determined by citrulline levels) and neutropenia was analyzed. In 626 CVC episodes, 268 (42.8%) laboratory-confirmed BSIs (LCBIs) occurred, classified as mucosal barrier injury (MBI)-LCBIs in 179 (28.6%) episodes, central line-associated BSIs in 113 (18.1%) episodes, and catheter-related BSIs in 55 (8.8%) episodes. In NMA/RIC, the mean duration of hypocitrullinemia was 0.77 days, with LCBI and MBI-LCBI occurring in 11.1% and 4.8% of episodes. In autologous HSCT, RI, and MAC allogeneic HSCT, LCBI and MBI-LCBI occurred frequently (40.0-63.8% and 22.8-53.2% of episodes, respectively) and the mean duration of hypocitrullinemia was significantly higher (9.2-13.8 days). There was a strong correlation between LCBI and the duration of hypocitrullinemia (Pearson's correlation coefficient R = 0.96), as opposed to the relationship between LCBI and the duration of neutropenia (R = 0.42). We conclude that citrulline can be used to grade BSI risk for commonly used intensive treatment regimens.


Subject(s)
Bacteremia , Catheter-Related Infections , Hematopoietic Stem Cell Transplantation , Infections , Mucositis , Neutropenia , Sepsis , Bacteremia/etiology , Biomarkers , Catheter-Related Infections/epidemiology , Catheter-Related Infections/etiology , Citrulline , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infections/etiology , Mucositis/etiology , Neutropenia/etiology , Retrospective Studies
2.
Sci Rep ; 12(1): 6803, 2022 05 11.
Article in English | MEDLINE | ID: mdl-35546555

ABSTRACT

High-dose chemotherapy causes intestinal inflammation and subsequent breakdown of the mucosal barrier, permitting translocation of enteric pathogens, clinically manifesting as fever. Antibiotics are mainstay for controlling these complications, however, they are increasingly recognized for their detrimental effects, including antimicrobial resistance and dysbiosis. Here, we show that mucosal barrier injury induced by the mucotoxic chemotherapeutic agent, high-dose melphalan (HDM), is characterized by hyper-active IL-1b/CXCL1/neutrophil signaling. Inhibition of this pathway with IL-1RA, anakinra, minimized the duration and intensity of mucosal barrier injury and accompanying clinical symptoms, including diarrhea, weight loss and fever in rats. 16S analysis of fecal microbiome demonstrated a more stable composition in rats receiving anakinra, with reduced pathogen expansion. In parallel, we report through Phase IIA investigation that anakinra is safe in stem cell transplant patients with multiple myeloma after HDM. Ramping-up anakinra (100-300 mg administered intravenously for 15 days) did not cause any adverse events or dose limiting toxicities, nor did it change time to neutrophil recovery. Our results reinforce that strengthening the mucosal barrier may be an effective supportive care strategy to mitigate local and systemic clinical consequences of HDM. We are now conducting a Phase IIB multicenter, placebo-controlled, double-blinded trial to assess clinical efficacy of anakinra (AFFECT-2).Trial registration: ClinicalTrials.gov identifier: NCT03233776.


Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Animals , Fever/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Interleukin 1 Receptor Antagonist Protein , Interleukin-1 , Melphalan/therapeutic use , Multiple Myeloma/diagnosis , Rats , Tumor Microenvironment
3.
J Hosp Infect ; 105(4): 686-690, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32339616

ABSTRACT

In the Netherlands, the PREZIES surveillance is used for registration and surveillance of central venous catheter (CVC) -related bloodstream infections (CRBSI). We investigated how this Dutch definition correlated with internationally used definitions for CRBSI, central line-associated bloodstream infections (CLABSI) and mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBI). We determined that the Dutch PREZIES definition of CRBSI is appropriate for surveillance control of CVC care bundle use in haemato-oncology patients managed with multi-lumen CVCs.


Subject(s)
Catheter-Related Infections/microbiology , Catheterization, Central Venous/adverse effects , Epidemiological Monitoring , Hematologic Neoplasms/complications , Sepsis/microbiology , Adult , Aged , Catheter-Related Infections/etiology , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Netherlands , Retrospective Studies , Sepsis/etiology
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