scholarly journals Candida Intestinal Domination Precedes Fungal Infections Bloodstream in Allogeneic Hematopoietic Cell Transplant Patients

2019 ◽  
Vol 25 (3) ◽  
pp. S340-S341 ◽  
Author(s):  
Bing Zhai ◽  
Mihaela Ola ◽  
Nicholas L. Tosini ◽  
Sari Joshowitz ◽  
Eric Littmann ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Transplant Patients

scholarly journals Reasons for voriconazole prophylaxis discontinuation in allogeneic hematopoietic cell transplant recipients: A real-life paradigm

2020 ◽  
Vol 58 (8) ◽  
pp. 1029-1036 ◽  
Author(s):  
Shuk Ying Chan ◽  
Rachel M Hughes ◽  
Kimberly Woo ◽  
Miguel-Angel Perales ◽  
Dionysios Neofytos ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Real Life ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Cell ◽  
P Value ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Early Discontinuation ◽  
Allogeneic Hematopoietic Cell Transplant

Abstract We sought to describe the clinical experience of voriconazole as primary antifungal prophylaxis (AFP) in allogeneic hematopoietic cell transplant recipients (allo-HCTr). This was a single-center retrospective study of adult allo-HCTr (1 January 2014 to 31 December 2016) who received ≥two doses of voriconazole-AFP. Voriconazole-AFP was started on day +7 post-HCT and continued at least through day +60 post-HCT, or longer as clinically indicated. We reviewed the rate, reasons, and risk factors of voriconazole-AFP discontinuation until day-100 post-HCT. A total of 327 patients were included. Voriconazole-AFP was continued for a median of 69 days (mean: 57.9; range 1, 100): for a median of 90 days (mean :84; range 2, 100) in 180/327 (55%) in the standard-of-care (SOC) group and 20 days (mean :25.6 ; range 1, 89; P-value < .001) in 147/327 (45%) patients in the early-discontinuation-group. Early-voriconazole-AFP discontinuation was due to adverse events, drug interactions, insurance coverage, and other reasons in 101/147 (68.7%), 27 (18.4%), 13 (8.8%), and 6 (4.1%) patients, respectively. Early-voriconazole-AFP discontinuation occurred in 73/327 (22.3%) patients due to hepatotoxicity. Important predictors for early-voriconazole-AFP discontinuation included: graft-versus-host disease grade ≥2 (odds ratio [OR]: 1.9, P-value: .02), alanine-aminotransferase ≥75 IU/ml on voriconazole-administration day-14 (OR: 5.6, P-value: .02) and total bilirubin ≥1.3 mg/dl on voriconazole-administration day-7 (OR: 3.0, P-value: .03). There were 13 proven/probable invasive fungal infections by day-180 post-HCT (8/147, 5.4%, and 5/180, 2.8% in the early-discontinuation and SOC-groups, respectively; log-rank:0.13). By day-180 post HCT, 23/147 (15.6%) and 14/180 (7.8%) patients in the early-discontinuation and SOC-groups had died, respectively (log-rank:0.03). Voriconazole-AFP was discontinued in up to 45% of allo-HCTr. Hepatotoxicity during the first 2 weeks post-HCT is a significant predictor of early-voriconazole-AFP discontinuation.

Clinical considerations on posaconazole administration and therapeutic drug monitoring in allogeneic hematopoietic cell transplant recipients

2020 ◽  
Author(s):  
Mateja Kraljevic ◽  
Nina Khanna ◽  
Michael Medinger ◽  
Jakob Passweg ◽  
Stavroula Masouridi-Levrat ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Primary Objective ◽  
Hematopoietic Cell ◽  
Therapeutic Drug ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant

Abstract There is a paucity of data on posaconazole (PCZ) dosing and therapeutic-drug-monitoring (TDM) in allogeneic hematopoietic cell transplant recipients (allogeneic-HCTr). This was a 3-year retrospective multicenter study (January 1, 2016 to December 31, 2018) in adult allogeneic-HCTr who received PCZ (intravenously, IV and/or as delayed-release tablet, DRT) as prophylaxis or treatment for ≥7 consecutive days (D) with at least 1-PCZ-level available using data of the Swiss Transplant Cohort Study. The primary objective was to describe the distribution of PCZ-level and identify predictors of therapeutic PCZ-level and associations between PCZ-dosing and PCZ-level. A total of 288 patients were included: 194 (67.4%) and 94 (32.6%) received PCZ as prophylaxis and treatment, respectively, for a median of 90 days (interquartile range, IQR: 42–188.5). There were 1944 PCZ-level measurements performed, with a median PCZ level of 1.3 mg/L (IQR: 0.8-1.96). PCZ-level was <0.7 mg/L in 383/1944 (19.7%) and <1.0 mg/L in 656/1944 (33.7%) samples. PCZ-level was <0.7 mg/L in 260/1317 (19.7%) and <1.0 mg/L in 197/627 (31.4%) in patients who received PCZ-prophylaxis versus treatment, respectively. There were no significant differences in liver function tests between baseline and end-of-treatment. There were nine (3.1%) breakthrough invasive fungal infections (bIFI), with no difference in PCZ levels between patients with or without bIFI. Despite a very intensive PCZ-TDM, PCZ-levels remain below target levels in up to one-third of allogeneic-HCTr. Considering the low incidence of bIFI observed among patients with PCZ levels in the targeted range, our data challenge the clinical utility of routine universal PCZ-TDM.

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