Dataset Information

Targeted versus universal antifungal prophylaxis among liver transplant recipients.

ABSTRACT: Guidelines recommend targeted antifungal prophylaxis for liver transplant (LT) recipients based on tiers of risk, rather than universal prophylaxis. The feasibility and efficacy of tiered, targeted prophylaxis is not well established. We performed a retrospective study of LT recipients who received targeted prophylaxis (n = 145; voriconazole [VORI; 54%], fluconazole [8%], no antifungal [38%]) versus universal VORI prophylaxis (n = 237). Median durations of targeted and universal prophylaxis were 11 and 6 days, respectively (p < 0.0001). The incidence of invasive fungal infections (IFIs) in targeted and universal groups was 6.9% and 4.2% (p = 0.34). Overall, intra-abdominal candidiasis (73%) was the most common IFI. Posttransplant bile leaks (p = 0.001) and living donor transplants (p = 0.04) were independent risk factors for IFI. IFIs occurred in 6% of high-risk transplants who received prophylaxis and 4% of low-risk transplants who did not receive prophylaxis (p = 1.0). Mortality rates (100 days) were 10% (targeted) and 7% (universal) (p = 0.26); attributable mortality due to IFI was 10%. Compliance with prophylaxis recommendations was 97%. Prophylaxis was discontinued for toxicity in 2% of patients. Targeted antifungal prophylaxis in LT recipients was feasible and safe, effectively prevented IFIs and reduced the number of patients exposed to antifungals. Bile leaks and living donor transplants should be considered high-risk indications for prophylaxis.

SUBMITTER: Eschenauer GA

PROVIDER: S-EPMC4365781 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeted versus universal antifungal prophylaxis among liver transplant recipients.

Eschenauer G A GA Kwak E J EJ Humar A A Potoski B A BA Clarke L G LG Shields R K RK Abdel-Massih R R Silveira F P FP Vergidis P P Clancy C J CJ Nguyen M H MH

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20141030 1

Guidelines recommend targeted antifungal prophylaxis for liver transplant (LT) recipients based on tiers of risk, rather than universal prophylaxis. The feasibility and efficacy of tiered, targeted prophylaxis is not well established. We performed a retrospective study of LT recipients who received targeted prophylaxis (n = 145; voriconazole [VORI; 54%], fluconazole [8%], no antifungal [38%]) versus universal VORI prophylaxis (n = 237). Median durations of targeted and universal prophylaxis were ...[more]

PMID: 25359455

Similar Datasets

Project description:Background & aimsProphylaxis with nucleos(t)ide analogues (NUCs) and hepatitis B immunoglobulin (HBIG) has decreased the rate of HBV recurrence after orthotopic liver transplantation (OLT), but the duration of this prophylaxis remains debated. Our aim was to investigate the recurrence of both intrahepatic and serum HBV markers after OLT in patients receiving long-term NUC and HBIG prophylaxis.MethodsA total of 31 HBV-positive patients benefiting from OLT were prospectively enrolled in five French centres between 2012 and 2015. Tissue samples from the native liver, liver reperfusion biopsy, and 12-month post-OLT (M12) biopsy were collected. Intrahepatic HBV markers were quantified using Droplet Digital PCR. Serum hepatitis B core-related antigen (HBcrAg) and HBsAg were quantified using the Lumipulse platform.ResultsAmong the 31 patients, 26 were HBeAg negative and 28 had undetectable serum HBV DNA at OLT. All patients received HBIG and NUC after OLT, and serum HBV DNA was undetectable at M12. Of the 27 available native livers, 26 had detectable total HBV DNA (median, 0.045 copies/cell), 21 were positive for cccDNA (0.001 copies/cell), and 19 were positive for 3.5-kb HBV RNA (0.0004 copies/cell). Among the 14 sequential reperfusion and M12 biopsies, seven were positive for HBV markers on the reperfusion sampling, and six of them were also positive at M12. Of the 27 patients with available serum samples at M12, eight were positive for HBcrAg and five were positive for HBsAg by ultrasensitive quantification, although they were negative by conventional techniques. Overall, among the 17 patients having a matched biopsy and serum sample at M12, only one had undetectable HBV markers in both the liver and serum.ConclusionsOur results demonstrate a very early detection of viral genome in the graft and intrahepatic viral recurrence despite NUC and HBIG prophylaxis.Clinical trials registrationThis study is registered at ClinicalTrials.gov (NCT02602847).Impact and implicationsIn this work, we show that, despite the recommended prophylaxis based on NUC and HBIG, HBV can infect the new liver very rapidly after transplantation. Twelve months after transplantation, the majority of patients had at least one HBV marker detected in either serum or the liver. Therefore, our results demonstrate early intrahepatic viral recurrence despite NUC and HBIG therapy and underline the importance of an optimal patient compliance to the antiviral prophylaxis to prevent viral rebound.

Project description:Voriconazole is frequently discontinued prematurely as primary antifungal prophylaxis (AFP) in allogeneic hematopoietic cell transplant (HCT) recipients due to adverse events. Limited data exists for isavuconazole as AFP. We analyzed adult HCT recipients who received voriconazole or isavuconazole AFP to estimate rate of premature AFP discontinuation, identify risk factors for premature AFP discontinuation, and compare incidence of invasive fungal infection (IFI) and survival at day + 180 post-HCT between patients who received voriconazole/isavuconazole-AFP. This was a propensity score matched cohort analysis of 210 HCT-recipients who received voriconazole-AFP (9/1/2014-12/31/2016; voriconazole-cohort), and 95 HCT-recipients who received isavuconazole-AFP (5/1/2017-10/31/2018; isavuconazole-cohort). AFP discontinuation for any reason prior to completion was defined as "premature". Median (interquartile range, IQR) duration of AFP was longer in the isavuconazole-cohort (94 days, 87-100) vs. the voriconazole-cohort (76 days, 23-94; P-value < 0.0001). Premature AFP discontinuation was more frequent in the voriconazole-cohort (92/210, 43.8%) vs. the isavuconazole-cohort (14/95, 14.7%; P-value < 0.0001). The most common reason for premature discontinuation was biochemical hepatotoxicity (voriconazole-cohort: 48/210, 22.8% vs. isavuconazole-cohort: 5/95, 5.26%; P-value = 0.0002). Transaminase values between baseline and end-of-treatment (EOT) and up to 14 days post-EOT significantly increased in the voriconazole-cohort, but remained unchanged in the isavuconazole-cohort. The incidence of IFI at day + 180 was 2.9% (6/210) and 3.2% (3/95) in the voriconazole-cohort and isavuconazole-cohort, respectively (P-value = 0.881). All-cause mortality at day + 180 was 2.4% (5/210) and 6.3% (6/95) in the voriconazole-cohort and isavuconazole-cohort, respectively (P-value = 0.089). When compared to voriconazole, isavuconazole was a safer and as effective primary AFP during the first 3 months after HCT.Lay summaryWhen compared to voriconazole, isavuconazole is a safer and as effective primary antifungal prophylaxis during the first 3 months after allogeneic hematopoietic cell transplant, with lower rates of hepatotoxicity, and similar rates of fungal infections and all-cause mortality.

Dataset Information

Targeted versus universal antifungal prophylaxis among liver transplant recipients.

Publications

Targeted versus universal antifungal prophylaxis among liver transplant recipients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets