Echinocandins for antifungal prophylaxis in liver transplant recipients: Advance in the field or variation on a theme?

Koval, Christine

doi:10.1002/lt.24419

Cited by 6 publications

(7 citation statements)

References 17 publications

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“…In this regard, our sensitivity analysis found a significantly higher risk of breakthrough IFI with echinocandins after the exclusion of the study by Fortún et al, 23 in which the proportion of breakthrough IFI with fluconazole was higher compared to caspofungin (9.2% vs 2.1%), especially in OLT recipients requiring renal replacement therapy (RRT). High variability in fluconazole exposure was reported among critically ill patients, with suboptimal concentrations in up to 33% of cases 32,33 . Furthermore, fluconazole dosage of 400 mg and 600–800 mg daily are required to achieve optimal concentrations in critically ill patients with poor/moderate renal function or receiving RRT, respectively 34,35 .…”

Section: Discussionmentioning

confidence: 99%

Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta‐analysis

Gatti

Rinaldi

Ferraro

et al. 2021

Mycoses

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Introduction:Although echinocandins are recommended as first-line prophylaxis for high-risk orthotopic liver transplant (OLT) recipients, occurrence of breakthroughinvasive fungal infections (IFIs) remains a serious concern. We aim to assess the risk of breakthrough IFIs among OLT recipients exposed to prophylaxis with echinocandins compared to other antifungals. Materials and methods: Two authors independently searched PubMed-MEDLINE, Embase, study registries and reference lists from inception to March 2021, to retrieve randomised controlled trials (RCTs) or observational studies comparing efficacy and safety of echinocandins vs other antifungals for prophylaxis in OLT recipients. Data were independently extracted from two authors, and the quality of included studies was independently assessed according to ROB 2.0 tool for RCTs and ROBINS-I tool for observational studies. The primary outcome was occurrence of breakthrough IFI at the end of prophylaxis (EOP).Results: 698 articles were screened, and ten studies (3 RCTs and 7 observational) were included. No difference between echinocandins and other antifungals in terms of breakthrough IFIs at the EOP emerged both from RCTs (odds ratio [OR] 0.85, 95% CI 0.24-2.99) and observational studies (OR 1.43, 95% CI 0.28-7.40). No difference emerged also for secondary outcomes. In the subgroup comparison between echinocandins and polyenes, a trend for higher risk of breakthrough IFI at the EOP (OR 4.82, 95% CI 0.97-24.03) was noted.Conclusions: Echinocandins do not seem to be associated with increased risk of breakthrough IFIs in OLT recipients. However, the large diversity in the comparator group hinders a definitive interpretation. Further studies exploring the relationship between echinocandin use and breakthrough IFIs according to specific comparators are warranted.

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Section: Discussionmentioning

confidence: 99%

Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta‐analysis

Gatti

Rinaldi

Ferraro

et al. 2021

Mycoses

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“…Fungal infection after liver transplant increases morbidity and mortality . Fungal prophylaxis after liver transplant reduces rates of fungal infection, however, this has not been shown to definitively improve mortality, which has led to controversy regarding the antifungal of choice . Indeed, one of the major arguments for the use of enchinocandal prophylaxis is the thought that the broader antifungal spectrum will reduce breakthrough IFI, without the toxicities of other mold‐active agents, such as amphotericin and voriconazole.…”

Section: Discussionmentioning

confidence: 99%

A targeted fungal prophylaxis protocol with static dosed fluconazole significantly reduces invasive fungal infection after liver transplantation

Jorgenson

Descourouez

Marka

et al. 2019

Transplant Infectious Dis

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Background: Invasive fungal infection (IFI) after liver transplant (LTx) is associated with extensive morbidity and mortality. Targeted prophylaxis reduces risk, but qualifying criteria, drug of choice and regimen are unclear and compliance is inconsistent. Objective: Assess the impact of a risk factor-based fungal prophylaxis protocol (FPP) after LTx on fungal infection rates, fungal epidemiology, and transplant outcomes. Methods: Observational cohort study of adult LTx recipients between July 1, 2009, and June 30, 2017. Patients in the FPP group were given a set dose of 400 mg fluconazole without renal adjustment on POD 1-14 via pharmacist delegation protocol. Results:One hundred and eighty-nine patients met inclusion criteria; 50 in the FPP and 139 in the pre-implementation comparator group. Of those who would be considered high-risk, 22.3% received antifungal prophylaxis prior to FPP implementation vs 92% after implementation (P < .0001). There were significantly fewer fungal infections in the FPP group at 1 year (12.5% vs 26.6%, P = .03). IFI in the pre-implementation control group was due to Candida species in 95% of cases; 30% were species with reduced fluconazole susceptibility. IFI in the FPP group was due to Candida species in all cases, and no isolates had reduced fluconazole susceptibility. Aspergillus did not account for any IFI between the groups. One-year patient and graft survival were similar between groups. In a multivariable model accounting for patient and donor age, donor type, MELD, and cold ischemic time, FPP was protective against fungal infection (HR 0.3, P = .015). FPP did not significantly impact graft survival (HR 0.4, P = .14), but trended toward improved patient survival. (HR 0.18, P = .06).Conclusion: Implementation of a targeted FPP utilizing static dosing of fluconazole 400 mg × 14 days to those that meet high-risk criteria significantly reduces invasive fungal infection after liver transplant. Use of this protocol did not adversely affect fungal epidemiology and may have a positive impact on allograft and patient survival.Future large prospective studies are needed to better evaluate survival impact. K E Y W O R D Santifungals, fungal infections, hepatic, prophylaxis, transplantation

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“…14 Traditionally, azoles have been the preferred anti-fungal agents; more recent evidence suggests that echinocandins may reduce the incidence of peri-transplant invasive fungal infections; however, no difference in graft loss or mortality has been identified in comparative studies between azoles and echinocandins. 15 Additional…”

Section: Management Of Infectious Diseasesmentioning

confidence: 99%

Medical Management after Liver Transplantation

Dave

Ajmera

2019

Dig Dis Interv

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Medical management of the liver transplant recipient requires consideration of the complex interactions between the transplanted liver, immunosuppression and all organ systems. An aging transplant population, improvement in long-term liver transplant outcomes, and the increase in nonalcoholic fatty liver disease as an indication for transplant have amplified the number of co-morbidities among post-transplant patients. In addition to balancing immunosuppression with infection risk, medical management of the transplanted patient includes monitoring for, and treating, recurrence of the primary liver disease, metabolic syndrome, cardiovascular disease, and post-transplant neurologic and renal dysfunction. Additionally, general healthcare maintenance such as management of osteoporosis, immunizations, and screening for malignancy are essential in this high-risk population. In this review, we summarize the evidence behind best practices for the current medical management of the post liver transplant patient.

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Echinocandins for antifungal prophylaxis in liver transplant recipients: Advance in the field or variation on a theme?

Cited by 6 publications

References 17 publications

Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta‐analysis

Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta‐analysis

A targeted fungal prophylaxis protocol with static dosed fluconazole significantly reduces invasive fungal infection after liver transplantation

Medical Management after Liver Transplantation

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