Low‐dose amphotericin for prevention of serious fungal infection following liver transplantation

Shah, Tahir; Lai, Weisi; Gow, Paul J; Leeming, Jack; Mutimer, David

doi:10.1111/j.1399-3062.2005.00108.x

Cited by 26 publications

(17 citation statements)

References 23 publications

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“…The pathogens causing IFI in our study were consistent with previous reports(2, 5–8, 18, 19). Yeasts ( Candida spp., Cryptococcus neoformans and Saccharomyces cerevisiae ) accounted for 91% (21/23) of disease-causing isolates.…”

Section: Discussionsupporting

confidence: 93%

“…The observation that IFIs in low-risk patients were sufficiently uncommon as to not require prophylaxis (Supplemental Table 1)(4, 8, 16) supports AST and IDSA recommendations for targeted prophylaxis in liver transplantation(9–11). Specific definitions of “high-risk” liver transplant recipients differ dramatically across studies; nevertheless, our data clearly verify that antifungal prophylaxis in this population is effective (Supplemental Table 2)(5–8, 17–19). In particular, our IFI rate of 6% among high-risk patients compares favorably to rates of 15–35% in studies of high-risk patients not receiving prophylaxis(6, 20).…”

Section: Discussionsupporting

confidence: 56%

“…The epidemiology of IFIs has changed in the recent era of liver transplantation, as surgical techniques and immunosuppressive and antifungal prophylaxis strategies have evolved(4). Over the past 10 years, the rate of IFIs has decreased to <10%(5–8),and risk factors such as retransplant, post-transplant renal failure requiring renal replacement therapy, and reoperation have been consistently identified(2). While the predominant pathogens remain consistent with older cohorts, the majority of infections due to Aspergillus spp.…”

Section: Introductionmentioning

confidence: 99%

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Targeted Versus Universal Antifungal Prophylaxis Among Liver Transplant Recipients

Eschenauer

Kwak

Humar

et al. 2015

American Journal of Transplantation

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Guidelines recommend targeted antifungal prophylaxis for liver transplant 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 liver transplant recipients who received targeted prophylaxis (n=145; voriconazole (54%), fluconazole (8%), no antifungal (38%))vs. universal voriconazole 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. Post-transplant 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 liver transplant 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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

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Targeted Versus Universal Antifungal Prophylaxis Among Liver Transplant Recipients

Eschenauer

Kwak

Humar

et al. 2015

American Journal of Transplantation

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“…The emergence of molds as an important pathogen in recipients of liver transplantation and the growing presence of other mycelial molds as pathogens were the most important factors. Other recent studies have examined the effectiveness of ABLC, showing a lower incidence of severe fungal infections as well as increased likelihood of successful discharge from the intensive care unit in liver transplant recipients who receive ABLC as prophylaxis 26–28…”

Section: Discussionmentioning

confidence: 99%

Effect of prophylaxis on fungal infection and costs for high-risk liver transplant recipients

et al. 2007

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We sought to determine whether the prophylactic use of amphotericin B products (conventional amphotericin B and liposomal amphotericin B) reduces the incidence of fungal infections in high-risk liver transplant recipients, and if so, whether this lowers the cost of care. The study sample comprised 232 adult orthotopic liver transplants performed from 1994 to 2005 at a single center for patients classified as being at high risk for fungal infections. High-risk patients who received transplants with a prophylaxis regimen of amphotericin B (n ϭ 58 transplants) were compared with high-risk patients who received no prophylaxis (n ϭ 174 transplants). Fungal infections occurred in 3 transplants (5.17%) of those who received amphotericin B and 28 transplants (16.09%) in those without prophylaxis (P ϭ 0.0432). Regression models were used to analyze fungal infection and costs for the 232 high-risk transplants. Failure to offer prophylaxis conferred a 4-fold greater risk of fungal infection (P ϭ 0.046) compared with those who received amphotericin B. A fungal infection in a high-risk recipient increased mean costs by 46.48%. The indirect effect of prophylaxis (operating through infection reduction) is estimated to reduce overall costs in high-risk patients by 8.73%.

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“…However, one trial demonstrated that prophylaxis with aerosolized ABLC and fluconazole in HSCT recipients was well-tolerated, with 1 of 40 patients developing a breakthrough IFI while receiving study medication (mean duration of treatment was 59 days post HSCT) [87]. In SOT patients, prophylactic regimens with lipid formulations appear to be associated with a low incidence of IFI although further data are required [88][89][90][91]. In neutropenic patients with hematologic malignancies or solid tumors, prophylactic inhalation of aerosolized amphotericin B also demonstrated no benefit [92].…”

Section: Amphotericin Bmentioning

confidence: 97%

Aspergillus to Zygomycetes: Causes, Risk Factors, Prevention, and Treatment of Invasive Fungal Infections

Cornely

2008

Infection

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Invasive fungal infections (IFIs) are an important cause of morbidity and mortality, particularly in patients with underlying risk factors (e.g., neutropenia, cancer chemotherapy, transplantation, AIDS). Although Candida species remain a relevant cause of IFI, other organisms (particularly moulds) have become increasingly prevalent. In particular, Aspergillus species are the leading cause of mould infections although other moulds including Fusarium species and Zygomycetes are increasing in frequency, and are associated with a high mortality rate. Options available for the prevention and treatment of these infections include standard and liposomal formulations of amphotericin B, but toxicity concerns limit their use; fluconazole is effective for the prevention and treatment of candidiasis but its inactivity against moulds and increasing resistance are limiting factors. Newer azoles, particularly voriconazole and posaconazole, have an enhanced spectrum of activity that includes Candida species, Aspergillus species, Cryptococcus species, dimorphic fungi, Fusarium species, and, for posaconazole, Zygomycetes. Recent data suggest that these agents are highly effective in a variety of clinical settings. Echinocandins have good activity against Candida species and Aspergillus species but their spectrum generally does not include Fusarium species, Cryptococcus species, Trichosporon species, Zygomycetes, and dematiaceous moulds. While these agents are unlikely to exhibit crossresistance with polyenes or azoles, they must be administered intravenously. Knowledge of the pathogenesis of IFIs and the activity, efficacy, and limitations of available treatment options will allow the selection of an appropriate antifungal agent for individual patients.

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Low‐dose amphotericin for prevention of serious fungal infection following liver transplantation

Cited by 26 publications

References 23 publications

Targeted Versus Universal Antifungal Prophylaxis Among Liver Transplant Recipients

Targeted Versus Universal Antifungal Prophylaxis Among Liver Transplant Recipients

Effect of prophylaxis on fungal infection and costs for high-risk liver transplant recipients

Aspergillus to Zygomycetes: Causes, Risk Factors, Prevention, and Treatment of Invasive Fungal Infections

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