Antifungal prophylaxis with liposomal amphotericin B and caspofungin in high-risk patients after liver transplantation: impact on fungal infections and immune system

2015 ◽  
Vol 48 (2) ◽  
pp. 161-166 ◽  
Author(s):  
A. Perrella ◽  
C. Esposito ◽  
G. Amato ◽  
O. Perrella ◽  
C. Migliaccio ◽  
...  
Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3971-3971
Author(s):  
Roman Crazzolara ◽  
Julia Hutter ◽  
Josef Fritz ◽  
Christina Salvador ◽  
Cornelia Lass-Flörl ◽  
...  

Abstract BACKGROUND: Prophylaxis of invasive fungal infections in children treated for malignant hematologic disease has traditionally been based on the widespread use of fluconazole. With the awareness of increasing rates of invasive mould infections, new agents have been developed and offered to patients at highest risk. METHODS: We compared the tolerance and outcome of different antifungal prophylaxis in 198 childhood patients treated for acute myeloid and lymphoblastic leukemia in a pediatric cancer center. Until 2011 antifungal prophylaxis with fluconazole was offered to all patients, resulting in 15.2-19.4% of invasive mould infections. As the burden of fungal infections was restricted to high risk patients only (i.e. acute myeloid leukemia, leukemia relapse, high risk acute lymphoblastic leukemia and patients after stem cell transplant) and no infection with candida was registered, antifungal prophylaxis was replaced with liposomal amphotericin and offered to this particular patient group. RESULTS: Liposomal amphotericin was well tolerated; there was no occurrence of infusion-related reaction and/or glomerular-associated nephrotoxicity. The development of vincristine-induced neurotoxicity was significantly reduced, as stool frequency was increased up to 38% in patients treated with liposomal amphotericin (p = 0.024). Importantly, there was a marked shift in the percentage of patients with severe constipation (15.5% versus 4.2%, fluconazole versus liposomal amphotericin respectively, p = 0.010). Notably, with limitation of prophylactic treatment to high risk patients a major group of patients did not receive any antifungal prophylaxis (48.81%) and most importantly, the occurrence of invasive fungal infection was completely prevented (p = 0.021). In comparison, 10 patients in the fluconazole group developed proven invasive pulmonary infections. Of these, 6 patients developed disseminated disease, and 4 patients died. Aspergillus was isolated in 40% and rhizopus in 30% of biopsy specimens. CONCLUSION: Polyene prophylaxis offers effective antifungal activity with improved tolerability compared to older agents. The potential impact of this treatment should be included in current prophylaxis guidelines of antileukemic treatment. Disclosures No relevant conflicts of interest to declare.


2015 ◽  
Vol 99 (4) ◽  
pp. 848-854 ◽  
Author(s):  
Maddalena Giannella ◽  
Giorgio Ercolani ◽  
Francesco Cristini ◽  
Mariacristina Morelli ◽  
Michele Bartoletti ◽  
...  

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4541-4541
Author(s):  
Giuseppe Irrera ◽  
Messina Giuseppe ◽  
Giuseppe Console ◽  
Massimo Martino ◽  
Cuzzola Maria ◽  
...  

Abstract Abstract 4541 Introduction: Limited data demonstrate to what extent preventing fungal exposures is effective in preventing infection and disease. Further studies are needed to determine the optimal duration of fluconazole prophylaxis in allogeneic recipients to prevent invasive disease with fluconazole-susceptible Candida species during neutropenia. Oral, nonabsorbable antifungal drugs might reduce superficial colonization and control local mucosal candidiasis, but have not been demonstrated to reduce invasive candidiasis. Anti-fungal prophylaxis is recommended in a subpopulation of autologous recipients with underlying hematologic malignancies with prolonged neutropenia and mucosal damage. Methods: This is a retrospective study of 1007 SCT performed in our center between 1992 and 2009 in 809 consecutive patients, irrespective of diagnosis. HEPA filter and environmental monitoring (air, water, surfaces) are attributes of our transplant center. Results: The main characteristics of the patients are reported in Table 1. Systemic prophylaxis was used according to the guidelines (Table 2): fluconazole in the nineties, then itraconazole and from 2004 was either abolished or substituted with non-adsorbable prophylaxis in transplants with standard risk. Secondary prophylaxis was prescribed for high risk patients (with infectious fungal history, suggestive iconography, positive fungal biomarker). In 17 years our Center has never been colonized by mould. Only 3 probable aspergillosis infections and 4 proven fungal infections (fusarium, mucor and 2 aspergillosis) were diagnosed, all in allogeneic patients (2 haplotipical, 1 singenic, 1 sibiling, 1 MUD and 2 mismatched), resulting in death in all cases. No infection was documented in autologous setting, while the infection rate in allogenic setting was 3.6% with an incidence rate of 1.1 infection per 10000 transplants/year. These results are significantly lower than published reports. Conclusion: Systemic antifungal prophylaxis should not be performed in autologous SCT patients. The abuse of systemic prophylaxis targeting yeasts has influenced the change of epidemiology in the transplant setting with prevalence of mould infections. The identification of high risk patients is useful to select patients for systemic antifungal or secondary prophylaxis to reducing overtreatment, incidence of resistant strains and costs. Disclosures: No relevant conflicts of interest to declare.


2006 ◽  
Vol 55 (10) ◽  
pp. 1357-1365 ◽  
Author(s):  
Michael Ellis ◽  
Chris Frampton ◽  
Jose Joseph ◽  
Hussain Alizadeh ◽  
Jorgen Kristensen ◽  
...  

In a clinical non-trial setting, the efficacy and safety of caspofungin was compared with liposomal amphotericin B for the management of febrile neutropenia or invasive fungal infections in 73 episodes in patients with haematological malignancy. There were fewer episodes of drug toxicity with caspofungin than liposomal amphotericin B (58.3 vs 83.7 %, P=0.02). The favourable response rate for episodes of febrile neutropenia treated with caspofungin or liposomal amphotericin B was similar at 37.5 and 53.8 %, respectively, but more breakthrough fungal infections occurred with caspofungin than with liposomal amphotericin B (33.3 vs 0 %, P<0.05) in these patients who did not receive antifungal prophylaxis. None of four episodes of candidaemia or hepatosplenic candidiasis responded to caspofungin compared with three of four episodes treated with liposomal amphotericin B. Mortality was significantly higher with caspofungin treatment compared with liposomal amphotericin B (6/24 vs 2/49, P=0.01), mainly due to an excess of fungal infections (P=0.04). Caspofungin treatment was a significant independent predictor of mortality [odds ratio=7.6 (95 % confidence interval 1.2–45.5)] when sepsis severity, prolonged neutropenia and length of antifungal therapy were considered in a multiple logistic regression model. In clinical practice, there is a suggestion that caspofungin may not be as effective as liposomal amphotericin B in preventing breakthrough invasive fungal infections in febrile neutropenia or in preventing fungus-related deaths. Because of the potential biases in this observational study, these preliminary findings should be interpreted with caution and clarified with a larger cohort of patients.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2773-2773 ◽  
Author(s):  
Gloria N. Mattiuzzi ◽  
Elihu H. Estey ◽  
Mike Hernandez ◽  
Maria E. Cabanillas ◽  
Francis Giles ◽  
...  

Abstract Invasive fungal infections (IFI) are a frequent cause of morbidity and death in pts with AML and high-risk myelodysplastic syndrome (HR-MDS). Because early diagnosis of IFI is difficult, antifungal prophylaxis (AFP) including mold-active agents has become an important strategy to reduce morbidity and mortality in this patient population and is routinely used at MDACC for AML and HR-MDS pts undergoing RIC. We retrospectively compared the efficacy and safety of 6 AFP regimens (Sept 97- July 04) among 659 evaluable pts with newly diagnosed AML and HR-MDS who received RIC and had been enrolled in our prospective AFP trials. See regimens listed in Table below. There were no significant differences among the 6 regimens with regard to key baseline characteristics (age, gender, diagnosis, cytogenetics, type of RIC, Zubrod PS, WBC count, non-fungal infection and protected environment) and median days of AFP. 37 pts (5.6%) developed IFI (yeast 3 %; mold 2.6%). No mold infections were observed among pts randomized to AMBI or VORI. With the exception of VORI, which was significantly more effective than IV ITRA (p =0.03), all comparisons of efficacy among the AFP regimens were not significant. Drug discontinuation was the highest with IV VORI (21%) and ABLC (18%). VORI was more toxic than IV ITRA, Caspo, and F+I (p=0.023, 0.001 and 0.031 respectively). VORI toxicity was reversible and consisted of visual and/or auditory hallucinations and elevation in serum bilirubin. There was a trend toward developing VORI toxicity if baseline bilirubin levels were elevated (OR=4.9; p=0.10). We conclude that the rate of IFI in AML and HR-MDS pts undergoing RIC given mold-active AFP is 5.6 %. VORI and AMBI effectively prevented mold infections. VORI was more effective that IV ITRA but was associated with a high rate of reversible drug-related adverse events. ABLC (n=131) AMBI (n=69) F+I (n=67) IV ITRA (n=225) CASPO (n=106) VORI (n=61) ABLC: Amphotericin B Lipid Complex: 2.5 mg/kg IV three times/week; AMBI: Liposomal Amphotericin B: 3 mg/kg IV three times/week; F+I: Fluconazole: 400 mg (tab)/d + Itraconazole: 200 mg (caps)/d; IV ITRA: IV itraconazole: 200 mg BID X 2 d, then 200 mg IV/d; CASPO: Caspofungin: 50 mg IV/d; VORI: Voriconazole: 400 mg IV BID x 2 d, then 300 mg IV BID. Median age, years (range) 65(21–87) 63(36–83) 57(19–84) 62(17–89) 65(22–82) 59(23–79) Zubrod ≤ 2 (%) 127(97) 69(100) 65(97) 214(95) 101(95) 61(100) Median days AFP (range) 17(3–32) 14(3–28) 16(3–44) 20(3–41) 21(3–38) 21(3–34) Breakthrough IFI (%) 7(5) 3(4) 3(5) 17(8) 7(7) 0     Yeast (%) 2(2) 3(4) 1(1) 11(5) 3(3) 0     Mold (%) 5(4) 0 2(3) 6(3) 4(4) 0 Drug-related AFP DC (%) 24(18) 10(14) 5(7) 23(10) 4(4) 13(21)


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