Antifungal Prophylaxis (AFP) for Patients (Pts) with Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS) Undergoing Intensive Chemotherapy: An Experience with 730 Pts.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3102-3102 ◽  
Author(s):  
Gloria Mattiuzzi ◽  
Hagop Kantarjian ◽  
Jennifer Ho ◽  
Guillermo Garcia-Manero ◽  
Jorge Cortes
Keyword(s):  
Early Intervention ◽  
Side Effects ◽  
High Risk ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Antifungal Prophylaxis ◽  
Myelogenous Leukemia ◽  
Liposomal Amphotericin B ◽  
Intensive Chemotherapy ◽  
Significant Difference

Abstract Abstract 3102 Poster Board III-39 Despite the advances in the development of antifungal agents, invasive fungal infections (IFI) remain a significant threat to patients with hematologic malignancies. The importance of early intervention for patients at high-risk for IFI has been widely discussed in several publications; however, the question of whether an early intervention such as prophylaxis is better than empiric or pre-emptive treatment still remains unanswered. Antifungal prophylaxis continues to be routinely used at MDACC for AML and HR-MDS patients. An ideal AFP regimen should be effective, safe, and uncomplicated for the patients. In the search of this ideal regimen, we have explored several options, including different type of drugs and various delivery schedules. Hereby, we report our experience since September 1997 to August 2009 with 730 AML and HR-MDS patients who received AFP for intensive chemotherapy. Proven IFI were defined as per the EORTC criteria. The following regimens were studied: Amphotericin B Lipid Complex (ABLC): 2.5 mg/kg IV three times/week; Liposomal Amphotericin B (AMBI 3TIW): 3 mg/kg IV three times/week; Fluconazole 400 mg (tab) /d + Itraconazole:200 mg (caps) /d (F + I); IV Itraconazole (IV ITRA):200 mg BID X 2 d, then 200 mg IV/d; Caspofungin (CASPO):50 mg IV /d; Voriconazole (IV VORI):400 mg IV BID x 2 d, then 300 mg IV BID; Liposomal Amphotericin B (AMBI 9/W): 9 mg/kg IV once per week; and Voriconazole (PO VORI ): 400 mg BID PO x 1 day, followed by 200 mg PO BID. Patients received ABLC, IV ITRA, F+I, AMBI 3TIW and CASPO since day 1 of IC until IC response was assessed. Pt on IV VORI, AMBI 3TIW and PO VORI started AFP within 24 hours after the last dose of IC until IC response was assessed. There were no significant differences among the pts in the 8 regimens with regards to age, gender, diagnosis, cytogenetics, performance status, presence of no fungal infection at start IC and stayed in protected environment. Table 1 shows our results. Although none of the pts receiving Voriconazole (IV or PO) developed proven IFI, all comparisons of efficacy among the AFP regimens were not significant (p= 0.291). None of the patients on AMBI 3TIW and either VORI had mold infections. There was a significant difference in the number of side effects among the 8 groups (p = 0.03). CASPO and PO VORI were the less toxic regimens. In addition, PO VORI was significantly less toxic than IV VORI (p=0.031). ABLC (N=131) AMBI 3TIW (N=69) F+I (N=67) IV ITRA (N=225) CASPO (N=106) VORI IV (N=61) AMBI 9/w (N=27) PO VORI (N=38) Breakthrough proven IFI n (%) 7(5) 3(4) 3(5) 17(8) 7(7) 0 2 (7) 0 –Yeast 2 3 1 11 3 0 1 0 –Mold 5 0 2 6 4 0 1 0 Drug-related side effects (%) 18 14 7 10 4 21 12 5 We conclude that PO VORI is safe, efficacious and easy to administer to the patients for the prevention of IFI in pts with AML and HR-MDS undergoing IC. CASPO is a safe alternative. Disclosures No relevant conflicts of interest to declare.

Voriconazole and Liposomal Amphotericin B (Ambisome) Effectively Prevent Mold Infections in Patients (pts) with Acute Myelogenous Leukemia (AML) Following Remission Induction Chemotherapy (RIC).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2773-2773 ◽  
Author(s):  
Gloria N. Mattiuzzi ◽  
Elihu H. Estey ◽  
Mike Hernandez ◽  
Maria E. Cabanillas ◽  
Francis Giles ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Myelogenous Leukemia ◽  
High Rate ◽  
Liposomal Amphotericin B ◽  
Remission Induction ◽  
Drug Discontinuation ◽  
Lipid Complex

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)

scholarly journals Efficacy of Topical Liposomal Amphotericin B versus Intralesional Meglumine Antimoniate (Glucantime) in the Treatment of Cutaneous Leishmaniasis

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Pouran Layegh ◽  
Omid Rajabi ◽  
Mahmoud Reza Jafari ◽  
Parisa Emamgholi Tabar Malekshah ◽  
Toktam Moghiman ◽  
...  
Keyword(s):  
Side Effects ◽  
Cutaneous Leishmaniasis ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Liposomal Amphotericin B ◽  
Attractive Alternative ◽  
Intention To Treat ◽  
Treatment Side Effects ◽  
Significant Difference ◽  
Clinical Responses

Background. Topical treatment of cutaneous leishmaniasis is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route. Recently liposomal formulations of amphotericin B have been increasingly used in the treatment of several types of leishmaniasis.Aims. The efficacy of a topical liposomal amphotericin B formulation was compared with intralesional glucantime in the treatment of cutaneous leishmaniasis.Methods. From 110 patients, the randomly selected 50 received a topical liposomal formulation of amphotericin B into each lesion, 3–7 drops twice daily, according to the lesion's size and for 8 weeks. The other group of 60 patients received intralesional glucantime injection of 1-2 mL once a week for the same period. The clinical responses and side effects of both groups were evaluated weekly during the treatment course.Results. Per-protocol analysis showed no statistically significant difference between the two groups (, 95% confidence interval (0.632–4.101)). Moreover, after intention-to-treat analysis, the same results were seen (, 95% (0.560–2.530)). Serious post treatment side effects were not observed in either group.Conclusions. Topical liposomal amphotericin B has the same efficacy as intralesional glucantime in the treatment of cutaneous leishmaniasis.

Low-dose liposomal amphotericin B for antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell transplantation

2020 ◽  
Author(s):  
Natalia Mendoza-Palomar ◽  
Elena Soques ◽  
María Isabel Benitez-Carabante ◽  
Miriam Gonzalez-Amores ◽  
Aurora Fernandez-Polo ◽  
...  
Keyword(s):  
High Risk ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Low Dose ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Antifungal Prophylaxis ◽  
Haematopoietic Stem Cell ◽  
Liposomal Amphotericin B ◽  
Candida Spp

Abstract Background Primary antifungal prophylaxis in paediatric allogeneic HSCT recipients is mainly based on azoles, which can have related toxicity and drug interactions. Low-dose liposomal amphotericin B (L-AmB) is an attractive intravenous alternative because of its low toxicity and lower risk of interactions. Objectives To evaluate the effectiveness and safety of L-AmB (1 mg/kg/day) for primary antifungal prophylaxis in pre-engraftment paediatric HSCT patients. Patients and methods Retrospective, observational study including all consecutive patients aged ≤18 years who underwent HSCT and received antifungal prophylaxis with intravenous L-AmB (1 mg/kg/day, from day −1 to 48 h before discharge) between January 2012 and December 2016. Results In total, 125 HSCT procedures in 118 patients were included, median age 7.2 years (IQR 4.2–11.5). Haematological malignancies were the main underlying condition (63.6%), and 109 (87.2%) were considered at high risk for invasive fungal infection (IFI). Ten patients (7.7%), all high risk, developed breakthrough IFI (three Candida spp., seven invasive mould infections) and tended to have higher overall mortality. The only statistically significant risk factor for IFI was cytomegalovirus co-infection. Adverse events, all grade I, occurred in 25 (20%), requiring L-AmB withdrawal in one case. Overall survival at 30 days was 99.2%. At study completion, one patient had died of IFI. Conclusions The incidence of breakthrough IFI was comparable to that of previous reports, with a very low rate of significant toxicity. Thus, prophylactic L-AmB may be a safe, effective option for antifungal prophylaxis in the pre-engraftment phase for children undergoing HSCT, even those at high risk.

High-dose Weekly Liposomal Amphotericin B Antifungal Prophylaxis in Patients Undergoing Liver Transplantation

2015 ◽  
Vol 99 (4) ◽  
pp. 848-854 ◽  
Author(s):  
Maddalena Giannella ◽  
Giorgio Ercolani ◽  
Francesco Cristini ◽  
Mariacristina Morelli ◽  
Michele Bartoletti ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Antifungal Prophylaxis ◽  
Liposomal Amphotericin B ◽  
High Dose

Efficacy of Early Administration of Liposomal Amphotericin B in Patients with Septic Shock: A Nationwide Observational Study

2020 ◽  
Author(s):  
Masato Tashiro ◽  
Takahiro Takazono ◽  
Yuki Ota ◽  
Tomotaro Wakamura ◽  
Akinori Takahashi ◽  
...  
Keyword(s):  
Septic Shock ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Survival Rates ◽  
Liposomal Amphotericin B ◽  
National Database ◽  
Shock Onset ◽  
Significant Difference ◽  
Nationwide Observational Study

Abstract To determine the most suitable time to initiate liposomal amphotericin B (L-AMB) treatment in patients with invasive fungal infections, patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database to determine their survival rates following septic shock onset, mortality during shock, and shock cessation period. We identified 141 patients administered L-AMB: 60 patients received treatment on the day of septic shock onset (early L-AMB group), whereas 81 patients received treatment after the onset (delayed L-AMB group). Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P=0.197; 6 weeks: 62.2% vs 44.5%, P=0.061; 12 weeks: 43.4% vs 35.0%, P=0.168, respectively). Mortality during septic shock was significantly lower in the early L-AMB group than in the delayed L-AMB group (13% vs 42%, P<0.001), with a significant difference confirmed after adjusting for confounding factors (odds ratio: 0.240, 95% confidence interval: 0.096-0.601, P=0.002). Septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0±7.0 days vs 16.5±15.4 days, P<0.001). L-AMB administration at septic shock onset could be associated with early shock cessation and decreased mortality.

Systemic Antifungal Drugs in the Hematology and Oncology Setting: A Real-Life Analysis in Consecutive Leukemia Patients of Patterns of Usage and Associated Problems,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4198-4198
Author(s):  
Barbara Metzke ◽  
Stefanie Hieke ◽  
Manfred Jung ◽  
Ralph Waesch ◽  
Monika Engelhardt
Keyword(s):  
Adverse Events ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Research Funding ◽  
Concomitant Medication ◽  
Total Bilirubin ◽  
Real Life ◽  
Antifungal Prophylaxis ◽  
Antifungal Drugs ◽  
Liposomal Amphotericin B

Abstract Abstract 4198 Introduction: Invasive fungal infections (IFI) show high morbidity and mortality rates in immunocompromised patients (pts). Systemic antifungal drugs (SAD), therefore, play an important role in the supportive care, especially in patients with acute leukemia. Over the last few years, new drugs for the prevention and treatment of IFI have been introduced. Due to the difficult diagnostics of IFI, SAD are broadly used, which represents a substantial burden for public health systems and raises issues about the optimal antifungal regimen as well as drug safety. Apart from their high costs, the use of these drugs is hampered by potential drug interactions and adverse events. We determined the extent of SAD use as well as frequency and clinical relevance of problems related to these drugs in a real-life cohort of leukemia pts at our institution. Methods: Since 2009, we prospectively analyzed SAD usage on two wards within our department. So far, the total antifungal and concomitant medication of 180 consecutive leukemia pts during antifungal prophylaxis and therapy was analyzed in terms of potential drug interactions using the electronic database Micromedex®. Drug-related adverse events were detected by regular participation on ward rounds, consultation of ward physicians and review of patients' medication charts and laboratory values. In particular, the renal and hepatic function during SAD application was closely assessed. SAD were given according to EORTC-adapted guidelines, with use of fluconazole or posaconazole as primary prophylaxis, and voriconazole, liposomal amphotericin B or caspofungin as therapeutic options. Results: Underlying diseases of the analyzed cohort included AML (n=133), ALL (n=27) and MDS (n=20). Leukemia therapy during analysis predominantly comprised chemotherapy (n=98) and allogeneic hematopoietic stem cell transplantation (n=66). Median SAD costs per analyzed hospital stay in our patient cohort were 2757€ (range: 8–34061€), with 63% of pts inducing costs higher than 1000€. SAD generated 23% of total drug costs in our hematology/oncology department in 2010, thereby ranking second position behind cytostatic agents. Within the analyzed cohort, 83/180 pts received antifungal prophylaxis only, while 97/180 pts received therapeutic regimen involving 1 (n=58), 2 (n=31), 3 (n=6) or 4 (n=2) different SAD in sequence or in combination. Due to drug-related adverse events, SAD application was discontinued or switched to a different drug in 19/180 patients (11%), primarily therapy with voriconazole (7/47, 15%) and liposomal amphotericin B (9/74, 12%). Elevations in creatinine and total bilirubin levels were most frequent during application of liposomal amphotericin B (in 17% and 33% of pts, respectively), while increased levels of alanine transaminase (ALT) were most frequent during use of posaconazole (53% of pts; predominantly CTC grade 1 and 2). Caspofungin was predominantly used in pts with liver predamage, indicated by a median baseline level of total bilirubin of 1.2 mg/dl as compared to ≤ 0.7 mg/dl for all other agents, and showed excellent tolerability. Of note, during the application of SAD, pts received a median number of 25 different concomitant drugs (range 1–54, chemotherapy not included). The proportion of pts exposed to one or more potentially interacting drug combinations involving the respective SAD was: fluconazole 95/102 (93%), caspofungin 16/20 (80%), posaconazole 37/52 (71%), liposomal amphotericin B 52/74 (70%) and voriconazole 33/47 (70%); the number of different potentially interacting drugs for each of these SAD was 17, 4, 9, 6, and 9, respectively. These 45 potentially interacting combinations were rated as moderate (n=27), major (n=17), and contraindicated (n=1) by the drug interaction software. In terms of treatment optimization, therapeutic drug monitoring of posaconazole and voriconazole proved very useful in detecting subtherapeutic levels and showed high inter-pt variability of serum levels. Conclusions: SAD are used intensively in the hematology and oncology setting and require close monitoring of pts' concomitant medication, clinical parameters and laboratory values. This ongoing project at our institution illustrates the use of these drugs in every day clinics, and valuably contributes to a safe and efficient application of this increasingly important class of drugs in our pts. Disclosures: Metzke: MSD Merck Sharp & Dohme GmbH: Research Funding. Engelhardt:MSD Merck Sharp & Dohme GmbH: Research Funding.

Successfully treated invasive pulmonary aspergillosis in a patient with diabetic ketoacidosis

Open Medicine ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. 685-688
Author(s):  
Ryo Kumagai ◽  
Gen Ohara ◽  
Shinya Sato ◽  
Kunihiko Miyazaki ◽  
Katsunori Kagohashi ◽  
...  
Keyword(s):  
Early Intervention ◽  
Invasive Aspergillosis ◽  
Diabetic Ketoacidosis ◽  
Amphotericin B ◽  
Early Treatment ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Full Recovery ◽  
Liposomal Amphotericin B ◽  
Pulmonary Aspergillosis

AbstractWe report herein a case of diabetic ketoacidosis associated with invasive aspergillosis that was successfully treated with liposomal amphotericin-B (L-AMB). Early intervention after confirming the diagnosis of invasive pulmonary aspergillosis is very important, and initiating early treatment with L-AMB can lead to a full recovery.

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