Early Empiric Antifungal Treatment of Infections in Neutropenic Patients with Hematological Malignancies Comparing Fluconazole with Amphotericin B and 5-Flucytosine

2001 ◽  
pp. 309-314
Author(s):  
G. Silling ◽  
W. Fegeler ◽  
N. Roos ◽  
M. Essink ◽  
T. Büchner
Keyword(s):  
Amphotericin B ◽  
Hematological Malignancies ◽  
Antifungal Treatment ◽  
Neutropenic Patients

Brief Report: Practicability and safety of amphotericin B deoxycholate as continuous infusion in neutropenic patients with hematological malignancies

2005 ◽  
Vol 46 (8) ◽  
pp. 1163-1167 ◽  
Author(s):  
Axel Schulenburg ◽  
Wolfgang Sperr ◽  
Werner Rabitsch ◽  
Paul Knöbl ◽  
Florian Thalhammer
Keyword(s):  
Continuous Infusion ◽  
Amphotericin B ◽  
Hematological Malignancies ◽  
Amphotericin B Deoxycholate ◽  
Neutropenic Patients

Safety and Efficacy of Caspofungin as Preventive and Empirical Antifungal Treatment of Neutropenic Allografted Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5024-5024
Author(s):  
Patrice Chevallier ◽  
Pierre Bordigoni ◽  
Thierry Lamy ◽  
Philippe Moreau ◽  
Jean-Luc Harousseau ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Therapy ◽  
Antibacterial Therapy ◽  
Conditioning Regimen ◽  
Antifungal Treatment ◽  
High Dose ◽  
Myeloablative Conditioning ◽  
Who Grade ◽  
Persistent Fever ◽  
Neutropenic Patients

Abstract Antifungal therapy is appropriate in neutropenic patients who have unexplained persistent fever, despite receipt of few days of antibacterial therapy. Conventional or liposomal amphotericin B are the preferred agents in this situation for allografted patients but toxicity or interaction with other drugs could limit their prescription. Caspofungin, the first inhibitor of fungal cell wall glucan synthesis, is the only echinocandin approved by the FDA for treatment of candidiasis. In case of suspected or documented aspergillosis infection, caspofungin is generally reserved to patients who failed to respond to amphotericin B or voriconazole. Recently, Walsh et al (ICAAC 2003) demonstrated in a randomised trial that caspofungin was comparable to liposomal amphotericine B in overall success as empirical antifungal therapy of persistently febrile neutropenic patients and was better tolerated. Here, we report our experience of caspofungin as preventive and empirical anti-fungal treatment, between November 2002 and May 2003, in 19 allografted patients with neutropenia (< 500/mm3 neutrophils) ± persistent fever despite at least 4 days of appropriate antibacterial therapy (n=12). There were 15 adult and 4 children, 11 male and 8 female. Median age was 33 years (range: 3–57). There were 6 ALL, 5 AML, 1 Myelodysplasia, 1 CML, 1 Hodgkin disease, 1 NHL, 1 myeloma, 1 aplastic anemia, 1 carcinoma and 1 Ewing sarcoma. A myeloablative conditioning regimen was used in 14 patients consisting of total body irradiation (TBI) plus high-dose chemotherapy in 9 patients and busulfan plus cyclophosphamide in 5 patients. A non myeloablative conditioning regimen was used in 5 patients. For graft-versus-host disease prophylaxis, the regimen was cyclosporin plus methotrexate in 13 patients or ATG in 6 patients. Nine patients received a bone marrow graft, 9 received granulocyte-colony-stimulating factor (G-CSF) mobilized peripheral blood stem-cells and 1 received an unrelated cord blood transplant. Twelve/19 patients have received prophylaxis with fluconazole from day 0 of the graft. Patients received caspofungin at an initial dose of 70 mg then 50 mg per day. Caspofungin was initiated within a median of 10 days after allograft (range: 0–174) including 7 patients receiving preventive caspofungin treatment at the date of aplasia. The mean duration of caspofungin therapy was 16 days (range: 3–72). Caspofungin was well tolerated and not stopped because of toxicity: WHO grade 1 and 2 hepatotoxicity occurred in 5 patients including 3 with previous hepatic abnormalities, WHO grade 1 and 2 nephrotoxicity occurred in 6 patients. No infusion reaction was observed. Only one patient developed a probable invasive bronchopulmonary aspergillosis on day 30 while receiving caspofungin. Seventeen/19 (89%) patients remain alive at least 7 days after the end of caspofungin administration without documented or suspected fungal, bacterial, or viral infection. Resolution of fever occurred in 11/12 febrile neutropenic patients in a median of 2 days (range:2–13) after starting caspofungin. We conclude that caspofungin is safe and effective as preventive and empirical antifungal treatment of neutropenic allografted patients.

Cost-Effectiveness of Antifungal Strategies in High-Risk Neutropenic Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1314-1314 ◽  
Author(s):  
Michael Schwarzinger ◽  
Sylvain Baillot ◽  
Celine Beauchamp ◽  
Sebastien Maury ◽  
C. écile Pautas ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
High Risk ◽  
Incremental Cost ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
Hematological Malignancies ◽  
Cost Effective ◽  
Antifungal Drugs ◽  
Hospitalization Costs ◽  
Neutropenic Patients

Abstract Background: Invasive fungal infections (IFIs) incur significant morbidity and mortality among neutropenic patients with hematological malignancies. Prevention and early antifungal treatment include prophylaxis where antifungal agent is started along with neutropenia; empirical therapy where antifungal agent is initiated in persistently febrile patients at least four days after neutropenia onset; preemptive therapy where antifungal agent is initiated later for a suspected IFI based on clinical symptoms, lung imaging, or biological markers. Without data from clinical trials comparing antifungal strategies, determining an optimal antifungal strategy for these patients is challenging. Objective: To determine the cost-effectiveness of all possible antifungal strategies. Target Population: Adult patients with hematological malignancies in induction chemotherapy at high risk for IFIs. Interventions: Prophylaxis with either fluconazole or posaconazole, empirical strategy, and preemptive strategy with fist-line antifungal therapy being amphotericin B, liposomal amphotericin B or caspofungin (Table). Design: Cost-effectiveness decision model. The study cohort encountered seven successive chance nodes during hospital stay: having fever; in those having fever, IFI incidence; Aspergillus or Candida species among IFI; admission in intensive care unit; dying from IFI or underlying hematological malignancy; in patients alive, having severe nephrotoxicity as defined by a twofold increase in baseline serum creatinin; dying from severe nephrotoxicity. Antifungal strategies modified the probabilities of IFI and severe nephrotoxicity that depended on both the duration and the type of antifungal drugs administered. Data Sources: PREVERT trial1, effectiveness data published to December 2007, probabilities of ICU admission and in-hospital mortality according to the occurrence of IFI in the French DRG database, life expectancy of French patients with acute myeloid leukemia, and actual French hospitalization costs (2007 euros). Time Horizon: Lifetime. Perspective: Societal. Outcome Measures: Incremental cost (euros) per discounted life-year saved averaged from 100 samples of 1000 patients (second-order probabilistic Monte Carlo simulations). Results (Table): Fluconazole prophylaxis followed by ampho-B treatment was the cheapest antifungal strategy. Posaconazole prophylaxis followed by ampho-B was nearly cost-effective (59,610 € per discounted year of life gained). Other strategies were either dominated or beyond usual societal thresholds of what may be worth it. Similar results were found in sensitivity analyses among plausible ranges. Conclusions: As compared to previous studies showing that new antifungal drugs were cost-effective within a single strategy, empirical and preemptive antifungal strategies were dominated by prophylaxis strategies. Table: Incremental cost-effectiveness ratio of antifungal strategies in high-risk neutropenic patients Total cost (2007 euros) Years of life gained ICER IFI (%) Aspergillus (%) Nephro-toxicity (%) Antifungals’ cost (2007 euros) Fluconazole then amphoB 35606 2.3448 -- 3.81% 2.61% 4.22% 909 Fluconazole then L-amphoB 36025 2.3457 (extended dominance) 3.81% 2.61% 3.67% 1430 Empirical amphoB 36033 2.3433 (dominated) 3.38% 2.3% 5.98% 1914 Posaconazole then amphoB 36065 2.3525 59,610 € 1.2% 0.81% 3.67% 2646 Preemptif amphoB 36160 2.3449 (dominated) 3.89% 2.67% 4.42% 1247 Posaconazole then L-amphoB 36389 2.3532 462,857 € 1.2% 0.81% 3.21% 3055 Fluconazole then Caspo 36557 2.3459 (dominated) 3.81% 2.61% 3.53% 1985 Preemptif L-amphoB 36616 2.3455 (dominated) 3.89% 2.67% 3.84% 1809 Posaconazole then Caspo 36828 2.3533 4,390,000 € 1.2% 0.81% 3.13% 3509 Empirical L-amphoB 37308 2.3462 (dominated) 3.38% 2.3% 4.39% 3239 Preemptif Caspo 37346 2.3458 (dominated) 3.89% 2.67% 3.55% 2597 Empirical Caspo 39123 2.3473 (dominated) 3.38% 2.3% 3.47% 5080

scholarly journals Continuous infusion of amphotericin B: preliminary experience at Faculdade de Medicina da Fundação ABC

2005 ◽  
Vol 123 (5) ◽  
pp. 219-222 ◽  
Author(s):  
Roberto Palermo Uehara ◽  
Victor Hugo Lara de Sá ◽  
Érika Tae Koshimura ◽  
Fernanda Vilas Boas Prudente ◽  
Luciana Tomanik Cardozo de Mello Tucunduva ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Amphotericin B ◽  
Hematological Malignancies ◽  
Efficacy And Safety ◽  
Median Dose ◽  
Liposomal Formulations ◽  
Amphotericin B Deoxycholate ◽  
Neutropenic Patients ◽  
Intravenous Amphotericin ◽  
De Medicina

CONTEXT AND OBJECTIVE: Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy. DESIGN AND SETTING: Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André. METHODS: From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D. RESULTS: The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles. CONCLUSIONS: Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug.

scholarly journals Antibiotic Rotation for Febrile Neutropenic Patients with Hematological Malignancies: Clinical Significance of Antibiotic Heterogeneity

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e54190 ◽  
Author(s):  
Yong Chong ◽  
Shinji Shimoda ◽  
Hiroko Yakushiji ◽  
Yoshikiyo Ito ◽  
Toshihiro Miyamoto ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Hematological Malignancies ◽  
Neutropenic Patients

The efficacy of itraconazole against systemic fungal infections in neutropenic patients: A randomised comparative study with amphotericin B

1991 ◽  
Vol 22 (1) ◽  
pp. 45-52 ◽  
Author(s):  
J.W. van't Wout ◽  
I. Novakova ◽  
C.A.H. Verhagen ◽  
W.E. Fibbe ◽  
B.E. de Pauw ◽  
...  
Keyword(s):  
Comparative Study ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Neutropenic Patients
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