Parenteral 5-Fluorocytosine for Candidiasis

1979 ◽  
Vol 13 (2) ◽  
pp. 72-75 ◽  
Author(s):  
S. M. MacLeod ◽  
T. Y. Ti ◽  
R. B. Williams ◽  
E. M. Sellers
Keyword(s):  
North America ◽  
Adverse Effects ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Invasive Fungal Infection ◽  
Invasive Candidiasis ◽  
Antifungal Drug ◽  
Investigational Drug ◽  
Clinically Significant ◽  
Parenteral Preparation

5-Fluorocytosine (5-FC), a systemic antifungal drug, has recently been approved for oral use in North America; however, the parenteral preparation remains an investigational drug. This report describes the use of parenteral 5-FC in nine patients with candidiasis. Six patients had invasive fungal infection and three patients had colonization. Eight patients received 5-FC intravenously and one received an intraperitoneal infusion. Of the six patients with invasive candidiasis, four received concurrent amphotericin B therapy. Candidiasis was cleared in eight of the nine patients. One patient died during therapy with combined 5-FC and amphotericin B. No clinically significant adverse effects of parenteral 5-FC were observed; however, two patients showed a transient increase in SGOT.

scholarly journals Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency

Blood ◽  
2013 ◽  
Vol 121 (13) ◽  
pp. 2385-2392 ◽  
Author(s):  
Agata Drewniak ◽  
Roel P. Gazendam ◽  
Anton T. J. Tool ◽  
Michel van Houdt ◽  
Machiel H. Jansen ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Invasive Candidiasis ◽  
Key Points

Key Points Human CARD9 deficiency is characterized by a selective neutrophil killing defect, resulting in invasive candidiasis.

Empiric Antifungal Therapy with Amphotericin B in the Era of Fluconazole Prophylaxis: a Cohort Study in Adults with Acute Myeloid Leukemia Treated within An Institutional Antifungal Policy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1390-1390
Author(s):  
Anita Adams ◽  
Tamana Hafid ◽  
Kari Kolm ◽  
Jolanta Jeziorowska ◽  
Deborah C Marcellus ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Induction Chemotherapy ◽  
Antifungal Therapy ◽  
Empiric Therapy ◽  
Best Supportive Care ◽  
Antifungal Prophylaxis ◽  
Second Line ◽  
Fluconazole Prophylaxis

Abstract Abstract 1390 Poster Board I-412 Purpose: To determine whether fluconazole prophylaxis was effective in decreasing the need for parenteral empiric antifungal therapy in patients with acute myeloid leukemia (AML) and persistent febrile neutropenia or suspected fungal infection at our center. Background: Prophylaxis with fluconazole in patients with severe chemotherapy-related neutropenia has been found to be beneficial in decreasing the need for parenteral antifungal therapy, and preventing superficial and invasive fungal infections and fungal infection-related mortality (Bow et al., Cancer 2002;94:3230-3246). Methods: The records of all patients at our hospital who presented with AML from January 1999 to July 2009 were reviewed retrospectively. As of September 2005 we adopted an institutional antifungal policy consisting of routine antifungal prophylaxis with fluconazole followed by amphotericin B as the first line parenteral agent in the event of persistent fever despite broad spectrum antibiotics or suspected fungal infection. The policy included criteria for switching from amphotericin B to a second line agent (caspofungin) for continued empiric therapy or another agent depending on clinical or laboratory data or suspicion of a particular pathogen. Explicit criteria were also developed for switching to a second line agent including baseline renal function or change in renal function while receiving amphotericin B or other adverse effects such as significant infusion reactions or electrolyte disturbances. Fluconazole was given at a dose of 400 mg daily starting with induction chemotherapy and continued until blood count recovery or switch to parenteral antifungal agent. Results: We identified a total of 170 patients with a median age of 61 years (range 18-89 years), 53 % were female and the median follow-up time was 187 days (range 2-2549 days). Baseline cytogenetics grouped patients into poor risk (40%), standard risk (39%) and favorable risk (10%) categories, with 11% unknown or inconclusive. Two-thirds of patients had de-novo AML. Twenty-four percent of patients did not receive induction chemotherapy and were treated with best supportive care, leaving 130 patients who received induction chemotherapy. Overall median survival for chemotherapy treated patients was 409 days, compared with 44 days for patients treated with best supportive care. The majority of patients (77%) who received chemotherapy were treated with standard induction consisting of 3 days of an anthracycline and 7-10 days of continuous infusion cytarabine. Of the patients treated with induction chemotherapy, 65% received prophylaxis with fluconazole and 32% did not, the remainder received prophylaxis with other antifungal agents. The use of prophylactic fluconazole coincided with implementation of our antifungal policy. Of patients who were treated with fluconazole prophylaxis, 62% required parenteral antifungal therapy and 38% did not. Of patients who did not receive fluconazole prophylaxis 56% required parenteral antifungals and 44% did not. These differences relating to receiving fluconazole prophylaxis were not statistically significantly different. For those patients requiring empiric antifungal therapy, they received a median of 18 days of fluconazole (range 3-156 days). Of the 56 patients who were treated with amphotericin B as empiric therapy, 59% were changed to another agent due to renal effects (42%), fever (27%) or other adverse effects (21%). Switching off amphotericin B occurred after a median of 7.5 days (range 0-59 days). Fifty-six percent of patients received caspofungin as the second line agent while the policy was in effect. Conclusion: Based on our retrospective analysis of the practical use of antifungal prophylaxis within our institutional antifungal policy, fluconazole prophylaxis did not decrease the need for empiric parenteral antifungal therapy. The majority of patients treated with empiric amphotericin B were switched to a second line agent, mostly due to intolerance or adverse effects. Disclosures: No relevant conflicts of interest to declare.

Haemopoietic Cell Transplantation of Patients with a History of Deep or Invasive Fungal Infection during Prophylaxis with Liposomal Amphotericin B

2005 ◽  
Vol 113 (2) ◽  
pp. 104-108 ◽  
Author(s):  
William H. Krüger ◽  
Bettina Rüssmann ◽  
Maike de Wit ◽  
Nicolaus Kröger ◽  
Helmut Renges ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Amphotericin B ◽  
Cell Transplantation ◽  
Invasive Fungal Infection ◽  
Liposomal Amphotericin ◽  
Liposomal Amphotericin B ◽  
History Of

scholarly journals Adaptation to Fluconazole via Aneuploidy Enables Cross-Adaptation to Amphotericin B and Flucytosine in Cryptococcus neoformans

2021 ◽  
Author(s):  
Feng Yang ◽  
Vladimir Gritsenko ◽  
Hui Lu ◽  
Cheng Zhen ◽  
Lu Gao ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Invasive Fungal Infection ◽  
Cryptococcus Gattii ◽  
Content Type ◽  
Therapeutic Drugs ◽  
Cross Adaptation ◽  
Pyrimidine Analogues ◽  
Globally Distributed

Cryptococcosis is a globally distributed invasive fungal infection caused by infections with Cryptococcus neoformans or Cryptococcus gattii . Only three classes of therapeutic drugs are clinically available for treating cryptococcosis: polyenes (amphotericin B), azoles (fluconazole), and pyrimidine analogues (flucytosine).

scholarly journals Invasive Fungal Infection in the Setting of Peripheral Blood Non-Manipulated Haploidentical Stem Cell Transplantation with Postransplant Cyclophosphamide

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5710-5710
Author(s):  
Nieves Dorado ◽  
Gillen Oarbeascoa ◽  
Miguel Argüello ◽  
Pascual Balsalobre ◽  
David Serrano ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Cell Transplantation ◽  
Invasive Fungal Infection ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Pulmonary Involvement

Abstract Introduction: Invasive Fungal Infection (IFI) is a serious complication after allogeneic stem cell transplantation (alloSCT). Its incidence and outcome are not well characterized in the setting of peripheral blood, non-manipulated haploidentical stem cell transplantation with postransplant cyclophosphamide (HaploSCT). The aim of the study is to analyze our experience among patients who underwent HaploSCT at our institution and developed an IFI, in order to identify the incidence, risk factors and its impact in survival. Materials and methods: One hundred and thirty-three patients underwent peripheral blood HaploSCT with postransplant cyclophosphamide at our institution between 2011 and 2017. IFI was classified according to the EORTC definitions. Proven and probable IFI were included. Results: Patients´ characteristics are shown in Table 1. Patients received primary antifungal prophylaxis with micafungin from the day before stem cell infusion, during admission and until neutrophil engraftment was stablished. Patients on steroid treatment due to GVHD received prophylaxis with micafungin or posaconazole. Twenty-three episodes of IFI were observed in 20 patients, 10 proven and 13 probable, with a cumulative incidence of IFI of 15% at 500 days. Most commonly isolated organism was Aspergillus spp (5 cases), followed by Candida spp (4 cases: 1 C. kruseii and 3 C. parapsilosis) and Fusarium spp (2 cases). Additionally we observed some isolated cases of Inonotus spp,Mucor spp and Trichosporon Ashii. Pulmonary involvement was the most frequent presentation (11 cases), followed by fungemia (5 cases, 4 Candida and 1 Trichosporon Ashii) and skin-pulmonary involvement (2 cases). Thirteen cases were diagnosed early, in the pre-engraftment period, 5 just after the engraftment and 5 cases developed later. Among patients with late occurrence of IFI, median time of IFI was 220 days, and all of them were associated with GVHD (3 grade III-IV acute GVHD and 2 moderate/severe chronic GVHD). IFI outcome was favorable in 14 out of the 23 documented IFI, with antifungal therapy. Treatment chosen was liposomal amphotericin B in 7 cases, voriconazole in 5 and combined treatment (with amphotericin B and azole) in 6. Death related to IFI was documented in 7 out of the 20 patients, with an IFI mortality cumulative incidence of 6.4%. Prior transplant (OR 4.5, p <0.01) and especially alloHSCT were associated to IFI development (OR 8.2, p <0.01). We did not find any other risk factor associated to IFI, like time of engraftment, disease, conditioning regimen, sequential regimen, grades II-IV GVHD or severe/moderate chronic GVHD. Conclusions: In our experience, cumulative incidence of IFI in the setting of HaploSCT was similar than the one observed in other studies with alloSCT. Mortality associated to IFI in the whole cohort was low (6.4 %). The most significant factor related to IFI development was having received a previous transplant, especially alloSCT. Therefore, this high risk population should be closely monitored and could benefit from prophylaxis with azoles. Disclosures No relevant conflicts of interest to declare.

scholarly journals Secondary antifungal prophylaxis in allogeneic hematopoietic stem cell transplant recipients with invasive fungal infection

2018 ◽  
Vol 12 (09) ◽  
pp. 799-805
Author(s):  
Mehmet S Pepeler ◽  
Şeyma Yildiz ◽  
Zeynep A Yegin ◽  
Zübeyde N Özkurt ◽  
Özlem G Tunçcan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Hematopoietic Stem Cell ◽  
Invasive Fungal Infection ◽  
Previous History ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Stem ◽  
History Of

Introduction: Invasive fungal infection (IFI) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. A previous history of IFI is not an absolute contraindication for allo-HSCT, particularly in the era of secondary antifungal prophylaxis (SAP). Prompt diagnosis and therapy are essential for HSCT outcome. Methodology: The charts of 58 allo-HSCT recipients [median age:29.5 (16-62); M/F:41/17] who had a previous history of IFI were retrospectively reviewed. Results: Possible IFI was demonstrated in 32 (55.2%), probable in 13 (22.4%) and proven in 13 patients (22.4%). All patients received SAP [liposomal amphoterisin B (n ꞊ 35), voriconazole (n ꞊ 17), caspofungin (n ꞊ 2), posaconazole (n ꞊ 1), combination therapy (n = 3)] which was started on the first day of the conditioning regimen. Treatment success was better in the voriconazole group when compared to the amphotericin B arm (100% vs 69.2%; p = 0.029). Development of breakthrough IFI was more frequent in patients on amphotericin B prophylaxis (42.4% vs 23.1%; p = 0.036). Clinical and radiological response were achieved in 13 of 18 patients (72.2%) who developed breakthrough infection. Overall survival of the study population was 13.5% at a median follow-up of 154 (7-3285) days. Fungal mortality was found to be 23%. Overall survival was better in the voriconazole arm, without statistical significance (90% vs 65.8%, p > 0.05). Conclusions: Secondary antifungal prophylaxis is considered to be an indispensible strategy in patients with pre-HSCT IFI history. Voriconazole seems to be a relatively better alternative despite an underlying necessity of larger prospective trials.

scholarly journals Amphotericin B, the Wonder of Today’s Pharmacology Science: Persisting Usage for More Than Seven Decades

2020 ◽  
Author(s):  
Falah Hasan Obayes AL-Khikani
Keyword(s):  
Adverse Effects ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Wide Spectrum ◽  
Antifungal Drugs ◽  
Systemic Fungal Infection

Background: Despite several available topical and systemic antifungal drugs for the treatment of fungal infections, Amphotericin B (AmB) is still one of the most common first-line choices in treating systemic fungal infection for more than seven decades after its discovery.  Objectives: Amphotericin B which belongs to the polyene group has a wide spectrum of in vitro and in vivo antifungal activity. Its mechanism of antifungal action is characterized by creating a pore in the fungal plasma membrane leading to cell death. Methods: In addition to the old formula of deoxycholate-Amphotericin B (D-AmB), three lipid formulas have been developed to reduce the adverse effects of conventional AmB (D-AmB) in the human body and increase its therapeutic efficacy. All of the known available formulas of AmB are administrated via intravenous injection to treat severe systemic fungal infections, while the development of the topical formula of AmB is still under preliminary research. Numerous pharmaceutical formulas of systemic and topical applications with clinical uses of AmB in just humans, not in vitro or animals model, against various fungal infections are discussed in this review. Topical AmB formulas are a promising way to develop effective management and to reduce the adverse effects of intravenous formulas of AmB without laboratory monitoring. Results: The wonderful pharmacological properties of AmB with its prolonged use for about seven decades may help researchers to apply its unique features on other various antimicrobial agents by more understanding about the AmB mechanisms of actions. Conclusion: Amphotericin B is widely used intravenously for the treatment of systemic fungal infection, while the topical formula of AmB is still under experimental study. 

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