Itraconazole For Antifungal Prophylaxis Research Articles

Comparing posaconazole and itraconazole for antifungal prophylaxis in critically ill lung transplant recipients: Efficacy and plasma concentrations.

Posaconazole and itraconazole are commonly used for systemic antifungal prophylaxis after lung transplantation. The aim of this study on critically ill lung transplant recipients was to assess the rate of adequate plasma concentrations and the frequency of fungal-induced transitions from antifungal prophylaxis to therapy after the administration of either posaconazole or itraconazole for systemic prophylaxis. Critically ill lung transplant recipients with postoperative posaconazole or itraconazole prophylaxis and therapeutic drug monitoring from February 2016 to November 2019 were retrospectively included in the study. Positive fungal cultures or Aspergillus antigen tests resulting in a transition from antifungal prophylaxis to therapy were analyzed from the first day of prophylaxis until 7days after the last sample for each patient. Adequate plasma concentrations were defined as ≥500µg/L for itraconazole and ≥700µg/L for posaconazole. Two hundred seventy-five samples from 73 patients were included in the analysis. Overall, 60% of the posaconazole and 55% of the itraconazole concentrations were subtherapeutic. Administration of posaconazole suspension resulted significantly (P<.01) more often in subtherapeutic concentrations than tablets (68% vs 10%). Patients treated with posaconazole showed less positive fungal records resulting in a transition from prophylaxis to therapy than patients treated with itraconazole (10% vs 33%, P-value: .029). The detection of a fungal pathogen was not associated with the measured plasma concentrations or the achievement of the target concentrations. Our findings suggest that posaconazole should be used instead of itraconazole for systemic prophylaxis in critically ill lung transplant recipients.

Bridging antifungal prophylaxis with micafungin in hematopoietic stem cell transplantation: a retrospective analysis

ABSTRACT Objectives: The objective of the study was to assess the tolerability and effectiveness of micafungin prophylaxis during the neutropenic phase in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Methods We conducted a retrospective study of 73 consecutive adults receiving antifungal prophylaxis with micafungin bridged to voriconazole/itraconazole in our center from July 2013 to March 2018. Clinical and transplant-related demographics and data on fungal infection post-transplant were collected. Results Micafungin was effective in 71 (97.3%) leukopenic patients. The fungal-free survival was 91.8%, 80.6%, and 77.6% respectively at 30, 60, and 100 days after HSCT. All patients had no micafungin-related adverse events. Conclusions The utility of micafungin bridged to voriconazole/ itraconazole for antifungal prophylaxis after HSCT is beneficial.

Voriconazole Vs. Itraconazole for Antifungal Prophylaxis in Patients with GVHD: A Randomized Trial

Voriconazole Vs. Itraconazole for Antifungal Prophylaxis in Patients with GVHD: A Randomized Trial Yoshiki Hayashi , Yoshinobu Kanda , Hirohisa Nakamae , Heiwa Kanamori , Kazuteru Ohashi , Michihiro Hidaka , Shingo Yano , Kazuo Hatanaka , Akio Kohno , Yukiyoshi Moriuchi , Hiroatsu Ago , Takuya Yamashita , Tohru Takata , Minoru Yoshida , Masayuki Hino , Takuhiro Yamaguchi , Takahiro Fukuda . 1 Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan; Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan; 3 Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; 4 Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan; 5 Division of Hematology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; 6 Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan; Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan; 8 Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan; 9 Department of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan; 10 Department of Hematology, Sasebo City General Hospital, Sasebo, Japan; Department of Hematology and Oncology, Shimane Prefectural Central Hospital, Shimane, Japan; 12 Department of Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan; 13 Department of Infection Control, Fukuoka University Hospital, Fukuoka, Japan; 14 Fourth Department of Internal Medicine, Teikyo University School of Medicine, Kawasaki, Japan; 15 Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan

Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta‐analysis of randomised‐controlled trials

Fluconazole and itraconazole are used as antifungal prophylaxis in neutropenic patients with haematological malignancies. A meta-analysis of randomised-controlled trials (RCTs) was performed in order to compare their safety and effectiveness in this population. Data were obtained from PubMed, Current Contents, Cochrane Central Register for Controlled Trials and references from relevant articles. Five RCTs were included in the analysis. Publication bias and statistically significant heterogeneity was not observed among the analysed studies. Fewer patients were withdrawn due to the development of adverse effects associated with fluconazole when compared with itraconazole [odds ratio (OR) = 0.27, 95% confidence interval (CI): 0.18-0.41]. On the contrary, prophylactic use of fluconazole resulted in significantly more fungal infections (documented and suspected infections combined, OR = 1.62, 95% CI: 1.06-2.48). There were no statistically significant differences regarding documented fungal infections (OR = 1.51, 95% CI: 0.97-2.35), invasive fungal infections (OR = 1.44, 95% CI: 0.96-2.17), overall mortality (OR = 0.89, 95% CI: 0.63-1.24) and mortality attributed by the authors to fungal infections (OR = 1.30, 95% CI: 0.75-2.25) between the two medications. These data suggest that, even though itraconazole is more effective than fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies, the development of more adverse effects may limit its use.

Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies.

To report the initial data on allogeneic peripheral blood stem cell transplantation for haematological malignancies in Pakistan. A single centre descriptive study. Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre from September 1999 to June 2004. Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10(9)/l was 10 days (range 8 - 12 days) and platelet count of > 20 x 10(9)/l was 14 days (12-17 days). Acute graft versus host disease ( aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. Haematopoietic stem cell transplant programme can be developed in a developed country setting. Post transplant complications are similar to what have been reported in the developed countries. In endemic areas malaria could prove to be fatal if not recognised and treated early.

Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients.

Efficacy of antifungal prophylaxis has not yet been convincingly proven in numerous trials of various antifungals. New evidence and the anti-Aspergillus efficacy of itraconazole prompted a new look at the data for the prevention of invasive fungal infections. Randomized, controlled studies with itraconazole for antifungal prophylaxis in neutropenic patients with hematologic malignancies were identified from electronic databases and hand searching. Thirteen randomized trials included 3,597 patients who were assessable for invasive fungal infections. Itraconazole reduced the incidence of invasive fungal infection (mean relative risk reduction, 40% +/- 13%; P =.002), the incidence of invasive yeast infections (mean, 53% +/- 19%; P =.004) and the mortality from invasive fungal infections (mean, 35% +/- 17%; P =.04) significantly. The incidence of invasive Aspergillus infections was only reduced in trials using the itraconazole cyclodextrine solution (mean, 48% +/- 21%; P =.02) and not itraconazole capsules (mean, 75% +/- 73% increase; P =.3). The overall mortality was not changed. Adverse effects were rare, hypokalemia was noted in three studies, and a higher rate of drug discontinuation was found in trials that compared itraconazole cyclodextrine solution to a control without cyclodextrine. The effect of prophylaxis was clearly associated with a higher bioavailable dose of itraconazole. Antifungal prophylaxis with itraconazole effectively prevents proven invasive fungal infections and-shown for the first time for antifungal prophylaxis-reduces mortality from these infections and the rate of invasive Aspergillus infections in neutropenic patients with hematologic malignancies. Adequate doses of the oral cyclodextrine solution (at least 400 mg/d) or i.v. formulations (200 mg/d) of itraconazole are necessary for these effects.

Antifungal prophylaxis to prevent invasive mycoses among bone marrow transplantation recipients.

We reviewed the effect of systemic, intranasal, and lipid formulations of amphotericin B, fluconazole, itraconazole for antifungal prophylaxis. Specifically we reviewed the effect of antifungal prophylaxis on the development of fungal colonization, frequency of superficial and invasive mycosis, and overall mortality and that due to invasive mycoses in bone marrow transplantation recipients. A MEDLINE search was conducted to identify literature describing the risk factors, epidemiology, and chemoprophylaxis of invasive mycosis in these patients. Preliminary data published as abstracts at national infectious diseases and hematology conferences within the last 5 years were included. Antifungal prophylaxis reduces fungal colonization and superficial infection. The ability of antifungal prophylaxis to prevent systemic infection or reduce the need for empiric amphotericin B depends on specific variables. Ultimately, antifungal prophylaxis has no affect on overall mortality, and very little impact on mortality attributed to fungi.