scholarly journals Lipid Amphotericin B Formulations as Comparators in Clinical Trials

2004 ◽  
Vol 38 (2) ◽  
pp. 305-306 ◽  
Author(s):  
John H. Powers ◽  
Renata Albrecht
Keyword(s):  
Clinical Trials ◽  
Amphotericin B ◽  
Lipid Amphotericin B

scholarly journals Fixed Dosing of Liposomal Amphotericin B in Morbidly Obese Individuals

2019 ◽  
Vol 70 (10) ◽  
pp. 2213-2215 ◽  
Author(s):  
Roeland E Wasmann ◽  
Cornelis Smit ◽  
Eric P H van Dongen ◽  
René M J Wiezer ◽  
Jill Adler-Moore ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Body Size ◽  
Prospective Study ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Liposomal Amphotericin B ◽  
Fixed Dose ◽  
Morbidly Obese

Abstract In this prospective study, we examined the pharmacokinetics of 1 and 2 mg/kg liposomal amphotericin B in 16 morbidly obese individuals (104–177 kg). Body size had no effect on clearance. We recommend a fixed dose in patients ≥100 kg (ie, 300 or 500 mg rather than the current dose of 3 and 5 mg/kg, respectively). Clinical Trials Registration NCT02320604.

Fluconazole and Amphotericin B for Cryptococcal Meningitis

1996 ◽  
Vol 30 (12) ◽  
pp. 1408-1410 ◽  
Author(s):  
Amy B Clark ◽  
Bob L Lobo ◽  
Michael S Gelfand
Keyword(s):  
Clinical Trials ◽  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Patient Population ◽  
Standard Therapy ◽  
Alternative Therapy ◽  
Poor Response ◽  
Case Summary

OBJECTIVE: To describe a patient with cryptococcal meningitis treated with the combination of amphotericin B and fluconazole. CASE SUMMARY: A 41-year-old woman with cryptococcal meningitis who was not infected with HIV was treated with a combination of amphotericin B and fluconazole because she did not respond to amphotericin B alone and could not tolerate amphotericin B with flucytosine. She improved clinically, but it is unclear whether the combination was beneficial. DISCUSSION: Standard therapy for cryptococcal meningitis is amphotericin B with or without flucytosine. Fluconazole is an alternative therapy, but its efficacy has not been documented in the patient population not infected with HIV. Theoretically, the combination of amphotericin B and fluconazole is antagonistic, but in vitro and in vivo data suggest that antagonism may not occur. The combination of amphotericin B and fluconazole in cryptococcal meningitis has not been evaluated in clinical trials, and its use is not recommended. CONCLUSIONS: A patient with cryptococcal meningitis was treated with the combination of amphotericin B and fluconazole because of a poor response to amphotericin B monotherapy and intolerance to flucytosine. It is unclear whether her clinical response was a result of the combination.

Analysis of Efficacy, Safety and Costs of Systemic Antifungal Agents in 159 Consecutive High-Risk Cancer Patients for the Establishment of Standardized Guidelines

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1313-1313
Author(s):  
Werner Neubauer ◽  
Martina Kleber ◽  
Alf Zerweck ◽  
Veronique Thierry ◽  
Alexandra Goebel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Amphotericin B ◽  
Median Duration ◽  
Liposomal Amphotericin ◽  
Immunosuppressive Agents ◽  
Antifungal Drugs ◽  
Liposomal Amphotericin B ◽  
High Morbidity ◽  
Cell Transplant ◽  
Line Therapy

Abstract Introduction: Invasive mycoses (IM) show high morbidity and mortality rates in immunocompromised patients (pts), especially among allogeneic stem cell transplant (allo-SCT) recipients. Efficacy and safety profiles of currently available systemic antifungal drugs (SAD) have been derived from various clinical trials, which, however, do not reflect ‘everyday clinics’ and true SAD efficacy in cancer pts due to tight inclusion and exclusion study criteria. The aim of our analysis is the development of standard operating procedures (SOP) for SAD use also outside clinical trials, leading to less application errors (thereby enhancing treatment safety) and an economically appropriate SAD use. Methods: Since 11/06, we prospectively analyse the use of SAD on a general hematology ward (n=43) and SCT-unit (n=116) within our department. We assess pt characteristics, organ functions, side effects (SE), potential drug interactions (PDI), treatment outcomes and costs. Data is obtained by daily participation on ward rounds, consultation of ward physicians and review of pts’ medication charts. SAD were given according to EORTC-adapted guidelines, with use of fluconazole as primary prophylaxis in allo-SCT recipients and voriconazole or posaconazole as secondary prophylaxis after aspergillus or zygomycetes infection. Empirical therapy was implemented with liposomal amphotericin, preemptive therapy and therapy of aspergillus infections with voriconazole, caspofungin or liposomal amphotericin B. Results: So far, data from 159 consecutive pts have been obtained, showing a median age of 57 years (y; range 20–85) and a median Satariano index of 1 (comorbidity index; range 0–4). The underlying malignancies comprised leukemia (n=98), lymphoma (n=41), solid tumors (n=12) and other non-malignant diseases (n=8) with the majority of pts having undergone allo- (n=110) or autologous (n=31) SCT. Subgroup analyses showed that transplant pts were treated more frequently with intravenous (iv) SAD and with two or more consecutively applied SAD, compared with pts on the general hematology ward (Table 1). Transplant pts received SAD earlier with higher pt numbers being treated prophylactically and empirically. Due to often complex co-medication (e.g. antibiotics, immunosuppressive agents), PDI were detected more often among transplant pts. The median duration of SAD use was considerably longer and the median SAD costs exceeded those of the pts treated on the general hematological ward. Table 1. Use of systemic antifungal drugs (SAD) on a general hematology ward vs. SCT-unit All patients General hematology ward SCT-unit # pts 159 43 116 Median age (y) 57 62 54 Pts treated with iv SAD (%) 86 (54%) 11 (26%) 75 (65%) Pts treated consecutively with >2 SAD (%) 25 (16%) 1 (2%) 24 (21%) Pts treated prophylactically (%) 119 (75%) 22 (51%) 97 (84%) Pts treated empirically (%) 55 (35%) 12 (28%) 43 (37%) Pts with >1 PDI per SAD (%) 62 (39%) 6 (14%) 56 (48%) Median duration of SAD treatment (d) 30 10 32.5 Median SAD costs per hospital stay (US $) 1325 130 2997 Notable was also the comparison of pts receiving caspofungin vs. liposomal amphotericin B, whereby the echinocandin showed a more favorable safety profile, less SE and PDI (Table 2). Caspofungin was more frequently applied as preemptive and 2-line therapy, whereas liposomal amphotericin B was commonly used as empirical and 1-line therapy. Table 2. Therapeutical use of caspofungin vs. liposomal amphotericin B All patients Caspofungin lip. Ampho B # pts 82 21 61 Median age (y) 57 56 57 Pts with >1 SE (%) 12 (15%) 2 (10%) 11 (18%) Pts with >2 PDI (%) 30 (37%) 0 30 (49%) Pts treated empirically (%) 55 (67%) 9 (43%) 46 (75%) Pts treated preemptively (%) 21 (26%) 10 (48%) 11 (18%) Median therapy line 1 2 1 Posaconazole surprisingly showed an unfavorable toxicity profile in our hands and (mainly hepatic) SE in 5/5 pts. Conclusions: Earlier onset and longer SAD treatment duration lead to substantial costs on our SCT-unit compared to a general hematology ward. PDI emerge much more frequent due to complex co-medication. Caspofungin appears to be more favorably tolerated than liposomal amphotericin B concerning SE as well as PDI. Due to our detection of frequent SE and PDI with SAD, SOPs for their use should help to avoid errors and will impact on pts’ safety. Enrollment of additional pts, especially with induction/consolidation treatment for acute leukemia, is ongoing, which will be presented at the meeting.

Efficacious topical treatment for human cutaneous leishmaniasis with ethanolic lipid amphotericin B

2001 ◽  
Vol 95 (2) ◽  
pp. 184-186 ◽  
Author(s):  
Daniel Vardy ◽  
Yechezkel Barenholz ◽  
Natalia Naftoliev ◽  
Sidney Klaus ◽  
Leon Gilead ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Amphotericin B ◽  
Topical Treatment ◽  
Lipid Amphotericin B ◽  
Human Cutaneous Leishmaniasis

scholarly journals Serious adverse events following treatment of visceral leishmaniasis: A systematic review and meta-analysis

2021 ◽  
Vol 15 (3) ◽  
pp. e0009302
Author(s):  
Sauman Singh-Phulgenda ◽  
Prabin Dahal ◽  
Roland Ngu ◽  
Brittany J. Maguire ◽  
Alice Hawryszkiewycz ◽  
...  
Keyword(s):  
Systematic Review ◽  
At Risk ◽  
Clinical Trials ◽  
Visceral Leishmaniasis ◽  
Adverse Events ◽  
Amphotericin B ◽  
Treatment Initiation ◽  
Meta Analysis ◽  
Eastern Africa ◽  
Serious Adverse Events

Background Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs). Methods For this updated systematic review, we searched the following databases from 1st Jan 2016 through 2nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from individual treatment arms were combined in a meta-analysis using random effects Poisson regression. Results We identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal amphotericin B (L-AmB) in 52 (15.0%), amphotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), amphotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041–0.114; I2 = 81.4%; 95% prediction interval (PI): 0.001–2.779] per 1,000 person-days at risk; the rate was 0.628 [95% CI: 0.368–1.021; I2 = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021–0.081; I2 = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244–1.355; I2 = 91.9%] compared to 0.043 [95% CI: 0.020–0.090; I2 = 62.5%] in 160 arms which excluded HIV co-infections. Conclusion Mortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble individual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.

scholarly journals Therapy of Mucormycosis

2018 ◽  
Vol 4 (3) ◽  
pp. 90 ◽  
Author(s):  
Nikolaos V. Sipsas ◽  
Maria N. Gamaletsou ◽  
Amalia Anastasopoulou ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Clinical Trials ◽  
Amphotericin B ◽  
Opportunistic Infection ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Management Plan ◽  
Current Status ◽  
Pharmacological Properties ◽  
Different Types ◽  
Individualized Management

Despite the recent introduction of mold-active agents (posaconazole and isavuconazole), in addition to amphotericin B products, to our armamentarium against mucormycosis, many uncertainties remain for the management of this uncommon opportunistic infection, as there are no data from prospective randomized clinical trials to guide therapy. In this mini-review, we present the current status of treatment options. In view of the heterogeneity of the disease (different types of affected hosts, sites of infection, and infecting Mucorales), mucormycosis management requires an individualized management plan that takes into account the net state of immunosuppression of the host, including comorbidities, certainty of diagnosis, site of infection, and antifungal pharmacological properties.

Hematogenous Candidiasis in Critically Ill Adult Patients: Epidemiology, Risk Factors and Management

1998 ◽  
Vol 11 (6) ◽  
pp. 437-451
Author(s):  
John Papadopoulos
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Amphotericin B ◽  
Critically Ill ◽  
Clinical Setting ◽  
Critically Ill Patients ◽  
Candida Species ◽  
Blood Cultures ◽  
The Past ◽  
Life Threatening

Hematogenous candidiasis is a life-threatening infection that occurs in critically ill patients. The incidence has increased dramatically over the past decade and Candida species are currently the fourth most common organism recovered from blood cultures in hospitalized patients. Numerous risk factors have been identified that predispose a patient to the development of hematogenous candidiasis. Diagnosis is often difficult in the clinical setting. Pharmacologic options for the management of hematogenous candidiasis includes amphotericin B, fluconazole, and flucytosine. Evidence from clinical trials indicate that fluconazole is as effective and better tolerated than amphotericin B for the management of hematogenous candidiasis in critically ill patients.

Pharmacotherapy of Disseminated Histoplasmosis in Patients with AIDS

1993 ◽  
Vol 27 (12) ◽  
pp. 1510-1518 ◽  
Author(s):  
S. Diane Goodwin ◽  
Courtney V. Fletcher ◽  
Richard H. Drew
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Maintenance Therapy ◽  
Amphotericin B ◽  
Induction Therapy ◽  
Antifungal Agent ◽  
Clinical Presentation ◽  
Biomedical Literature ◽  
Aids Patients ◽  
Disseminated Histoplasmosis

OBJECTIVE: To review the pharmacotherapy of disseminated histoplasmosis (DH) in patients with AIDS. The article provides an overview of the pathophysiology, epidemiology, clinical presentation and diagnosis of this disease. Clinical trials reporting intervention with antifungal therapy are reviewed, with an emphasis on efficacy and toxicity of these agents. DATA SOURCES: A MEDLINE search from 1976 to the present was performed to identify pertinent biomedical literature, including reviews. STUDY SELECTION: All available reviews and clinical trials in AIDS patients were evaluated, as were all available case series and interventional clinical trials. DATA SYNTHESIS: DH in patients with HIV infection is an AIDS-defining opportunistic infection caused by Histoplasma capsulatum. It is most frequently observed in HIV-infected patients living in or traveling to endemic regions. The clinical presentation most often includes fever and weight loss, but may be complicated by comorbid illness such as other opportunistic infections. Diagnosis is best established by histologic examination of peripheral blood smear or bone marrow aspirate, or isolation of the organism in cultures of blood, bone marrow, and respiratory secretions. Serologic examinations may provide supportive diagnostic information. Detection of histoplasma polysaccharide antigen (HPA) in serum or urine may prove to be a promising approach for the rapid diagnosis and therapeutic monitoring of DH in AIDS patients. In contrast to immunocompetent hosts, high relapse rates are reported after therapy in AIDS patients. Therefore, initial (induction) therapy is routinely followed by long-term (maintenance) therapy to prevent relapse. Issues regarding the selection, dosage, and duration of therapy, as well as prophylaxis of patients at highest risk, still need to be addressed by controlled clinical trials. CONCLUSIONS: Amphotericin B is presently the drug of choice for induction therapy. Maintenance therapy with either amphotericin B or an oral azole antifungal agent active against H. capsulatum is necessary to prevent relapse. Itraconazole, a triazole antifungal agent, may provide effective alternative therapy for both induction and maintenance treatment of DH.

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