scholarly journals Reduction in the Nephrotoxicity of Amphotericin B when Administered in 20% Intralipid

1997 ◽  
Vol 8 (3) ◽  
pp. 157-160 ◽  
Author(s):  
Suzette Salama ◽  
Coleman Rotstein
Keyword(s):  
Creatinine Clearance ◽  
Total Dose ◽  
Amphotericin B ◽  
Crossover Trial ◽  
Fungal Infections ◽  
Immunocompromised Patients ◽  
Duration Of Therapy

The administration of amphotericin B (AmB) is often limited by the development of nephrotoxicity. In a pilot crossover trial, aqueous AmB followed by a new preparation of a mixture of AmB with 20% intralipid (AmB-IL) was administered to 10 immunocompromised patients for systemic fungal infections caused byCandidaspecies. Mean total dose and duration of therapy with AmB-IL exceeded that of aqueous AmB (649±165 mg versus 394±105 mg, P=0.061 and 13.2±2.5 days versus 9±2.1 days, P=0.31). However, mean creatinine clearance of the patients rose during AmB-IL therapy by 10.7±7.7 mL/min (P=0.03). AmB-IL warrants further investigation to assess its stability and efficacy for treating serious fungal infections.

scholarly journals Comparative Drug Disposition, Urinary Pharmacokinetics, and Renal Effects of Multilamellar Liposomal Nystatin and Amphotericin B Deoxycholate in Rabbits

2003 ◽  
Vol 47 (12) ◽  
pp. 3917-3925 ◽  
Author(s):  
Andreas H. Groll ◽  
Diana Mickiene ◽  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Raul M. Alfaro ◽  
...  
Keyword(s):  
Total Dose ◽  
Amphotericin B ◽  
Drug Disposition ◽  
Fungal Infections ◽  
Standard Dose ◽  
Concentration Data ◽  
Drug Concentrations ◽  
Amphotericin B Deoxycholate ◽  
Dose Dependent Decrease ◽  
Dose Dependent

ABSTRACT The comparative drug dispositions, urinary pharmacokinetics, and effects on renal function of multilamellar liposomal nystatin (LNYS; Nyotran) and amphotericin B deoxycholate (DAMB; Fungizone) were studied in rabbits. Drug concentrations were determined by high-performance liquid chromatography as total concentrations of LNYS and DAMB. In comparison to a standard dose of 1 mg of DAMB/kg of body weight, therapeutic dosages of LNYS, i.e., 2, 4, and 6 mg/kg, resulted in escalating maximum concentrations (C max) (17 to 56μ g/ml for LNYS versus 3.36 μg/ml for DAMB; P< 0.001) and values for the area under the concentration-time curve from 0 to 24 h (AUC0-24) (17 to 77μ g · h/ml for LNYS versus 12μ g · h/ml for DAMB; P < 0.001) in plasma but a significantly faster total clearance from plasma (0.117 to 0.080 liter/h/kg for LNYS versus 0.055 liter/h/kg for DAMB; P = 0.013) and a ≤8-fold-smaller volume of distribution at steady state (P = 0.002). Urinary drug concentration data revealed a ≥10-fold-higher C max (16 to 10 μg/ml for LNYS versus 0.96μ g/ml for DAMB; P = 0.015) and a 4- to 7-fold-greater AUC0-24 (63 to 35μ g · h/ml for LNYS versus 8.9μ g · h/ml for DAMB; P = 0.015) following the administration of LNYS, with a dose-dependent decrease in the dose-normalized AUC0-24 in urine (P= 0.001) and a trend toward a dose-dependent decrease in renal clearance. Except for the kidneys, the mean concentrations of LNYS in liver, spleen, and lung 24 h after dosing were severalfold lower than those after administration of DAMB (P,<0.002 to <0.001). Less than 1% each of the total dose of LNYS was recovered from the kidneys, liver, spleen, and lungs; in contrast, a quarter of the total dose was recovered from the livers of DAMB-treated animals. LNYS had dose-dependent effects on glomerular filtration and distal, but not proximal, renal tubular function which did not exceed those of DAMB at the highest investigated dosage of 6 mg/kg. The results of this experimental study demonstrate fundamental differences in the dispositions of LNYS and DAMB. Based on its enhanced urinary exposure, LNYS may offer a therapeutic advantage in systemic fungal infections involving the upper and lower urinary tracts that require therapy with antifungal polyenes.

scholarly journals A treated case of rhinocerebral zygomycosis with aspergillosis: a case report from India

2020 ◽  
Vol 2 (8) ◽  
Author(s):  
Shalini Malhothra ◽  
Sabyasachi Mandal ◽  
Rajkumari Meena ◽  
Priti Patel ◽  
Nirmaljit Kaur Bhatia ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Infections ◽  
Clinical Sample ◽  
Rapid Diagnosis ◽  
Arterial System ◽  
Immunocompromised Patients ◽  
Direct Examination ◽  
Intravenous Amphotericin ◽  
Endoscopic Debridement ◽  
Prompt Diagnosis

Zygomycosis and aspergillosis are two serious fungal infections that are commonly seen in immunocompromised patients. Since both of these infections involve fungi that invade vessels of the arterial system, an early and rapid diagnosis by direct examination of KOH mounts of the relevant clinical sample can clinch the diagnosis. Here, we present a case of a 60-year-old diabetic patient who presented with swelling and pain over the nose and left eye for 7 days with loss of vision in the left eye. After investigation, the patient was diagnosed as having rhinocerebral mucormycosis and aspergillosis, and was initially treated with amphotericin B (1 mg kg−1 day−1 intravenously), followed by endoscopic debridement under general anaesthesia. The patient gradually improved after surgery, and treatment with intravenous amphotericin B was continued along with the addition of 200 mg oral voriconazole twice daily (for the aspergillosis). With prompt diagnosis and treatment, the patient survived these fatal fungal co-infections and finally was discharged.

Amphotericin B Lipid Complex in the Management of Invasive Fungal Infections in Immunocompromised Patients

2011 ◽  
Vol 31 (11) ◽  
pp. 745-758 ◽  
Author(s):  
Matteo Bassetti ◽  
Franco Aversa ◽  
Filippo Ballerini ◽  
Fabio Benedetti ◽  
Alessandro Busca ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Immunocompromised Patients ◽  
Lipid Complex ◽  
Amphotericin B Lipid Complex

No Signs of New Toxicity When Amphotericin B Lipid Complex (ABLC, ABELCET) and Caspofungin Are Used in Combination in the Treatment of FUO.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5077-5077
Author(s):  
Rodrigo Martino ◽  
Bertrand DuPont ◽  
Helen Huckle ◽  
Raj Chopra
Keyword(s):  
Renal Failure ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Single Agent ◽  
Study Drug ◽  
Immunocompromised Patients ◽  
Multi Centre Study ◽  
Therapy Regimen ◽  
Grade 3 ◽  
Experienced Grade

Abstract BACKGROUND: Systemic fungal infections including invasive candidiasis and aspergillosis are a significant cause of mortality and morbidity in immunocompromised patients. ABLC is used for the treatment of fungal infections in patients who are intolerant or unresponsive to conventional amphotericin therapy. Caspofungin is a second-line treatment for invasive aspergillosis. The different mechanisms of action of these agents support a dual-therapy regimen; synergistic results have been observed in vitro (Arikan et al, Antimicrob Agents Chemother, 2002;46:245–47). The aim of this open-label, multi-centre study was to investigate safety, tolerability (primary endpoints) and efficacy of concomitant ABLC and caspofungin in immunocompromised patients with refractory FUO (fever of unknown origin). METHODS: At baseline patients were required to have serum creatinine≤220 μm/L, neutrophil count &lt;0.5x109/L, and at least 72 hours of fever refractory to antibiotics or a recurrence of fever despite continuing antibiotics. Patients received an initial 70 mg caspofungin IV over one hour, followed by ABLC 5 mg/kg IV over 4 hours, then caspofungin 50 mg/day and ABLC 5mg/kg/day. Medication continued until apyrexia or the patient was withdrawn from the study. Tolerability was assessed through incidence and severity of adverse events (AE) including study withdrawal due to Aes. There was a 30-day follow-up period. RESULTS: 27 immunocompromised patients (mean age 48.9, 18 male) entered the study (leukemia without transplant in 68.2% of patients, haematological malignancy with transplant in 27.3% of patients). Extent of exposure was 11.9 days (mean) for ABLC and 12.2 days (mean) for caspofungin. Safety: 27 patients were assessed for safety. 18.6% of Aes were considered related to study drug. Drug related Aes included hypokalaemia (4.9%), nausea (4.4%), rigours (4.0%), renal failure (3.5%), diarrhoea (3.5%), hypomagnesaemia (3.1%) and oliguria (1.3%). Three patients experienced grade 3 hypokalaemia related to study medication. Two patients experienced study drug related grade 3 renal failure. This is a similar incidence to single agent use of lipid-associated amphotericin B. The two patients who received concomitant ciclosporin did not develop renal toxicity. Tolerability: 22 patients were assessed (5 were excluded; 1 protocol violator (inclusion criteria), 2 had fewer than 7 doses of drug and 2 died, reasons unrelated to study drug). 20 (90.9%) patients completed the study without grade 4 or unresolved grade 3 AE. No patient experienced grade 4 AE related to the study drug. No patient withdrew from the study due to AE’s. Efficacy: 20 patients were assessed (2 patients withdrew consent before study completion). All patients achieved a normal median daily temperature after a mean of 4.3 days (range 2–16 days). CONCLUSIONS: There was no evidence of newly emerging toxicity associated with the combination of ABLC and caspofungin and no evidence of increase in known toxicity. In addition there is evidence that the combination was efficacious, but there is a clear need for additional studies to confirm this finding.

scholarly journals Safety of voriconazole in treatment of fungal infections

2020 ◽  
Vol 6 (2) ◽  
pp. 292
Author(s):  
Shobhit Mohan ◽  
Lalit Mohan ◽  
Renu Sangal Sangal ◽  
Neelu Singh
Keyword(s):  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Scedosporium Apiospermum ◽  
Immunocompromised Patients ◽  
Drug Of Choice ◽  
High Incidence ◽  
Systemic Infections ◽  
Species Being

<p class="abstract">Immunocompromised patients are at more risk in developing fungal infections particularly with <em>Candida </em>and <em>Aspergillus</em> species being the mycoses most commonly identified. Previously, amphotericin-B is the drug of choice for the treatment of systemic infections caused by <em>Candida</em> and <em>Aspergillus</em> species. Due to its high incidence of toxicity, its use has been limited in many cases. Voriconazole is the newest triazole synthesized against fungal infections and was approved by FDA in 2002 for the treatment of invasive aspergillosis and refractory infections of <em>Scedosporium apiospermum</em> and <em>Fusarium</em> spp.</p>

Antifúngicos poliénicos. Mecanismo de acción y aplicaciones

2020 ◽  
Vol 63 (2) ◽  
pp. 7-17
Author(s):  
Evelyn Rivera-Toledo ◽  
Alan Uriel Jiménez-Delgadillo ◽  
Patricia Manzano-Gayosso
Keyword(s):  
Antifungal Activity ◽  
Key Words ◽  
Secondary Metabolism ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Variable Number ◽  
Therapeutic Failure ◽  
Morbidity And Mortality ◽  
Clinical Use

The first compounds with specific antifungal activity were identified in the middle of the last century as a product of the secondary metabolism of bacteria of the order Actinomycetales, and their clinical use significantly diminished the morbidity and mortality associated with severe fungal infections. Many of such biosynthetic compounds are characterized by a chemical polygenic structure, with a variable number of carbon-carbon double bonds. Currently, besides polygenic antimycotics, there are other antifungal agents, such as the azole compounds, that have less toxicity in patients; however, cases of therapeutic failure with such compounds have been documented, therefore, the use of polygenics is still the best alternative in such cases. This review presents data about the properties and applications of antifungal-polygenic compounds using amphotericin B as a model. Key words: Amphotericin B; antifungal polyenes; ergosterol

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