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      Anfotericina B Liposomal, Tratamiento Pediátrico en Leishmaniasis Cutánea con Falla Terapéutica Translated title: Liposomal Amphotericin B, Pediatric Treatment of Cutaneous Leishmaniasis with Therapeutic Failure


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          Resumen La leishmaniasis cutánea en Bolivia, es menos frecuente en niños. Su presencia probablemente responde a la domesticación del vector en áreas de asentamientos humanos. La anfotericina B, está indicada para el tratamiento de la leishmaniasis en adultos, sin respuesta a los antimoniales pentavalentes o sin una cura clínica de las úlceras. Esta serie de casos, tiene por objetivo compartir experiencias del empleo de anfotericina B liposomal en pacientes pediátricos con leishmaniasis cutánea y falla terapéutica a los antimoniales. Seis pacientes con estas características ingresados al servicio de Infectología del Hospital Pediátrico Manuel Asencio Villarroel, recibieron Anfotericina B liposomal 2 a 3 mg/Kg peso día, en un periodo promedio de 18 días. Se observó remisión progresiva de las úlceras durante el tratamiento y cicatrización completa a los tres meses post tratamiento. Ninguno presentó efectos adversos y las pruebas bioquímicas renales y hepáticas, se encontraban dentro de valores normales.

          Translated abstract

          Abstract The cutaneous leishmaniasis in Bolivia is less frequent in children. Its presence probably responds to the domestication of the vector in areas of human settlements. Amphotericin B is indicated for the treatment of leishmaniasis in adults, without response to pentavalent antimonials or without a clinical cure for ulcers. The objective of this series of cases is to share experiences of the use of liposomal amphotericin B in paediatric patients with cutaneous leishmaniasis and therapeutic failure of antimonials. Six patients with these characteristics admitted to the Infectology service of the Manuel Asencio Villarroel paediatric hospital, received liposomal Amphotericin B, 2 to 3 mg / kg weight day, in a mean period of 18 days. Progressive remission of the ulcers was observed during treatment and complete healing at three months of post-treatment. None had adverse effects, and the kidney and liver biochemical tests were within normal values.

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          Most cited references21

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          Liposomal Amphotericin B (AmBisome®): A Review of the Pharmacokinetics, Pharmacodynamics, Clinical Experience and Future Directions

          Liposomal amphotericin B (AmBisome(®); LAmB) is a unique lipid formulation of amphotericin B. LAmB is a standard of care for a wide range of medically important opportunistic fungal pathogens. LAmB has a significantly improved toxicity profile compared with conventional amphotericin B deoxycholate (DAmB). Despite nearly 20 years of clinical use, the pharmacokinetics and pharmacodynamics of this agent, which differ considerably from DAmB, remain relatively poorly understood and underutilized in the clinical setting. The molecular pharmacology, preclinical and clinical pharmacokinetics, and clinical experience with LAmB for the most commonly encountered fungal pathogens are reviewed. In vitro, experimental animal models and human clinical trial data are summarized, and novel routes of administration and dosing schedules are discussed. LAmB is a formulation that results in reduced toxicity as compared with DAmB while retaining the antifungal effect of the active agent. Its long terminal half-life and retention in tissues suggest that single or intermittent dosing regimens are feasible, and these should be actively investigated in both preclinical models and in clinical trials. Significant gaps remain in knowledge of pharmacokinetics and pharmacodynamics in special populations such as neonates and children, pregnant women and obese patients.
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            Challenges and new discoveries in the treatment of leishmaniasis.

            Leishmaniasis is a parasitic disease caused by a hemoflagellate, Leishmania spp. The parasite is transmitted by the bite of an infected female phlebotomine sandfly. The disease is prevalent throughout the world and in at least 88 countries. Human leishmanial infections may manifest in any of the four most common forms. Depending on the causative species, it can manifest as cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), diffused cutaneous leishmaniasis (DCL), or visceral leishmaniasis (VL). Although there are nearly 25 compounds having antileishmanial effects, only a few are used for humans and most of these are parenteral. The oldest was urea stibamine, developed in India in 1922. The original drug had severe toxic effects, and later on its pentavalent compounds were prepared, which remained the sole treatment modality for several decades and saved millions of lives. However, reports of unresponsiveness to pentavalent sodium antimony gluconate (SAG) started in the 1970s, and in some parts of India about a quarter of kala-azar cases are reported to have developed resistance even to its higher doses. This development led to successful clinical trials of pentamidine and amphotericine B. The latter, an antifungal compound, was also found to be highly nephrotoxic, and to minimize these side effects various colloidal and lipid formulations have been prepared. These preparations are comparatively safe but are exorbitantly costly. In the past two decades, more focus has been given to finding oral drugs to minimize injection-associated complications, including blood-borne infection. Various drugs were reported effective, including antifungal ketoconazole. However, the most promising drug found is an anticancer compound, miltefosine, that belongs to the alkylphosphocholine group. The drug has undergone experimental and clinical trials and found to be 94%-97% effective. However, the drug cannot be given during pregnancy and shows severe gastrointestinal side effects. Moreover, its cost will be another limiting factor. Other drugs such as paromomycin, allopurinol, and sitamaquine have been reported with variable cure rates. Because of these limitations, a combination therapy, preferably coupled with specific parasite enzyme inhibitors, is the only hope.
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              Clinical Spectrum of Leishmaniasis


                Author and article information

                Gaceta Médica Boliviana
                Gac Med Bol
                Facultad de Medicina de la Universidad Mayor de San Simón (Cochabamba, , Bolivia )
                : 44
                : 2
                : 254-259
                [2] Cochabamba Cochabamba orgnameUniversidad Mayor de San Simón orgdiv1Facultad de Medicina orgdiv2Centro Universitario de Medicina Tropical (CUMETROP) Bolivia
                [1] Cochabamba orgnameHospital pediátrico Manuel Asencio Villarroel Bolivia
                [3] Montevideo Montevideo orgnameUniversidad de la República Uruguay
                S1012-29662021000200254 S1012-2966(21)04400200254

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                : 28 October 2021
                : 28 November 2021
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 21, Pages: 6

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                CASOS CLÍNICOS

                leishmaniasis cutaneous,amphotericin B,eficacy,treatment outcome,leishmaniasis cutánea,anfotericina B,eficacia,resultado del tratamiento


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