Comparación de la eficacia y toxicidad del estibogluconato de sodio y antimoniato de meglumina en el tratamiento de leishmaniasis cutánea en Perú / Efficacy and safety of sodium stibogluconate compared to meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru

Objetivos : Comparar la eficacia y toxicidad del antimoniato de meglumina (AM) y estibogluconato sódico (EGS) en el tratamiento de leishmaniasis cutánea (LC) en un hospital general. Material y métodos : Serie de casos comparativa de 193 pacientes con LC tratados en tres ensayos clínicos con AM (n=69) y EGS (n=124) durante 2001-2010. La administración de ambas drogas fue vía endovenosa lenta de 20 mg Sb5+/kg/día por 20 días consecutivos siguiendo las normativas de la OPS y OMS. La información clínica, toxicidad y eficacia fue obtenida de las historias clínicas almacenadas en el centro de investigación según la normativa local e internacional. Resultados : Las características demográficas fueron similares entre grupos, pero el tamaño y número de lesiones fueron mayores en el grupo AM. La eficacia del tratamiento con AM fue 76,0% versus 68,4% con EGS (p=0,340) y 55,1% versus 50,8% (p=0,570) en el análisis por protocolo y de intención de tratar, respectivamente. No se observaron efectos adversos inmediatos. Los síntomas más frecuentemente reportados fueron disgeusia (37,0%), mareos (32,0%), cefalea (36,0%), artralgias (31,0%) y linfangitis (21,0%). Los tres primeros síntomas, así como elevación de transaminasas, leucopenia, trombocitopenia y QTc prolongado fueron frecuentes en el grupo EGS, pero clínica y estadísticamente no significativos. El tratamiento fue suspendido definitivamente por toxicidad severa únicamente con EGS por emesis refractaria (2 participantes) y QTc prolongado con extrasístoles (1 participante). Conclusiones : La eficacia del tratamiento con AM y EGS fue comparable. La administración endovenosa de ambos no produjo efectos adversos inmediatos, aunque sí alteraciones clínicas y laboratoriales usuales.

SUMMARY Objectives : To compare the efficacy and safety of sodium stibogluconate (SS) and meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL) in a general hospital. Methods: Case-series of 193 patients with CL treated in three clinical trials with MA (n=69) and SS (n=124) during 2001-2010. Both study drugs were administered intravenously at a slow speed at 20 mg Sb5+/kg/day for 20 consecutive days following WHO-PAHO recommendations. Clinical and safety data were gathered from clinical files. Results: Demographic characteristics were similar between the study groups, but the size and number of lesions were higher in the MA group. Efficacy was 76.0% in the MA vs. 68.4% in the SS group (p=0.340) and 55.1% vs. 50.8% (p=0.570) in the per protocol and intention to treat analysis. respectively. Side effects more frequently reported were dysgeusia (37.0%). dizziness (32.0%). headache (36.0%). arthralgia (31.0%) and lymphangitis (21.0%). These first three symptoms as well as elevation of transaminases, leukopenia, thrombocytopenia and prolonged QTc were numerically more frequent in the SS group but without reaching statistical significance. Treatment was stopped definitively for severe toxicity in the SS group due to refractory emesis (two patients) and prolonged QTc (one patient). Conclusions: The efficacy of MA and SS is comparable. The intravenous administration of these compounds did not produce immediate reactions, but it was associated with unusual clinical and laboratory abnormalities.

Leishmaniasis cutánea simuladora de pericondritis

Resumen La leishmaniasis cutánea presenta una clínica muy característica de pápula eritemato-amarillenta con costra central, en regiones expuestas, que los profesionales de la salud podemos identificar y tratar sin necesidad de biopsia. En ocasiones, se presenta con una clínica atípica que puede conducir a un error diagnóstico, con su perpetuación y malestar en el paciente. Presentamos el caso de una mujer de 53 con una placa eritema-to-exudativa por toda la extensión del pabellón auricular izquierdo de varios meses de evolución. Había sido tratada desde el inicio con antibioterapia y corticoides, sin conseguir mejoría y con un claro empeoramiento, al haberse extendido por toda la oreja. Tras la realización de la biopsia, se llegó al diagnóstico de leishmaniasis cutánea erisipeloide. Se procedió a realizar tratamiento dirigido con fluconazol y posteriores infiltraciones de antimoniato de meglumina consiguiendo su completa resolución.

Abstract Cutaneous leishmaniasis presents a very characteristic clinic of erythematous-yellowish papule with central crust, in exposed regions, that we health professionals can identify and treat without the need for a biopsy. Sometimes, it presents with an atypical clinic that can lead to a diagnostic error, with its perpetuation and discomfort in the patient. We present the case of a 53-year-old woman with an erythematous-exudative plaque throughout the extension of the left atrial pavilion of several months of evolution. It had been treated from the start with antiobiotherapy and corticosteroids, without achieving improvement and with a clear worsening, as it had spread throughout the ear. After the biopsy was performed, the diagnosis of erysipeloid cutaneous leishmaniasis was reached. Directed treatment with fluconazole and subsequent infiltrations of meglumine antimoniate were made, achieving its complete resolution.

Alterações eletrocardiográficas em pacientes com Leishmaniose Tegumentar Americana tratados com antimoniato de meglumina: revisão integrativa / Electrocardiographic changes in patients with American tegumentary leishmaniasis treated with meglumine antimoniate: integrative review

Introdução: a Leishmaniose Tegumentar Americana (LTA) é uma infecção zoonótica cujo tratamento é realizado com a droga antimoniato de meglumina (AM). Objetivo: Relatar as alterações eletrocardiográficas decorrentes do uso de AM em pacientes com LTA. Metodologia: foi realizada uma revisão integrativa da literatura por meio das bases de dados BIREME, PUBMED, COCHRANE, SCIELO e literatura cinzenta, usando como estratégia de busca o cruzamento dos seguintes descritores, nos idiomas português e inglês: leishmaniose cutânea, eletrocardiografia, meglumina e toxicidade. Não foi estipulado um intervalo temporal para que um maior número de publicações fosse obtido. Resultados: foram encontrados 134 artigos, desses apenas 09 atenderam aos critérios de inclusão. As principais alterações eletrocardiográficas encontradas durante a terapêutica foram as alterações de repolarização ventricular, com destaque para o prolongamento do intervalo QT corrigido pela frequência cardíaca. Já entre as alterações mais graves em termos de morbimortalidade, destacam-se as arritmias ventriculares complexas, principalmente a Torsade de pointes. Discussão: em todos os artigos selecionados foram encontradas alterações ao eletrocardiograma (ECG) durante o tratamento com AM, sendo recomendado em todos os pacientes, o acompanhamento eletrocardiográfico. Apenas um estudo excluiu as alterações do ECG basal, presença de comorbidades e uso de drogas cardiotóxicas sendo esses possíveis vieses para avaliação da toxicidade cardíaca diretamente provocada pelo antimonial. Conclusão: considerando as alterações na repolarização ventricular e as possíveis arritmias ventriculares em pacientes em tratamento para LTA em uso de AM, o acompanhamento eletrocardiográfico é recomendado durante a terapêutica de todos esses pacientes, sendo útil para prevenção de complicações cardiovasculares importantes.

Introduction: American Tegumentary Leishmaniasis (ATL) is a zoonotic infection whose treatment is carried out with the meglumine antimoniate drug (AM). Objective: To report the electrocardiographic changes resulting from the use of AM in patients with ATL. Methodology: an integrative literature review was carried out using the BIREME, PUBMED, COCHRANE, SCIELO and gray literature databases, using as a search strategy the crossing of the following descriptors, in Portuguese and English: cutaneous leishmaniasis, electrocardiography, meglumine and toxicity. A time interval was not stipulated in order to obtain a greater number of publications. Results: we found 134 articles, of which only 9 met the inclusion criteria. The main electrocardiographic changes found during therapy were changes in ventricular repolarization, with emphasis on the prolongation of the QT interval corrected by heart rate. Already the most serious changes in terms of morbidity and mortality, complex ventricular arrhythmias, especially Torsade de pointes, stand out. Discussion: changes in the electrocardiogram (ECG) were found in all selected articles during treatment with AM, with electrocardiographic monitoring being recommended in all patients. Only one study excluded: changes in the baseline ECG, the presence of comorbidities and / or use of cardiotoxic drugs, these being possible biases to assess cardiac toxicity directly caused by the antimonial. Conclusion: considering the changes in ventricular repolarization and possible ventricular arrhythmias in patients undergoing treatment for ATL using AM, electrocardiographic monitoring is recommended during the therapy of all these patients, being useful for the prevention of important cardiovascular complications.

Estimating direct costs of the treatment for mucosal leishmaniasis in Brazil

Abstract INTRODUCTION: The objective of this study was to estimate the direct medical costs of the treatment for mucosal leishmaniasis (ML) using three therapeutic approaches in the Brazilian context. METHODS: We performed this economic assessment from the perspective of the Brazilian public healthcare system. The following therapeutic approaches were evaluated: meglumine antimoniate, liposomal amphotericin B, and miltefosine. Direct medical costs were estimated considering four treatment components: a) drug, b) combined medical products, c) procedures, and d) complementary tests. RESULTS: Treatment with meglumine antimoniate had the lowest average cost per patient (US$ 167.66), followed by miltefosine (US$ 259.92) in the outpatient treatment regimen. The average cost of treatment with liposomal amphotericin B was US$ 715.35 both in inpatient regimen. In all estimates, the drugs accounted for more than 60% of the total cost for each treatment approach. CONCLUSIONS: These results demonstrate the marked differences in costs between the therapeutic alternatives for ML. In addition to efficacy rates and costs related to adverse events, our data have the potential to support a complete cost-effectiveness study in the future. Complete analyses comparing costs and benefits for interventions will assist health managers in choosing drugs for ML treatment in Brazil as well as in establishing effective public health policies.

Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice

Cutaneous leishmaniasis (CL) is a parasitic disease caused by the protozoan Leishmania spp. Pentavalent antimonial agents have been used as an effective therapy, despite their side effects and resistant cases. Their pharmacokinetics remain largely unexplored. This study aimed to investigate the pharmacokinetic profile of meglumine antimoniate in a murine model of cutaneous leishmaniasis using a radiotracer approach. Methods: Meglumine antimoniate was neutron-irradiated inside a nuclear reactor and was administered once intraperitoneally to uninfected and L. amazonensis-infected BALB/c mice. Different organs and tissues were collected and the total antimony was measured. Results: Higher antimony levels were found in infected than uninfected footpad (0.29% IA vs. 0.14% IA, p = 0.0057) and maintained the concentration. The animals accumulated and retained antimony in the liver, which cleared slowly. The kidney and intestinal uptake data support the hypothesis that antimony has two elimination pathways, first through renal excretion, followed by biliary excretion. Both processes demonstrated a biphasic elimination profile classified as fast and slow. In the blood, antimony followed a biexponential open model. Infected mice showed a lower maximum concentration (6.2% IA/mL vs. 11.8% IA/mL, p = 0.0001), a 2.5-fold smaller area under the curve, a 2.7-fold reduction in the mean residence time, and a 2.5-fold higher clearance rate when compared to the uninfected mice. Conclusions: neutron-irradiated meglumine antimoniate concentrates in infected footpad, while the infection affects antimony pharmacokinetics.(AU)

Successful treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate: A case series

Abstract Cutaneous leishmaniasis (CL) is a high-morbidity, vector-borne disease endemic to Colombia. Unlike conventional systemic antileishmanial therapy, intralesional meglumine antimoniate administration has fewer adverse effects and can be as effective and safe. We describe 12 patients treated with intralesional meglumine antimoniate: seven with primary and five with recurrent lesions. The majority (11/12) met all cure criteria after 1-7 sessions of meglumine antimoniate administration (1-5 mL). Adverse effects comprised mainly of local pain and edema. Intralesional meglumine antimoniate administration could be an excellent alternative treatment for uncomplicated CL; however, controlled clinical trials are needed to test the efficacy and safety thereof.

Favorable responses to treatment with 5 mg Sbv/kg/day meglumine antimoniate in patients with American tegumentary leishmaniasis acquired in different Brazilian regions

Abstract INTRODUCTION: Favorable responses in American tegumentary leishmaniasis (ATL) patients to treatment with 5 mg Sbv/kg/day meglumine antimoniate (MA) has been reported in Rio de Janeiro, but little is known regarding the therapeutic response to low doses in patients from other locations. METHODS: A retrospective review of medical records was conducted to compare the therapeutic response to 5 mg Sbv/kg/day MA treatment among 36 patients who acquired ATL in Brazilian states other than Rio de Janeiro (OS group) and 72 patients from Rio de Janeiro (RJ group). RESULTS: One course of 5 mg Sbv/kg/day MA cured 72.8% of 81 cutaneous (CL) and 66.6% of 27 mucosal (ML) leishmaniasis-infected patients: 70% in the CL/RJ group, 81% in the CL/OS group, 50% in the ML/RJ group, and 80% in the ML/OS group. After up to two additional treatment courses at the same dose, 88.9% and 85.2% of the CL and ML patients were cured, respectively. Adverse events were observed in 40% of patients in the CL/RJ group, 57% of the CL/OS group, 58% of the ML/RJ group, and 80% of the ML/OS group. No significant differences were observed in the cure rates or adverse effects between the RJ and OS groups. No patients required permanent discontinuation of treatment due to adverse events. CONCLUSIONS: Patients with ATL acquired in both RJ and OS may respond to low-dose MA. While high-dose MA should remain the standard treatment for ATL, low-dose MA might be preferred when toxicity is a primary concern.

Mucosal leishmaniasis: the experience of a Brazilian referral center

Abstract INTRODUCTION Pentavalent antimonials (Sbv) are the most commonly used drugs for the treatment of mucosal leishmaniasis (ML), despite their high toxicity and only moderate efficacy. The aim of this study was to report therapeutic responses with different available options for ML. METHODS This study was based on a review of clinical records of 35 patients (24 men and 11 women) treated between 2009 and 2015. RESULTS The median age of patients was 63 years, and the median duration of the disease was 24 months. Seventeen patients received Sbv, while nine patients were treated with liposomal amphotericin B (AmB), and another nine patients were treated with fluconazole. Patients treated with AmB received a total median accumulated dose of 2550mg. The mean duration of azole use was 120 days, and the daily dose ranged from 450 to 900mg. At the three-month follow-up visit, the cure rate was 35%, 67%, and 22% for Sbv, AmB, and azole groups, respectively. At the six-month follow-up visit, the cure rates for Sbv, AmB, and azole groups were 71%, 78%, and 33%, respectively. CONCLUSIONS There is a scarcity of effective ML treatment alternatives, and based on our observations, fluconazole is not a valid treatment option.

Towards a standard protocol for antimony intralesional infiltration technique for cutaneous leishmaniasis treatment

BACKGROUND Despite its recognised toxicity, antimonial therapy continues to be the first-line drug for cutaneous leishmaniasis (CL) treatment. Intralesional administration of meglumine antimoniate (MA) represents an alternative that could reduce the systemic absorption of the drug and its side effects. OBJECTIVES This study aims to validate the standard operational procedure (SOP) for the intralesional infiltration of MA for CL therapy as the first step before the assessment of efficacy and safety related to the procedure. METHODS The SOP was created based on 21 trials retrieved from the literature, direct monitoring of the procedure and consultation with experts. This script was submitted to a formal computer-aided inspection to identify readability, clarity, omission, redundancy and unnecessary information (content validation). For criterion and construct validations, the influence of critical condition changes (compliance with the instructions and professional experience) on outcome conformity (saturation status achievement), tolerability (pain referred) and safety (bleeding) were assessed. FINDINGS The median procedure length was 12 minutes and in 72% of them, patients classified the pain as mild. The bleeding was also classified as mild in 96.6% of the procedures. Full compliance with the SOP was observed in 66% of infiltrations. Despite this, in 100% of the inspected procedures, lesion saturation was observed at the end of infiltration, which means that it tolerates some degree of modification in its execution (robustness) without prejudice to the result. CONCLUSIONS The procedure is reproducible and can be used by professionals without previous training with high success and safety rates.

Meglumine antimoniate intralesional infiltration for localised cutaneous leishmaniasis: a single arm, open label, phase II clinical trial

BACKGROUND Cutaneous leishmaniasis (CL) is a world-wide health problem which currently lacks effective, affordable and easy to use therapy. Recently, the meglumine antimoniate (MA) intralesional infiltration was included among the acceptable therapies for New World leishmaniasis. While this approach is attractive, there is currently little evidence to support its use in Americas. OBJECTIVES The aim of this study was to provide information about effectiveness and safety of a standardised MA intralesional infiltration technique for the treatment of CL. METHODS It is a single-arm phase II clinical trial conducted at a Brazilian referral centre. CL cases with parasitological confirmation presenting a maximum of three CL-compatible skin lesions were treated with weekly MA intralesional infiltration by using a validated technique, up to a maximum of eight infiltrations. RESULTS A total of 53 patients (62 lesions) were included. Overall, patients received a median of seven infiltrations (IQR25-75% 5-8) over a median treatment period of 43 days (IQR25-75% 28-52 days). The definitive cure rate at D180 was 87% (95% CI:77-96%). The majority of adverse events were local, with mild or moderate intensity. Bacterial secondary infection of the lesion site was observed in 13% of the treated patients, beside two intensity-three adverse events (hypersensitivity reactions).

Low dose systemic or intralesional meglumine antimoniate treatment for American tegumentary leishmaniasis results in low lethality, low incidence of relapse, and low late mucosal involvement in a referral centre in Rio de Janeiro, Brazil (2001-2013)

BACKGROUND American tegumentary leishmaniasis (ATL) is a non-lethal parasitic disease that presents with cutaneous (CL) and mucosal (ML) clinical forms. ATL treatment aims at healing the lesions and preventing the development of the late mucosal form. Systemic meglumine antimoniate (MA) therapy with 10-20 mg Sb5+/kg/day is the first choice of treatment. However, alternative therapies using 5 mg Sb5+/kg/day or intralesional (IL) MA are the usual regimens at the National Institute of Infectious Diseases (NIID), Rio de Janeiro, Brazil. OBJECTIVES To evaluate lethality and the incidence of relapse and development of late ML in CL patients treated at NIID from 2001 until 2013. METHODS Data were recovered from records of all ATL patients diagnosed during that period. FINDINGS Out of 777 patients, 753 were treated with MA (96.9%). Of those, 89.1% received alternative therapy of 9.9% IL and 79.2% systemic 5 mg Sb5+/kg/day. Some patients required 1-3 additional courses of treatment, thus making a total of 997 courses; 85.2% of them were subjected to alternative therapies. Lethality was 0.1%, relapse incidence 5.8%, and late ML incidence 0.25%. As a final outcome for the 777 patients, 95.9% were cured, 0.1% died and 4.0% were not able to follow-up. MAIN CONCLUSIONS Alternative MA schedules resulted in low lethality without increase of relapse or late ML incidence.

Intralesional treatment with meglumine antimoniate in three patients with New World cutaneous leishmaniasis and large periarticular lesions with comorbidities

Abstract Although New World cutaneous leishmaniasis is not itself a life-threatening disease, its treatment with systemic antimonials can cause toxicity that can be dangerous to some patients. Intralesional meglumine antimoniate provides a viable, less toxic alternative. Herein, we describe an alternative treatment with subcutaneous intralesional injections of meglumine antimoniate into large periarticular lesions of three patients with cutaneous leishmaniasis and comorbidities. This treatment was safe, successful, and well tolerated. This case series suggests that intralesional meglumine antimoniate is an effective therapy for cutaneous leishmaniasis, even with periarticular lesions. This hypothesis should be tested in controlled clinical trials.

Standardization of intralesional meglumine antimoniate treatment for cutaneous leishmaniasis

Abstract INTRODUCTION: Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. METHODS Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. RESULTS The technique is described in detail sufficient to enable replication. CONCLUSIONS: The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.

Leishmanasis mucocutánea tratada con miltefosine / Mucocutaneous leishmaniasis treated with miltefosine

El miltefosine (Impávido(r)) es un medicamento de componente antineoplásico que ha encontrado efectividad muy alta contra la leishmaniasis mucocutánea y visceral en el mundo, y se ha convertido en una opción muy atractiva para pacientes con enfermedades de fondo y tratamientos de base que contraindican el uso de amoniato de meglumina (Glucantime(r)) o stibogluconato de sodio (Pentostam(r)). Seguidamente se presenta el caso de un paciente de 78 años con antecedentes de diabetes mellitustipo 2, hipertenso, anticoagulado con warfarina por una fibrilación auricular crónica, que inició una dermatosis ulcerosa de bordes violáceos elevados, única en el hélix del oído derecho, de evolución crónica asociada a múltiples ulceraciones en la mucosa nasal. La biopsia cutánea se reportó como inespecífica, pero como la sospecha clínica era alta de leishmaniasis, se realizó una reacción de cadena polimerasa de tejido de mucosa nasal que fue reportada positiva por Leishmania panamensis. Por las comorbilidades y el tratamiento del paciente se decidió tratarlo con miltefosine (Impávido(r)).

Miltefosine (Impavido(r)) is an anticancer medicine that has been found highly effective against mucocutaneous and visceral leishmaniasis worldwide, making it a very attractive option for patients with underlying diseases and treatments that contraindicate the use of glucamine antimoniate (Glucantime(r)) or sodium stibogluconate (Pentostam(r)). Here we present the case of a 78 years old male, with a history of type 2 diabetes mellitus, high blood preasure, anticoagulated with warfarin for chronic atrial fibrillation, who started with a solitary cutaneous ulcer of purplish edges on the right ear helix of chronic evolution associated with multiple ulcerations on the nasal mucosa. Skin biopsy was reported as nonspecific, but as clinical suspicion of leishmaniasis was high, a polymerase chain reaction of nasal mucosa tissue was performed for Leishmania with positive results for Leishmania panamensis. Due to comorbidities and the treatment of our patient we decided to use miltefosine (Impavido(r)) for 2 months with very good results.

Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity

Abstract: INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative and more effective therapeutic strategy is to use liposomes as carriers of the antileishmanial agents. The aims of this study were to develop antimonial drugs entrapped into phosphatidylserine liposomes and to analyze their biological and physicochemical characteristics. METHODS: Liposomes containing meglumine antimoniate (MA) or pentavalent antimony salt (Sb) were obtained through filter extrusion (FEL) and characterized by transmission electron microscopy. Promastigotes of Leishmania infantum were incubated with the drugs and the viability was determined with a tetrazolium dye (MTT assay). The effects of these drugs against intracellular amastigotes were also evaluated by optical microscopy, and mammalian cytotoxicity was determined by an MTT assay. RESULTS: Liposomes had an average diameter of 162nm. MA-FEL showed inhibitory activity against intracellular L. infantum amastigotes, with a 50% inhibitory concentration (IC50) of 0.9μg/mL, whereas that of MA was 60μg/mL. Sb-FEL showed an IC50 value of 0.2μg/mL, whereas that of free Sb was 9μg/mL. MA-FEL and Sb-FEL had strong in vitro activity that was 63-fold and 39-fold more effective than their respective free drugs. MA-FEL tested at a ten-times higher concentration than Sb-FEL did not show cytotoxicity to mammalian cells, resulting in a higher selectivity index. CONCLUSIONS: Antimonial drug-containing liposomes are more effective against Leishmania-infected macrophages than the non-liposomal drugs.

Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil

Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions ...

First report onoototoxicity of meglumine antimoniate / Primeiro relato de ototoxicidade pelo antimoniato de meglumina

Introduction: Pentavalent antimonials are the first drug of choice in the treatment of tegumentary leishmaniasis. Data on ototoxicity related with such drugs is scarcely available in literature, leading us to develop a study on cochleovestibular functions. Case Report: A case of a tegumentary leishmaniasis patient, a 78-year-old man who presented a substantial increase in auditory threshold with tinnitus and severe rotatory dizziness during the treatment with meglumine antimoniate, is reported. These symptoms worsened in two weeks after treatment was interrupted. Conclusion: Dizziness and tinnitus had already been related to meglumine antimoniate. However, this is the first well documented case of cochlear-vestibular toxicity related to meglumine antimoniate.

Introdução: Antimoniais pentavalentes são os fármacos de primeira escolha no tratamento da leishmaniose tegumentar. Dados de ototoxicidade relacionados a tais fármacos são escassos na literatura, o que nos levou a desenvolver um estudo de funções cócleo-vestibulares. Relato de caso: Relatamos caso de paciente masculino de 78 anos com leishmaniose tegumentar, que apresentou aumento significativo dos limiares auditivos com zumbido e tontura rotatória grave durante o tratamento com antimoniato de meglumina. Os sintomas pioraram até duas semanas após a interrupção do tratamento. Conclusão: Tontura e zumbido já tinham sido associados ao antimoniato de meglumina. Entretanto, este é o primeiro caso bem documentado de toxicidade cócleo-vestibular relacionado ao antimoniato de meglumina.

Resolution of cttaneous leishmaniasis after acue eczema due to intralesional mmeglumine antimoniate / Resolução de leishmaniose cutânea após eczema agudo devido a antimoniato de meglumina intralesional

We report a case of a 42 year-old female, who came to a leishmaniasis reference center in Rio de Janeiro, Brazil, presenting a cutaneous leishmaniasis lesion in the right forearm. Treatment with low-dose intramuscular meglumine antimoniate (MA) (5 mg Sb5+/kg/day) was initiated, with improvement after 28 days, although with the development of generalized eczema. After 87 days, the lesion worsened. Patient refused treatment with amphotericin B. MA was then infiltrated in the lesion, in two sessions, resulting in local eczema, with bullae formation; however, twenty days after, both the ulcer and eczema receded. Intralesional administration of MA should be used carefully when previous cutaneous hypersensitivity is detected.

Relatamos caso de paciente de 42 anos atendida em centro de referência em leishmanioses no Rio de Janeiro, Brasil, apresentando lesão de leishmaniose cutânea no antebraço direito. Iniciado tratamento com baixa dose de antimoniato de meglumina (AM) intramuscular (5 mg Sb5+/kg/dia), houve melhora após 28 dias, porém com desenvolvimento de eczema generalizado. Após 87 dias, notou-se piora da lesão. A paciente recusou o tratamento com anfotericina B. Infiltrou-se AM na lesão em duas sessões, resultando em eczema local com bolhas. Entretanto, 20 dias depois, tanto a úlcera quanto o eczema regrediram. A administração intralesional do AM deve ser utilizada com cautela em pacientes com hipersensibilidade cutânea a este fármaco.

Tratamento intralesional da leishmaniose cutânea com antimoniato de meglumina no instituto de pesquisa clínica Evandro Chagas, Fiocruz, Rio de Janeiro (2002 a julho 2011) / Intralesional treatment of cutaneous leishmaniasis with meglumine antimoniate at the institute of clinical research Evandro Chagas, Fiocruz, Rio de Janeiro (2002 to July 2011)

A leishmaniose tegumentar americana é uma doença que acomete a pele e as mucosas das vias aero digestivas superiores. Os antimoniais pentavalentes vêm sendo empregados há muitas décadas como fármacos de primeira linha para o seu tratamento. Pacientes com poucas lesões cutâneas, com impossibilidade de receber medicação parenteral regular ou com sinais de toxicidade importante ao antimonial por via sistêmica, podem ser submetidosao tratamento intralesional com antimoniato de meglumina. Objetivos:descrever a eficácia e a segurança do antimoniato de meglumina administrado por via intralesional, para o tratamento da leishmaniose cutânea. Método: Foi realizado um estudo descritivo, retrospectivo, tipo série de casos, de pacientes atendidos no Laboratório de Vigilância em Leishmanioses do Instituto de Pesquisa Clínica Evandro Chagas – FIOCRUZ, de 2002 até julho de 2011, que tivessem sido tratados para leishmaniose cutânea com aplicação intralesional de antimoniato de meglumina, após tratamento sistêmico com o mesmo fármaco...

American tegumentary leishmaniasis is a disease that affects the skin and mucous membranes of the upper aerodigestive tract. Pentavalent antimonial compounds have been used for decades as a first-line drugs for its treatment.Patients with few skin lesions, with inability to receive parenteral medication regularly or with signs of significant toxicity to antimony systemically, may be subjected to treatment with intralesional meglumine antimoniate. Objectives: Todescribe the efficacy and safety of meglumine antimoniate administered intralesionally, for the treatment of cutaneous leishmaniasis. Methods: We conducted a descriptive, retrospective case series of patients treated at the Leishmaniasis Surveillance Laboratory, Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, from 2002 until July2011, which had been treated for cutaneous leishmaniasis with intralesional meglumine antimoniate after systemic treatment with the same drug...

Distribución de los niveles séricos de amilasa en pacientes con leishmaniasis cutánea en tratamiento con antimoniato de meglumina / Distribution of serum amylase levels in patients with cutaneous leishmaniasis treated with meglumina antimoniate

El tratamiento de elección para la leishmaniasis es el antimoniato de meglumina, del cual se han reportado efectos pancreáticos. Se llevó a cabo un estudio con 90 pacientes entre agosto de 2010 y abril de 2011, y se observó la variabilidad de la amilasa al inicio, la mitad y el final del tratamiento con dosis de 20 mg/kg al día. Los promedios fueron: peso, 68±9,1 kg, edad, 24,73±4,45 años, y dosis del medicamento, 28,15±3,97g. El sitio de lesión más frecuente fue en miembros superiores (44,4%). No hubo asociación significativa entre las variables peso, edad y gramos de medicamento. Se presentó alteración en 49,37% a la mitad de tratamiento y en 6,5% al final. Existen diferencias significativas en la amilasa reportada a mitad de tratamiento respecto alas dos tomas (p=0,000). En conclusión, se debe controlar la amilasa sérica, ya que se eleva, especialmente, a mitad de tratamiento...

The treatment of choice for leishmaniasis is meglumine antimoniate, reporting effects at the pancreatic duct. A study with 90 patients between August 2010 and April 2011 found amylase changes at the beginning, middle and end of treatment at doses of 20 mg/kg/day. The averages were: weight, 68 kg±9.1, age 24.73±4.45 years, and 28.15±3.97 g of the drug dose. The site of injury was 44,4% in upperlimbs. No significant association was found between the variables weight, age and treatment programs. Alteration was present in 49,37% inthe middle of treatment and 6,5% at the end. There were significant differences in reported half-amylase treatment on the two doses (p=0.000). In conclusion, control must be performed in serum amylase and rising especially in the middle of treatment...