Combination therapy with liposomal amphotericin b (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate in a refractory visceral leishmaniasis case

Abstract Visceral leishmaniasis is a systemic disease that is potentially severe and endemic in Brazil. It clinically manifests as fever, weight loss, swelling, hepatosplenomegaly, paleness, and edema. In this study, we discuss a case of a 1-year-old child diagnosed with refractory visceral leishmaniasis after being treated with liposomal amphotericin B in two distinct occasions. Considering the persistent clinical features and weak response to conventional treatment, a combination therapy with liposomal amphotericin B (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate was initiated, and response to treatment was good.

Treatment of American tegumentary leishmaniasis in special populations: a summary of evidence

We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericin B) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.

Influência do estado nutricional na evolução clínica e terapêutica de adultos e idosos com leishmaniose tegumentar americana / Influence of the nutritional status in the clinical and therapeutical evolution in adults and elderly with american tegumentary leishmaniasis

O objetivo deste estudo foi descrever o estado nutricional de pacientes adultos e idosos com leishmaniose tegumentar americana (LTA). Foi realizado um estudo longitudinal em 68 pacientes adultos e idosos com LTA atendidos no Laboratório de Vigilância em Leishmanioses – Instituto de Pesquisa Clínica Evandro Chagas – Fiocruz, no período de 2009 a 2012. A avaliação nutricional foi realizada através do peso, altura, Índice de Massa Corporal e albumina sérica. A evolução clínica(epitelização e cicatrização das lesões) foi avaliada até dois anos após o tratamento de LTA. A maioria da amostra era composta por homens (71%), adultos (73%), com renda familiar de 1 a 5salários mínimos (79%) e com grau de instrução fundamental incompleto (48,5%). A forma predominante da LTA foi a cutânea (72%) e 39% apresentaram comorbidades, sendo a hipertensão arterial a mais frequente (30,8%). As intercorrências clínicas e nutricionais mais prevalentes foram:redução recente na ingestão de alimentos (23,9%), obstrução nasal (22,1%), úlcera oral (14,7%),anorexia + disfagia (13,2% cada) e odinofagia (10,3%). O tempo de cicatrização foi de 145,50 ±87,84 dias para lesões cutâneas e 172,89 ± 123 dias para lesões mucosas. Foram observados baixo peso em 10% e hipoalbuminemia em 12% dos pacientes...

The objective of this study is to describe the nutritional status of adult and elderly patients with American Tegumentary Leishmaniasis (ATL). It was conducted a longitudinal study in 68 adult andelderly patients with ATL treating at the Laboratório de Vigilância em Leishmanioses (Surveillance Leishmaniasis Laboratory) at the Instituto de Pesquisa Clínica Evandro Chagas (Evandro Chagas Clinical Research Institute)-Fiocruz, from 2009 to 2012. The nutritional assessment was performedusing weight, height, the Body Mass Index (BMI) and blood albumin levels. The clinical evolution(epithelialization, and wound healing) was measured up to two years after ATL treatment. Most ofthe sample was composed of men (71%), adults (73%), with household income of 1-5 minimumwages (79%), and incomplete basic education (48.5%). The predominant ATL form was cutaneous(72%), and 39% presented comorbidities, the most frequent was hypertension (30.8%). The most prevalent clinical and nutritional events were: recent reduction in food intake (23.9%); nasal obstruction (22.1%); oral ulcer (14.7%), anorexia + dysphagia (13.2% each) and odynophagia(10.3%). The healing time was 145.50 ± 87.84 days for skin lesions, and 172.89 ± 123 days formucous membrane lesions. Low weight in 10%, and hypoalbuminemia in 12% of the patients havebeen observed...

Profilaxis de neumonía por Pneumocystis jiroveci en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against Pneumocystis pneumonia in pediatric and adult patients undergoing solid organ or hematopoietic stem cells transplantation

Pneumocystis jiroveci is an important pathogen in patients undergoing SOT and HSCT. Universal prophylaxis is recommended for all adults and children with SOT and HSCT, considering that its use significantly reduces the occurrence and mortality associated with pneumonia by this agent. The drug of choice is cotrimoxazole (A1) three times a week, low-dose scheme, that has proved equally effective and better tolerated than the daily regimen and/or at high doses. Prophylaxis starts 7 to 14 days post transplant in SOT recipients and post-implant in HSCT, with an average duration of 6 months except in liver and lung transplant as in HSCT with significant degree of immunosuppression, that lasts for 1 year. Alternatives for prophylaxis are dapsone (B2), aerosolized pentamidine (B2) and atovaquone (C2).

Pneumocystis jiroveci es un patógeno importante en pacientes sometidos a TOS y TPH. Se recomienda proilaxis universal a todos los pacientes adultos y niños sometidos a TOS o TPH porque su uso reduce signiicati-vamente la ocurrencia y mortalidad asociada a neumonía por este agente. El medicamento de elección es cotrimoxa-zol (A1) tres veces por semana, en dosis bajas, esquema que ha demostrado igual eicacia y mejor tolerancia que el esquema diario y/o con dosis altas. La proilaxis se inicia 7 a 14 días post trasplante en TOS y posterior al implante en TPH, con una duración promedio de 6 meses salvo en trasplante de hígado y pulmón en que se prolonga por 1 año, al igual que en TPH con grado importante de inmunosupresión. Son alternativas de profilaxis dapsona (B2), pentamidina aerosolizada (B2) y atavacuona (C2).

A randomized clinical trial of low dosage combination of pentamidine and allopurinol in the treatment of antimony unresponsive cases of visceral leishmaniasis.

OBJECTIVES: A randomized clinical trial of low dosage combination of pentamidine and allopurinol was carried out with objectives to assess the efficacy and toxicity as compared to full dosage of pentamidine in antimony unresponsive visceral leishmaniasis (VL) patients. METHODS: Using a randomized control clinical trial, a total of 158 antimony unresponsive patients of VL were randomly allocated into two treatment groups. Patients in one group (n=80) received half the dosage of pentamidine i.e. 2 mg/kg body weight by IM route on alternate day and allopurinol in dose of 15 mg/kg body weight in three divided dosages for 30 days; patients in the second group (n=78) received pentamidine in dose of 4 mg/kg body weight by IM route on alternate day for 15 injections in 30 days. The efficacy and safety of the two regimens were compared. RESULTS: Apparent cure i.e. clinical and pathological cure at the end of therapy, in 78 (97.5%) and 67 (86%), and ultimate cure i.e. clinical and parasitological cure at the end of follow-up of six months, in 73 (91.25%) and 58 (74.35%) patients was observed in the combination regimen and single regimen group respectively. The difference of the ultimate cure between two groups of the patients was statistically significant (p < 0.01). In single regimen group, 11 (14%) patients showed primary unresponsiveness (with no response during treatment) and nine (13%) relapse (after six months of follow-up) respectively, where as in combination regimen group, two (2.5%) patients showed primary unresponsiveness and five (6.4%) relapse respectively. By the end of the treatment, the incidence of injection-related toxicity, such as rigor and fever, was same in both groups. No hyperglycemia was observed in combination therapy probably due to reduced dose of pentamidine and three patients in single regimen developed hyperglycemia and one of them developed irreversible hyperglycemia. CONCLUSIONS: The study showed that the combination of pentamidine (half dose) and allopurinol is more effective in achieving ultimate cure with an added advantage of reduced toxicity in unresponsive cases as compared to full pentamidine dose.

Concomitância de leishmanioses e infecçäo pelo vírus da imunodeficiência humana (HIV): estudo de quatro casos / Concurrent leishmaniasis and human immunodeficiency virus infection: a study of four cases

Säo apresentados quatro casos de leishmaniose em pacientes com SIDA, sendo dois de leishmaniose visceral e dois com forma cutâneo-mucosa. Lesöes cutâneas e de mucosa oral, disseminadas, estavam presentes nos pacientes com a forma tegumentar da doença. Febre prolongada, hepatoesplenomegalia e pancitopenia foram as manifestaçöes principais da forma visceral. A contagem de linfócitos TCD4+ era baixa em todos os casos. A pesquisa de leishmanias foi positiva no aspirado de medula óssea e na biópsia de lesöes cutâneas e mucosas. Os pacientes responderam ao tratamento com antimoniais pentavalentes e com a anfotericina B. Poucos casos de coinfecçäo leishmaniose e HIV têm sido descritos em nosso meio. Apesar da ampla expansäo de ambas, até agora suas áreas de distribuiçäo geográfica teve pouca superposiçäo. Os autores recomendam a inclusäo desta parasitose no diagnóstico diferencial das doenças oportunistas que acometem indivíduos com SIDA

Diabetes mellitus associated with pentamidine isethionate in diffuse cutaneous leishmaniasis

The authors report a case of a male patient from Bacabal, MA with diffuse cutaneous leishmaniasis (DCL), for at least nine years, with 168 lesions on his body. These were tumour-like nodules with some ulceration. He used pentavalent antimonial (glucantime) and an association of gamma interferon plus glucantime with improvement of the lesions but relapsed later. Recently, pentamidine isethionate (pentacarinat) was given a dosage of 4mg/kg/weight/day on alternate days for 20 applications. After 3 months a similar course of 10 application was given 2 times. Later he developed diabetic signs with weight loss of 10kg, polydypsia, polyuria and xerostomia. The lower limbs lesions showed signs of activity. Blood glucose levels normalised and remain like this at moment. Attention is drawn to the fact that pentamidine isethionate should be used as a therapy option with care, obeying rigorous laboratory controls including a glucose tolerance test.

Pentamidina: atualizaçäo e aplicaçöes clínicas / Pentamidine: Up-to-dating and clinical use

Os autores efetuaram uma atualizaçäo sobre a pentamidina e comentam suas aplicaçöes na clínica médica

Changing response to diamidine compounds in cases of kala-azar unresponsive to antimonial.

Two hundred and forty patients of kala-azar unresponsive to antimonial were treated with pentamidines in a dose of 4 mg/kg body weight on alternate days for 20 injections. Of these, 175 were treated with pentamidine isethionate and 65 with pentamidine methane sulphonate (Lomidine). Clinical and parasitological cure were significantly higher with lomidine as compared to pentamidine isethionate. However, cardiovascular, gastrointestinal and metabolic toxicity including hyperglycaemia were more marked with lomidine. Mortality rate was also significantly (P less than .05) higher with lomidine therapy. Significantly lower clinical and parasitological cure and higher relapse rate were observed in the present study compared with an earlier study in which pentamidine was used in the same doses for 10-12 injections only.

Tratamento da leishmaniose tegumentar americana com a pentamidina, esquema em dose única endovenosa / Treatment of american cutaneous Leishmaniasis with pentamidine: scheme in single endovenous dosis

Os autores relatam os resultados obtidos no tratamento de 63 casos de leishmaniose tegumentar americana empregando o metanossulfonato de pentamidina (Lomidine) em dose única e endovenosa. Na dose de 120 a 480 mg em 100 a 250 ml de soro glicosado a 5%, a eficâcia foi de 76%. Considerando as reaçöes colaterais e as contra-indicaçöes da pentamidina, recomendam a sua utilizaçäo somente em alguns casos de recidiva ou rebeldes ao tratamento antimonial

Tratamento com pentamidina de seis casos da forma mucosa de leishmaniase tegumentar / Treatment with pentamidine of 6 cases with mucus form of tegumentary leishmaniasis

As principais razöes para a escolha da pentamidina no presente ensaio terapêutico foram a alta taxa de recidiva de casos de forma mucosa de leishmaniose tegumentar com o tratamento pelos antimoniais pentavalentes e o fato deste medicamento ter sido usado com sucesso na forma cutânea da doença. Seis pacientes com forma mucosa de leishmaniose tegumentar diagnosticados clinicamente por exame dermato-otorrinolaringológico, reaçäo intradérmica de Montenegro, cultura inoculaçäo em hamster e esfregaço de material obtido das lesöes, exame histopatológico e pesquisa de anticorpos circulantes, foram tratados com pentamidina na dose de 200 mg em dias alternados, com dose total entre 2,3 a 5,9g, de acordo com a clínica. Houve cura clínica e parasitológica de cinco casos, com acompanhamento variando de 12 a 24 meses após o tratamento. No único caso de falha, tratava-se de um paciente que também näo respondeu ao tratamento com Glucantime. Entre os efeitos colaterais estäo um caso de diabetes mellitus, alteraçöes transitórias de glicemia em dois casos e abscesso glúteo em um, concluindo-se ser boa a resposta terapêutica à pentamidina dos casos da forma mucosa de leishmaniose tegumentar

A pentamidina: excelente terapêutica da leishmaniose cutânea; esquema de tratamento idealizado na Guiana Francesa em dose única / Pentamidine: excelent therapy of cutaneous leishmaniasis: treatment schedule used in French Guiany with single-dose

Apresenta-se a experiência no tratamento da leishmaniose cutânea com a pentamidina, em vários esquemas terapêuticos, assinalando os bons resultados e a regular tolerância ao medicamento. O esquema mais prático, parece ser o da administraçäo em infusäo venosa em dose única de três a quatro ampolas (360 a 480mg). Enfatiza-se a eficácia, tolerabilidade, baixo custo e facilidade de administraçäo em regiöes distantes, onde o paciente ou a equipe médica tem dificuldade de retornar em curto período de tempo