ABSTRACT
BACKGROUND: Liposomal amphotericin B (L-AMB) has been used for mucosal leishmaniasis (ML), but comparative studies on L-AMB and other drugs used for the treatment of ML have not been conducted. The present study aimed to evaluate the outcome of patients with ML who were treated with L-AMB. METHODS: This is a 15-year retrospective study of Brazilian patients with a confirmed diagnosis of ML. The therapeutic options for the treatment of ML consisted of L-AMB, amphotericin B lipid complex (ABLC), deoxycholate amphotericin B (d-AMB), itraconazole, antimonial pentavalent, or pentamidine. Healing, cure rate and adverse effects (AEs) associated with the drugs used to treat this condition were analyzed. RESULTS: In 71 patients, a total of 105 treatments were evaluated. The outcome of the treatment with each drug was compared, and results showed that L-AMB was superior to other therapeutic regimens (P = 0.001; odds ratio [OR] = 4.84; 95% confidence interval [CI] = 1.78-13.17). d-AMB had worse AEs than other treatment regimens (P = 0.001, OR = 0.09; 95% CI = 0.09-0.43). Approximately 66% of the patients presented with AEs during ML treatment. Although L-AMB was less nephrotoxic than d-AMB, it was associated with acute kidney injury compared with other drugs (P <0.05). CONCLUSION: L-AMB was more effective than other therapies for the treatment of ML. However, a high incidence of toxicity was associated with its use. Therapeutic choices should be reassessed, and the development of new drugs is necessary for the treatment of ML.
Subject(s)
Amphotericin B/therapeutic use , Antiprotozoal Agents/therapeutic use , Leishmania braziliensis , Leishmaniasis, Mucocutaneous/drug therapy , Acute Kidney Injury/chemically induced , Adult , Aged , Aged, 80 and over , Amphotericin B/adverse effects , Antimony/adverse effects , Antimony/therapeutic use , Antiprotozoal Agents/adverse effects , Brazil , Cohort Studies , Deoxycholic Acid/adverse effects , Deoxycholic Acid/therapeutic use , Drug Combinations , Female , Humans , Itraconazole/adverse effects , Itraconazole/therapeutic use , Liposomes , Male , Middle Aged , Pentamidine/adverse effects , Pentamidine/therapeutic use , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: Mucosal Leishmaniasis (ML) is a difficult to treat and severe form of Leishmaniasis. In general, more than 40% of subjects with ML have therapeutic failure upon the use of pentavalent antimony (Sbv) at 20mg/kg/day during 30 days. Additionally, Sbv is a toxic drug that requires parenteral administration, and many patients will need several courses to be cured. In cases that cannot be treated or cured by Sbv, the alternative is amphotericin B, another toxic and parenteral drug. As a consequence, many ML patients will be cured only after years of disease and may present several morbidities due to the aggressiveness of the disease or toxicity related to the treatment. Areas covered: We aimed to review clinical trials with Miltefosine or Sbv associated with pentoxifylline in the treatment of ML. Expert commentary: There are few studies to define more effective and safer therapy in mucosal disease caused by Leishmania, with an urgent need to supporting and funding well designed trials. Miltefosine monotherapy, as well as pentoxifylline combined with Sbv are promising therapeutic approaches to increase the cure rate of this neglected disease.
Subject(s)
Antimony/administration & dosage , Leishmaniasis, Mucocutaneous/drug therapy , Pentoxifylline/administration & dosage , Phosphorylcholine/analogs & derivatives , Animals , Antimony/adverse effects , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/adverse effects , Drug Therapy, Combination , Humans , Leishmaniasis, Mucocutaneous/microbiology , Neglected Diseases/drug therapy , Neglected Diseases/microbiology , Pentoxifylline/adverse effects , Phosphorylcholine/administration & dosage , Phosphorylcholine/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: The treatment of cutaneous leishmaniasis (CL) caused by Leishmania braziliensis in Brazil with pentavalent antimony (Sbv) is associated with a high rate of failure, up to 45% of cases. In addition, Sbv can only administered parenterally and has important toxic effect. An effective, safe, and oral treatment for CL is required. METHODS: A randomized controlled clinical trial was conducted to compare the efficacy and safety of high-dosage oral fluconazole (6.5-8.0 mg/kg/d for 28 days) versus a standard Sbv protocol (20 mg/kg/d for 20 days) for the treatment of CL in Bahia, Brazil. RESULTS: A total of 53 subjects were included in the trial; 26 were treated with Sbv, and 27 with fluconazole. Intention-to-treat analysis showed initial cure rates (2 months after treatment) of 22.2% (6 of 27) in the fluconazole and 53.8% (14 of 26) in the Sbv group (P = .04). Six months after treatment, the final cure rate remained the same in both groups, without any relapses. The frequencies of adverse effects in the Sbv and fluconazole groups were similar, 34.6% versus 37% respectively. One patient treated with fluconazole discontinued treatment owing to malaise, headache, and moderate dizziness (Common Terminology Criteria for Adverse Events grade 2). CONCLUSIONS: Oral fluconazole at a dosage of 6.5-8 mg/kg/d for 28 days should not be considered an effective treatment for CL caused by L. braziliensisClinical Trials Registration. NCT01953744.
Subject(s)
Antiprotozoal Agents/therapeutic use , Fluconazole/therapeutic use , Leishmania braziliensis/drug effects , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/parasitology , Adolescent , Adult , Antimony/administration & dosage , Antimony/adverse effects , Antimony/therapeutic use , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/adverse effects , Brazil , Female , Fluconazole/administration & dosage , Fluconazole/adverse effects , Humans , Leishmania braziliensis/genetics , Leishmaniasis, Cutaneous/diagnosis , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum. METHODOLOGY/PRINCIPAL FINDINGS: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues. CONCLUSIONS/SIGNIFICANCE: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment.
Subject(s)
Antimony/adverse effects , Antimony/therapeutic use , Leishmania infantum/drug effects , Leishmaniasis, Visceral/drug therapy , Liposomes/therapeutic use , Animals , Antimony/administration & dosage , Ascorbic Acid/administration & dosage , Flow Cytometry , Immunophenotyping , Mice , Mice, Inbred BALB C , Parasite Load , Statistics, NonparametricABSTRACT
Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.
Subject(s)
Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Herpes Zoster/etiology , Herpesvirus 3, Human/physiology , Adult , Aged , Aged, 80 and over , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Female , Herpes Zoster/virology , Humans , Leishmaniasis, Cutaneous/drug therapy , Male , Middle Aged , Virus ActivationABSTRACT
Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Herpes Zoster/etiology , /physiology , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Herpes Zoster/virology , Leishmaniasis, Cutaneous/drug therapy , Virus ActivationABSTRACT
O tratamento para leishmaniose cutânea (LC) utilizando antimoniais foi iniciado em 1912, no Brasil. O uso da forma pentavalente (Sb5+) se iniciou na década de 1940, e apesar de ainda ser eficaz para curar a LC efeitos adversos graves podem acontecer. Outras opções de tratamento, como pentamidina e anfotericina B também são de administração parenteral. Na tentativa de reduzir os efeitos adversos dos Sb5+, esquemas terapêuticos em doses baixas já evidenciaram ser seguros no tratamento da LC no Rio de Janeiro, sejam doses de apenas 5mg Sb5+/kg/dia por 30 dias (DB), aplicação intralesional (IL) ou em esquema de uso de uma ampola três vezes por semana (2ª/4ª/6ª) até a cura clínica...
Antimony therapy was first used to treat cutaneous leishmaniasis (CL) in 1912.Pentavalent antimonial (Sb5+) compounds were introduced as leishmaniasis therapy in the 1940s and are still efficient in curing CL, but they may cause serious adverse effects. Although there are other options for CL treatment, such as pentamidine and amphotericin B, similar to Sb5+, these drugs are also administered parenterally. To reduce the adverse effects of antimony, low-dose therapies were attempted and were proven safe in curing CL in patients in the state of Rio de Janeiro. Different schedules as 5mgSb5+/day/30 days (LowD), intralesional therapy (IL), or use of one ampoule three-times-a-week until clinical cure were proven to be efficient to cure CL...
Subject(s)
Humans , Antimony/adverse effects , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/epidemiology , Small Doses , Enzyme-Linked Immunosorbent AssayABSTRACT
BACKGROUND: Cutaneous leishmaniasis is an ultimately self-curing disease for which systemic therapy with pentavalent antimony (Sb) is effective but with side effects. We evaluated 2 local treatments, intralesional (IL) Sb and cryotherapy, for single lesions due to Bolivian Leishmania (v.) braziliensis in a placebo-controlled study. METHODS: Patients were randomized between IL Sb (650 µg/mm(2) of lesion area on days 1, 3, and 5), cryotherapy (days 1 and 14), and placebo cream (daily for 20 days) in a 3:2:3 allocation. Lesion area was measured prior to therapy, and at 1, 3, and 6 months after therapy. The criteria for lesion cure were as follows: not doubling in size at 1 month, at least 50% diminution in size at 3 months, and complete reepithelialization at 6 months. Local adverse effects were recorded. RESULTS: Cure rates were 21 of 30 (70%; 95% confidence interval [CI], 52%-83%) for IL Sb, 4 of 20 (20%; 95% CI, 8%-42%) for cryotherapy, and 5 of 30 (17%; 95% CI, 7%-34%) for placebo cream (P < .001 for IL Sb vs each other group). IL Sb adverse events were limited to injection site pain, with a mean value of 1.0 (mild). CONCLUSIONS: The comparative cure rate, small amount of drug administered, and tolerance data for IL Sb suggest that if local therapy for single L. braziliensis lesions is chosen, this treatment is attractive. Given the difficulties of performing placebo-controlled trials in the New World, the combined placebo and cryotherapy cure rate (18%; 95% CI, 10%-31%) is likely to become the standard against which future interventions for L. braziliensis are compared. CLINICAL TRIALS REGISTRATION: NCT01300975.
Subject(s)
Antimony/administration & dosage , Antiprotozoal Agents/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Administration, Topical , Adolescent , Adult , Aged , Aged, 80 and over , Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Bolivia , Child , Cryotherapy , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Leishmania braziliensis/drug effects , Leishmania braziliensis/isolation & purification , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Cutaneous/pathology , Male , Middle Aged , Placebos/administration & dosage , Treatment Outcome , Young AdultABSTRACT
INTRODUCTION: Governador Valadares is an endemic area of American tegumentary leishmaniasis (ATL). The detection rate was 15.36 per 100,000 habitants from 2001 to 2006 (Miranda, 2008). This study aimed to analyze the effects of age on the frequency of adverse reactions caused by antimony in the treatment of ATL in the City of Governador Valadares, State of Minas Gerais, Brazil, during 2009. METHODS: Data were collected from the forms of the Information System for Notifiable Diseases, and from charts, questionnaires, and home visits to patients. RESULTS: The study included 40 patients, 26 (65%) of whom were males. Individuals over the age of 50 had a 66% higher rate of adverse effects than subjects who were 50 years old or less (CI 95%, 1.14-2.41). The average age of individuals who reported some type of adverse effect was 44.11 years (SD = 20.14), while the average age of the group that did not report any adverse effect was of 25.46 years (SD = 18.37; p < 0.01). Clinical healing was 67.5%, and 10% of patients discontinued the treatment. CONCLUSIONS: In the treatment of ATL, the age of patients should be considered, because most adverse reactions occur in individuals over 50 years of age. For this reason, the drug should be used with restriction in these cases.
Subject(s)
Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Leishmaniasis, Cutaneous/drug therapy , Adolescent , Adult , Age Factors , Aged , Brazil/epidemiology , Child , Female , Humans , Leishmaniasis, Cutaneous/diagnosis , Logistic Models , Male , Middle Aged , Socioeconomic Factors , Surveys and Questionnaires , Wound Healing/drug effects , Young AdultABSTRACT
INTRODUCTION: Governador Valadares is an endemic area of American tegumentary leishmaniasis (ATL). The detection rate was 15.36 per 100,000 habitants from 2001 to 2006 (Miranda, 2008). This study aimed to analyze the effects of age on the frequency of adverse reactions caused by antimony in the treatment of ATL in the City of Governador Valadares, State of Minas Gerais, Brazil, during 2009. METHODS: Data were collected from the forms of the Information System for Notifiable Diseases, and from charts, questionnaires, and home visits to patients. RESULTS: The study included 40 patients, 26 (65%) of whom were males. Individuals over the age of 50 had a 66% higher rate of adverse effects than subjects who were 50 years old or less (CI 95%, 1.14-2.41). The average age of individuals who reported some type of adverse effect was 44.11 years (SD = 20.14), while the average age of the group that did not report any adverse effect was of 25.46 years (SD = 18.37; p < 0.01). Clinical healing was 67.5%, and 10% of patients discontinued the treatment. CONCLUSIONS: In the treatment of ATL, the age of patients should be considered, because most adverse reactions occur in individuals over 50 years of age. For this reason, the drug should be used with restriction in these cases.
INTRODUÇÃO: Governador Valadares constitui uma área endêmica de leshmaniose tegumentar americana (LTA) e o coeficiente de detecção foi de 15,36/100.000 habitantes no período de 2001 a 2006 (Miranda, 2008). Este estudo teve como objetivo analisar o efeito da idade na frequência das reações adversas provocadas pelo antimônio no tratamento de pacientes com LTA, em Governador Valadares, Estado de Minas Gerais, Brasil, no período de janeiro a dezembro de 2009. MÉTODOS: Para coleta de dados foram utilizados: ficha de notificação do Sistema de Informação de Agravos de Notificação (SINAN), prontuários, questionário e visitas domiciliares aos pacientes. RESULTADOS: Participaram do estudo 40 pacientes, sendo 26 (65%) do sexo masculino. Os indivíduos acima de 50 anos de idade tiveram prevalência 66% maior de reações adversas que as pessoas com idade de 50 ou menos (IC 95% -1,14-2,41). A média de idade dos indivíduos que relataram algum tipo de reação adversa foi de 44,11 anos (DP=20,14), enquanto no grupo que não relatou reação adversa, a média de idade foi de 25,46 anos (DP=18,37) e p < 0,01. A cura clínica foi de 67,5% e 10% dos pacientes abandonaram o tratamento. CONCLUSÕES: No tratamento da LTA, a idade do paciente deve ser considerada; pois ocorrem mais reações adversas em indivíduos acima de 50 anos de idade, que nesses casos o medicamento deve ser utilizado com restrição.
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Leishmaniasis, Cutaneous/drug therapy , Age Factors , Brazil/epidemiology , Logistic Models , Leishmaniasis, Cutaneous/diagnosis , Socioeconomic Factors , Surveys and Questionnaires , Wound Healing/drug effectsABSTRACT
For over 60 years, pentavalent antimony (Sb(v)) has been the first-line treatment of leishmaniasis. Sickle cell anemia is a disease caused by a defect in red blood cells, which among other things can cause vasooclusive crisis. We report the case of a 6-year-old child with leishmaniasis who during treatment with meglumine antimoniate developed a sickle cell crisis (SCC). No previous reports describing the relationship between antimonial drugs and sickle cell disease were found. Reviews of both the pathophysiology of SCC and the mechanism of action of Sb(v) revealed that a common pathway (glutathione) may have resulted in the SCC. ChemoText, a novel database created to predict chemical-protein-disease interactions, was used to perform a more expansive and systematic review that was able to support the association between glutathione, Sb(v), and SCC. Although suggestive evidence to support the hypothesis, additional research at the bench would be needed to prove Sb(v) caused the SCC.
Subject(s)
Anemia, Sickle Cell/chemically induced , Antimony/adverse effects , Meglumine/adverse effects , Organometallic Compounds/adverse effects , Anemia, Sickle Cell/complications , Child , Glutathione/metabolism , Humans , Leishmaniasis/complications , Leishmaniasis/drug therapy , Male , Meglumine/therapeutic use , Meglumine Antimoniate , Organometallic Compounds/therapeutic useABSTRACT
Pentavalent antimonials are first-line drugs for the treatment of the cutaneous form of American tegumentary leishmaniasis. Second-line drugs include amphotericin B and pentamidine. Although these drugs have been used for decades, there are no systematic reviews about their safety. The objective of this review was to identify and classify the main adverse effects associated with these drugs and to estimate the frequency of these effects, whenever possible. Intervention studies, case series and case reports containing information regarding clinical, laboratory or electrocardiographic adverse effects of drugs used for the treatment of cutaneous leishmaniasis were systematically retrieved from 10 databases searched between August 13, 2008 and March 31, 2009. The 65 studies included in this review had treated a total of 4359 patients from 12 countries infected with eight different Leishmania species. Despite the small number of drugs used in these studies, a wide variability in the therapeutic regimens was observed. As a consequence, the adverse effects of pentavalent antimonials and pentamidine needed to be classified jointly according to system, irrespective of formulation, daily dose, duration of treatment, and route of administration. The frequencies of adverse effects were calculated based on the data of 32 articles involving 1866 patients. The most frequently reported clinical adverse effects of pentavalent antimonials and pentamidine were musculoskeletal pain, gastrointestinal disturbances, and mild to moderate headache. Electrocardiographic QTc interval prolongation and a mild to moderate increase in liver and pancreatic enzymes were additional adverse effects of pentavalent antimonials. Patients treated with liposomal amphotericin B had mild dyspnea and erythema. The adverse effects associated with miltefosine were vomiting, nausea, kinetosis, headache, diarrhea, and a mild to moderate increase in aminotransferases and creatinine. Although closer surveillance is needed for the treatment of cutaneous leishmaniasis, antileishmanial drugs are basically safe and severe side effects requiring the discontinuation of treatment are relatively uncommon.
Subject(s)
Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Leishmaniasis, Cutaneous/drug therapy , Amphotericin B/administration & dosage , Amphotericin B/adverse effects , Antimony/administration & dosage , Antimony/adverse effects , Drug-Related Side Effects and Adverse Reactions/pathology , Humans , Incidence , Pentamidine/administration & dosage , Pentamidine/adverse effectsABSTRACT
The objective of the paper was to evaluate the influence of antimony (5+) on electrocardiographic changes in children with visceral leishmaniasis. The study was based on weekly ECGs analysis of 87 children treated, from April 2001 to May 2006, with antimoniate N-methyl glucamine. Eligible subjects included children from 6 months to 12 years of age with weight of 6-34 kg. Forty-five children (52%) were males and forty-two (48%) were females. The cardiac response to antimony was significantly milder compared to the adult populations, so the usage of meglumine antimoniate is safer. Thus, during treatment sinus rhythm was maintained without ectopic beats. No changes were observed in the P wave and in PR interval. The QRS complex remained unaltered during the treatment, the amplitude being increased. The Sokolow's indexes exceeded normal values in one child on the first week and in eight children on the fourth. The prolongation of QTc occurred in ten patients. The T wave flattening was observed in seven children on the first week. In total, ECG abnormalities were detected in 34.4% of treatment courses, while in adults they were reported in 53.8%. Antimony therapy needs ECG monitoring of the cardiac function in order to prevent complications.
Subject(s)
Antimony/adverse effects , Cardiovascular Abnormalities/chemically induced , Electrocardiography/methods , Leishmaniasis, Visceral/drug therapy , Antimony/therapeutic use , Antiprotozoal Agents/adverse effects , Antiprotozoal Agents/therapeutic use , Child , Child, Preschool , Female , Humans , Infant , Male , Meglumine/adverse effects , Meglumine/therapeutic use , Meglumine Antimoniate , Organometallic Compounds/adverse effects , Organometallic Compounds/therapeutic useABSTRACT
Introdução: Estudos têm demonstrado que a Leishmania sp. causa glomerulonefrites mesangial, membranoproliferativa focal e difusa, e nefrite intersticial. Estas alterações podem levar à ocorrência de proteinúria, alterações do sedimento urinário e perda da função renal. Como medicação de primeira escolha para o tratamento de LVA é recomendado o antimonial pentavalente, que possui boa eficácia, mas apresenta riscos de cardiotoxicidade, nefrotoxicidade e hepatotoxicidade. A Anfotecina B é utilizada como segunda escolha, mas esta droga também é nefrotóxica. O objetivo do presente trabalho é relatar o comprometimento da função renal em um paciente com diagnóstico de LVA, e que desenvolveu pancreatite após o tratamento com glucantime e apresentou melhoras nesse quadro após uso de anfotericina B, apresentando, porém, um quadro de nefrotoxicidade devido ao uso da segunda droga. Materiais e metodologia: Estudo retrospectivo de prontuário do caso de um paciente do sexo masculino, 64 anos, com diagnóstico de leishmaniose visceral. Na admissão apresentava creatinina sérica de 1,2mg/dL, uréia de 30 mg/dL, potássio de 4,6 mEq/L, proteinúria de 3+ e hematúria com 10 hemácias/campo. Após o tratamento com glucantime houve redução dos níveis de creatinina e desaparecimento da proteinúria. Porém, houve o aparecimento de pancreatite, com amilase 351mg/dL e lipase 1421 mg/dL. Devido a este efeito adverso, desencadeado pelo antimonial, foi utilizada a anfotericina B, que provocou uma piora da função renal, com creatinina 1,8 mg/dL. Após ajuste do intervalo entre as doses de anfotericina B houve normalização da função renal. Este caso ilustra os efeitos adversos relacionados ao tratamento da LVA. Conclusão: É necessário instituir um monitoramento laboratorial sistematizado da função renal e dos níveis séricos da amilase/lipase em pacientes que estejam sob tratamento de leishmaniose com antimonial pentavalente ou anfotericina B.
Introdution: Studies have shown that Leishmania sp causes glomurelonephritis characterized by mesangialcell proliferation, focal and diffuse membranoproliferative glomerulonephrittis and interstitial nephritis. These alterations may lead to the occurrence of proteinurea, alterations in urinary sedimentation and loss of renalfunction. Pentavalent antimoniate is recommended as a first choice in the treatment of AVL; this drug isefficient, but it presents the risk of cardiotoxicity, nephrotoxicity and hepatotoxicity. Amphotericin B is used as a second choice drug, but it is also nephrotoxic and may cause reactions. The objective of the present report is to demonstrate the impairment of renal function in a patient with visceral leishmaniasis who developed pancreatitis after treatment with glucantime and improved after treatment with amphotericin B, presenting, however, a case of nephrotoxicity due to the use of this second drug. Materials and methods: We report acase of a 64 year-old male patient, diagnosed with visceral leishmaniasis. On admission the patient presented creatinine 1.2mg/dL, urea 30 mg/dL, potassium 4.6 mEq/L, proteinurea 3+ and hematuria 10/field. After treatment with antimoniate a decrease in creatinine levels and the disappearance of proteinurea were observed; however, the patient developed pancreatitis, and an increase in the levels of amylase 351 mg/dL and lipase 1421 mg/dLwas verified. Due to this adverse effect triggered by the antimonial, amphotericin B was used, which provokeda worsening of the renal function, with creatinine 1.8mg/dL. After adjusting the interval between doses of amphotericin B, renal function returned to normality. This case illustrates the adverse effects related to the treatment of AVL. Conclusion: There must be a laboratorial follow up of the renal function and sera levels of amylase and lipase in patients under treatment with pentavalente antimoniate or anfotericin B.
Subject(s)
Humans , Male , Middle Aged , Amphotericin B/adverse effects , Antimony/adverse effects , Leishmaniasis, Visceral/drug therapy , Pancreatitis/chemically induced , KidneyABSTRACT
A case is reported of a 19-year-old woman, at week 24 of gestation, with visceral leishmaniosis. She was treated with meglumine antimoniate at a dose of 850 mg/day for 20 days. There occurred premature birth on day five of treatment and the neonate died one day after birth. Considering the importance of protozoiasis in our population and the rarity of the association with pregnancy, we resolved to publish the case.
Subject(s)
Abortion, Spontaneous/chemically induced , Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Leishmaniasis, Visceral/drug therapy , Meglumine/adverse effects , Pregnancy Complications, Parasitic/drug therapy , Adult , Female , Fetal Death/chemically induced , Humans , Leishmaniasis, Visceral/diagnosis , Pregnancy , Pregnancy Complications, Parasitic/diagnosisABSTRACT
Although treatment of visceral leishmaniasis with pentavalent antimony is usually successful, some patients require second-line drug therapy, most commonly with amphotericin B. To identify the clinical characteristics that predict an inadequate response to pentavalent antimony, a case-control study was undertaken in Teresina, Piaui, Brazil. Over a two-year period, there were 19 cases of VL in which the staff physicians of a hospital prescribed second-line therapy with amphotericin B after determining that treatment with pentavalent antimony had failed. The control group consisted of 97 patients that were successfully treated with pentavalent antimony. A chart review using univariate and multivariate analysis was performed. The cure rate was 90 percent with amphotericin B. The odds ratio for the prescription of amphotericin B was 10.2 for children less than one year old, compared with individuals aged over 10 years. Patients who presented coinfection had an OR of 7.1 while those on antibiotics had an OR of 2.8. These data support either undertaking a longer course of therapy with pentavalent antimony for children or using amphotericin B as a first-line agent for children and individuals with coinfections. It also suggests that chemoprophylaxis directed toward bacterial coinfection in small children with VL may be indicated
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Amphotericin B/therapeutic use , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Leishmaniasis, Visceral/drug therapy , Antimony/adverse effects , Case-Control Studies , Treatment FailureABSTRACT
Although treatment of visceral leishmaniasis with pentavalent antimony is usually successful, some patients require second-line drug therapy, most commonly with amphotericin B. To identify the clinical characteristics that predict an inadequate response to pentavalent antimony, a case-control study was undertaken in Teresina, Piaui, Brazil. Over a two-year period, there were 19 cases of VL in which the staff physicians of a hospital prescribed second-line therapy with amphotericin B after determining that treatment with pentavalent antimony had failed. The control group consisted of 97 patients that were successfully treated with pentavalent antimony. A chart review using univariate and multivariate analysis was performed. The cure rate was 90% with amphotericin B. The odds ratio for the prescription of amphotericin B was 10.2 for children less than one year old, compared with individuals aged over 10 years. Patients who presented coinfection had an OR of 7.1 while those on antibiotics had an OR of 2.8. These data support either undertaking a longer course of therapy with pentavalent antimony for children or using amphotericin B as a first-line agent for children and individuals with coinfections. It also suggests that chemoprophylaxis directed toward bacterial coinfection in small children with VL may be indicated.
Subject(s)
Amphotericin B/therapeutic use , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Leishmaniasis, Visceral/drug therapy , Adolescent , Adult , Antimony/adverse effects , Case-Control Studies , Child , Child, Preschool , Female , Humans , Infant , Male , Treatment FailureABSTRACT
Efficacy and safety of meglumine antimoniate and sodium stibogluconate BP 88R were compared in cutaneous leishmaniasis treatment in Corte de Pedra, Bahia, an endemic area of leishmaniasis due to Leishmania (Viannia) braziliensis. An open trial was developed with one hundred twenty seven patients who were diagnosed based on clinical criteria and Montenegro's skin test. Fifty eight patients were treated with meglumine antimoniate and 69 received sodium stibogluconate. Both groups received 20 mg/Sbv/kg/day for 20 days. Patients were followed every ten days during treatment and every month thereafter for three months. Sixty two percent patients cured with meglumine antimoniate and 55% cured with sodium stibogluconate (p = 0.42). Headache was more frequent during the first half of treatment in patients receiving sodium stibogluconate (p = 0.026). During the second half, patients treated with sodium stibogluconate showed a greater frequency of myalgia/arthralgia (p = 0.004) and abdominal pain/anorexia (p = 0.004). Three patients treated with sodium stibogluconate had severe side effects.
Subject(s)
Antimony Sodium Gluconate/therapeutic use , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Leishmania braziliensis , Leishmaniasis, Cutaneous/drug therapy , Meglumine/therapeutic use , Organometallic Compounds/therapeutic use , Adolescent , Adult , Animals , Antimony/adverse effects , Antimony Sodium Gluconate/adverse effects , Antiprotozoal Agents/adverse effects , Chi-Square Distribution , Child , Female , Humans , Male , Meglumine/adverse effects , Meglumine Antimoniate , Middle Aged , Organometallic Compounds/adverse effectsABSTRACT
Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.
The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.
Subject(s)
Adolescent , Adult , Animals , Humans , Middle Aged , Antimony/administration & dosage , Antimony/adverse effects , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/adverse effects , Organometallic Compounds/administration & dosage , Leishmania braziliensis , Leishmaniasis, Mucocutaneous/drug therapy , Meglumine/administration & dosage , Meglumine/adverse effects , Kidney/drug effects , Organometallic Compounds/adverse effects , Drug Evaluation , Drug Tolerance , Leishmaniasis, Mucocutaneous/physiopathology , Prospective Studies , Kidney/physiopathology , Time FactorsABSTRACT
Twenty-three patients from Rio de Janeiro, Brazil-an area of Leishmania (Viannia) braziliensis transmission-were randomly assigned to receive either a high dose (20 mg/kg/day) of antimony or a lower one (5 mg/kg/day) in a 30 days series. The two treatment regimens showed similar responses. In 10 out of 12 patients receiving a dose of 5 mg/kg/day and 9 out of 11 patients with a dosage of 20 mg/kg/day a complete epithelization was noted by the end of treatment. In addition patients were followed for up to 7 years. No reactivation or development of mucosal lesions were observed in both groups during the extensive follow-up. We think that a low dosage of antimony could be equally effective than a higher one, at least in the presence of the clinical picture usually seen in Rio de Janeiro.