Maria Aparecida Shikanai Yasuda

An Open-Label Comparative Pilot Study of Oral Voriconazole and Itraconazole for Long-Term Treatment of Paracoccidioidomycosis

BACKGROUND In previous studies, itraconazole was revealed to be an effective therapy and was considered to be the gold standard treatment for mild-to-moderate acute and chronic clinical forms of paracoccidioidomycosis. A pilot study was conducted to investigate the efficacy, safety, and tolerability of voriconazole for the long-term treatment of acute or chronic paracoccidioidomycosis, with itraconazole as the control treatment. METHODS A randomized, open-label study was conducted at 3 Brazilian tertiary care hospitals. Patients were randomized (at a 2 : 1 ratio) to receive oral therapy with voriconazole or itraconazole for 6 months. Patients receiving >or=1 dose of study drug were evaluated for safety; patients with confirmed paracoccidioidomycosis who completed >or=6 months of therapy (treatment-evaluable patients) were evaluated for treatment efficacy. Satisfactory global response was assessed at the end of treatment. RESULTS Fifty-three patients were evaluated for treatment safety (35 received voriconazole, and 18 received itraconazole). Both drugs were well tolerated. The most common treatment-related adverse events in the voriconazole group included abnormal vision, chromatopsia, rash, and headache; the most common treatment-related adverse events in the itraconazole group included bradycardia, diarrhea, and headache. Liver function test values were slightly higher in patients receiving voriconazole than in those receiving itraconazole; 2 patients in the voriconazole group were withdrawn from treatment because of increased liver function test values. In the intent-to-treat populations, the satisfactory response rate (i.e., complete or partial global response) was 88.6% among the voriconazole group and 94.4% among the itraconazole group. The response rate among treatment-evaluable patients was 100% for both treatment groups; no relapses were observed after 8 weeks of follow-up. CONCLUSIONS This is, to our knowledge, the first study to demonstrate that voriconazole is as well tolerated and effective as itraconazole for the long-term treatment of paracoccidioidomycosis.

Brazilian guidelines for the management of candidiasis - a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical.

Candida infections account for 80% of all fungal infections in the hospital environment, including bloodstream, urinary tract and surgical site infections. Bloodstream infections are now a major challenge for tertiary hospitals worldwide due to their high prevalence and mortality rates. The incidence of candidemia in tertiary public hospitals in Brazil is approximately 2.5 cases per 1000 hospital admissions. Due to the importance of this infection, the authors provide a review of the diversity of the genus Candida and its clinical relevance, the therapeutic options and discuss the treatment of major infections caused by Candida. Each topography is discussed with regard to epidemiological, clinical and laboratory diagnostic and therapeutic recommendations based on levels of evidence.

Cytomegalovirus infection in transplant recipients

Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.

Pharmacological management of paracoccidioidomycosis

A systemic and endemic emerging mycosis in Latin America, paracoccidioidomycosis, is characterised by its chronicity and by the severity of the disseminated form in healthy individuals, as well as in immunocompromised individuals co-infected with HIV, resulting, in the latter, in a mortality rate in the range of 30 - 45%. The long (several years) duration of treatment results from the immunosuppression induced by the disease or from the survival capacity of the fungus in tissue. A few controlled studies and case reports have shown that fast-acting azolic and sulfa derivatives are useful treatment alternatives for patients presenting milder forms of the disease. However, when using such drugs, treatment regimens of longer duration are required for the maintenance of patients with more severe forms. The search for new alternatives for treating the most severe forms is an ongoing challenge. Novel treatments may be found among new classes of drugs, drug combinations, or agents capable of modulating the immune response, such as a peptide derived from the 43-kDa Paracoccidioides brasiliensis glycoprotein.A systemic and endemic emerging mycosis in Latin America, paracoccidioidomycosis, is characterised by its chronicity and by the severity of the disseminated form in healthy individuals, as well as in immunocompromised individuals co-infected with HIV, resulting, in the latter, in a mortality rate in the range of 30 – 45%. The long (several years) duration of treatment results from the immunosuppression induced by the disease or from the survival capacity of the fungus in tissue. A few controlled studies and case reports have shown that fast-acting azolic and sulfa derivatives are useful treatment alternatives for patients presenting milder forms of the disease. H-owever, when using such drugs, treatment regimens of longer duration are required for the maintenance of patients with more severe forms. The search for new alternatives for treating the most severe forms is an ongoing challenge. Novel treatments may be found among new classes of drugs, drug combinations, or agents capable of modulating the immune response, such as a peptide derived from the 43-kDa Paracoccidioides brasiliensis glycoprotein.

The present situation, challenges, and perspectives regarding the production and utilization of effective drugs against human Chagas disease

The fi rst effective drugs against human Trypanosoma cruzi infection (nifurtimox, produced by Bayer, and benznidazole, produced by Roche) became available in the 1960s1,2. Because these drugs were initially only recommended for acute cases, the international demand for their production was very low. In the subsequent 20 years, good treatment results for chronic infection in children stimulated several studies in adults with the chronic indeterminate form of the disease and even in adults in the initial stages of chronic cardiomyopathy3,4. At the end of the twentieth century, Roche transferred the production of benznidazole to LAFEPE (Laboratório Farmacêutico de Pernambuco), a Brazilian public enterprise that received its last GMP (Certifi cate of Good Manufacturing Practice) in 20095. Because of the increased demand for the product and several problems with its production and distribution, the World Health Organization and the scientifi c community involved in research on Chagas disease have become worried in recent years about the worldwide shortage of the product, which could result in a reduced opportunity to treat millions of infected individuals6,7. The present situation can be summarized as follows:

Migração boliviana e doença de Chagas: limites na atuação do Sistema Único de Saúde brasileiro (SUS)

Migracoes acarretam mudancas nos perfis epidemiologicos, impactando sistemas de saude dos paises receptores. O Brasil atrai imigrantes que se inserem precariamente nas metropoles. Na Bolivia, a doenca de Chagas e endemica, fato relevante para o SUS brasileiro.O texto analisa a atuacao e os limites dos profissionais de saude no atendimento aos bolivianos no SUS, enfocando a doenca de Chagas, por meio de entrevistas aplicadas nos servicos primario, secundario e terciario na regiao central da cidade de Sao Paulo, principal destino dos imigrantes bolivianos. As precarias condicoes de vida dos bolivianos caracterizam iniquidades em saude. Idioma e cultura limitam a compreensao sobre o cuidado. Constata-se desconhecimento da clinica e epidemiologia da doenca de Chagas entre os profissionais que atendem esses imigrantes. Faz-se necessaria a revisao de estrategias assistenciais e de controle da doenca de Chagas.