Rhinoorbital mucormycosis in the immunocompetent: Experience with Isavuconazole.

Mucormycosis is a severe opportunistic fungal infection caused by Mucorales. The majority of the affected patients have a history of immunosuppression, with a reported incidence of 4-19% in the immunocompetent. Early recognition and diagnosis, combined with surgical debridement and appropriate antifungal therapy are essential to achieve a cure. In this article we report the case of a 61-year-old immunocompetent male who complained with pain in his right eye. After being first diagnosed with conjunctivitis and treated accordingly, he eventually needed surgical debridement and the biopsy showed the presence of fungi of the class Zygomycetes. He was submitted to intravenous therapy with Liposomal Amphotericin B (LAmB) and Posaconazole for several days, which was then changed to Isavuconazole due to bicytopenia. He also received treatment with hyperbaric oxygen, achieving altogether good results. He was discharged after eight months, still on oral Isavuconazole 200mg/day and re-evaluated after three and six months, showing no evidence of progression of the infection.

Efavirenz concentrations in HIV-infected patients with and without viral hepatitis.

AIMS: Data on efavirenz in HIV/viral hepatitis co-infected patients is non-consensual, probably due to liver function heterogeneity in the patients included. METHODS: A case control study was performed on 27 HIV-infected patients, with controlled and homogenous markers of hepatic function, either mono-infected or co-infected with HBV/HCV, to ascertain the influence of viral hepatitis on efavirenz concentrations over a 2-year follow-up period. RESULTS: No differences were found in efavirenz concentrations between groups both during and at the end of the follow-up period: control (2.43 +/- 1.91 mg l(-1)) vs. co-infected individuals (2.37 +/- 0.37 mg l(-1)). CONCLUSION: It was concluded that HBV/HCV infections in themselves do not predispose to an overexposure to efavirenz.

[Takotsubo Cardiomyopathy: Cause of a Cardiogenic Shock]. / Miocardiopatia de Takotsubo: Na Origem do Choque Cardiogénico.

Takotsubo cardiomyopathy, of unknown etiology, is characterized by sudden and transient systolic dysfunction of the mid-apical segments of the left ventricle without significant coronary disease, and full normalization of segmental changes. More common in middle-aged women, it is cause of differential diagnosis with acute coronary syndrome. We present the case of a 59 year old woman admitted to the emergency room with sudden chest pain and dyspnea. At presentation: acute hypotensive pulmonary edema requiring aminergic support and invasive ventilation. Blood tests showed elevated necrosis myocardial enzymes. Serial electrocardiograms: sinus rhythm with progressive inversion of the T wave through the precordial leads (v2 - v6). Control echocardiograms: overall decreased systolic function with apical akinesia, and full reversal of the changes in 2 weeks. Cardiogenic shock of unknown etiology was admitted and a coronary computed tomography angiography was performed excluding coronary heart disease, supporting the diagnosis of Takotsubo cardiomyopathy.

A miocardiopatia de Takotsubo, de etiologia desconhecida, caracteriza-se pela disfunção sistólica súbita e transitória dos segmentos médio-apicais do ventrículo esquerdo, sem doença coronária significativa, com total normalização das alterações segmentares. É aais frequente em mulheres de meia-idade, implicando diagnóstico diferencial com a sindrome coronária aguda. Apresentamos o caso de uma mulher de 59 anos que recorreu ao Serviço de Urgência por dispneia súbita e dor torácica. Á admissão apresentava-se em edema pulmonar agudo hipotensivo com necessidade de suporte aminérgico e ventilação invasiva. A avaliação analítica demonstrava elevaçãodos marcadores cardíacos. Electrocardiogramas seriados em ritmo sinusal com inversão progressiva da onda T nas derivações precordiais (v2 - v6). Ecocardiogramas de controlo revelando acinésia apical com diminuição da função sistólica global, e reversão total das alterações em duas semanas. Admitido choque cardiogénico de etiologia não esclarecida foi excluída doença coronária, sustentando o diagnóstico de miocardiopatia de Takotsubo.

Intra-individual variability in efavirenz plasma concentrations supports therapeutic drug monitoring based on quarterly sampling in the first year of therapy.

Intrapatient variability in drug plasma concentrations is critical to the use of therapeutic drug monitoring with efavirenz, a non-nucleoside reverse-transcriptase inhibitor. Marked intrapatient variability, particularly for concentrations near the minimal therapeutic concentration, could be a predictor of virologic failure, meaning that a single concentration is of limited value. Previous reports on efavirenz intra-individual variability were obtained only in follow-up periods of 3 to 12 months and do not provide a rationale for the periodicity of sample measurements needed in long-term therapy to identify patients with a large variability and increased risk of therapeutic failure. The aim of this work was to investigate intra-individual variability in efavirenz plasma concentrations over a long-term follow-up period to support therapeutic drug monitoring. In a case series study, clinical and laboratory data were collected from all HIV-positive adults at the immunodeficiency outpatient clinic who were on regimens containing efavirenz in 2002 and who gave their informed consent (n = 31). Efavirenz plasma concentrations were measured throughout a 3 year period, without dose adjustments. For each patient, 6 to 12 samples were obtained over the follow-up period with an interval of at least 3 months between each sample. Mean plasma concentrations (mg/L) in the first, second, and third year of follow-up were 2.20 +/- 0.64, 2.17 +/- 0.68, and 2.31 +/- 0.57. Mean intra-individual variability throughout the first, second, and third year of study was 27%, 31%, and 25%, ranging from 12% to 63%. No differences in intrapatient variability in efavirenz plasma concentrations were found between females and males, HBV/HCV and HBV/HCV patients, or age above/below 40 years. Mean values (intra-individual variability) in plasma concentrations (mg/L) found in 3 of 31 patients who experienced virologic failure were 1.78 (42%), 1.52 (16%), and 1.68 (45%). The high interindividual variability and low maintained values of intrapatient variability in plasma concentrations support therapeutic drug monitoring, which could be based on measurements taken quarterly during the first year of therapeutics. In patients presenting high values of intra-individual variability (eg, >40%) associated with low plasma concentrations (eg, <2 mg/L), more frequent measurements over longer periods (more than 1 yr) of controlled concentrations might be recommended, but this requires further investigation.

Long-term and concentration-dependent beneficial effect of efavirenz on HDL-cholesterol in HIV-infected patients.

AIMS: To investigate the long-term effects of efavirenz on cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and triglycerides (TG). METHODS: Thirty-four HIV-infected patients who commenced efavirenz therapy were monitored for 36 months. RESULTS: In patients with baseline HDL-C<40 mg.dL-1 an increase in HDL-C from 31+/-1 mg.dL-1 to 44+/-2 mg.dL-1 (95% confidence interval 5.9, 21.9, P<0.01) was observed and remained throughout the follow-up period. Median efavirenz plasma concentration was 1.98 mg.L-1 and a direct correlation between percentage of HDL-C variation or TC/HDL-C ratio and efavirenz plasma concentrations was found. CONCLUSIONS: There is evidence of a long-term and concentration-dependent beneficial effect of efavirenz on HDL-C in HIV-infected patients.