Single high dose of liposomal amphotericin B in human immunodeficiency virus/AIDS-related disseminated histoplasmosis: A randomized trial

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (\u3e4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access

A case of spotted fever group rickettsiosis imported into the United Kingdom and treated with ciprofloxacin: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spotted fever group rickettsioses are an interesting group of infections, which are increasing in incidence worldwide.</p> <p>Case presentation</p> <p>Here we describe an imported case to the United Kingdom occurring in a patient who had recently visited Kruger National Park in South Africa – a highly endemic area for <it>Rickettsia </it>infections. Initial treatment with doxycycline failed but the patient made a prompt recovery after commencement of ciprofloxacin.</p> <p>Conclusion</p> <p>This finding raises the possibility that there are resistant strains of <it>Rickettsia </it>present.</p

Fast determination of voriconazole in oral fluid using microextractionby packed sorbent and HPLC with fluorescence detection

A fast and reliable method for the determination of voriconazole in oral fluid using microextraction by packed sorbent and liquid chromatography with fluorescence detection was developed and validated. MEPS was performed at basic pH with only 50 μL of oral fluid and the extract was injected without an evaporation step. The overall procedure, including extraction and chromatographic analysis, took only 15 min. Voriconazole and internal standard were separated on a Lichrospher RP 8ec column (250 x 4 mm, particle diameter 5 μm) eluted with a mobile phase composed of phosphate pH 2.3 (containing 0.1 % triethylamine) and acetonitrile (64:36, v/v) at a flow rate of 1.4 mL min-1 . Total run time was 11 min, with detection being performed with excitation at 254 and emission at 372 nm. The method was successfully applied to oral fluid samples, with voriconazole concentrations presenting an average of 57.6 % of those measured in paired plasma samples.Colegio de Farmacéuticos de la Provincia de Buenos Aire

PTX3-based genetic testing for risk of aspergillosis after lung transplant

[Excerpt] We read with interest the article by Wójtowicz et al [1], and would like to comment on it and to share findings from our complementary study. We have recently established genetic variation in the long pentraxin 3 (PTX3) as a major determinant of susceptibility to invasive aspergillosis (IA) after hematopoietic stem cell transplant [2]. Wójtowicz et al are the first to uncover similar findings in solid organ transplant (SOT) recipients, highlighting a potential applicability of these markers in predicting infection across patients with intrinsically different predisposing conditions (...).ESCMID -European Society of Clinical Microbiology and Infectious Diseases(undefined

Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure1

An increase in the frequency of azole-resistant Aspergillus fumigatus has emerged

Summary of Guidelines for Managing Histoplasmosis among People Living with HIV

Abstract: Histoplasmosis is a frequent fungal opportunistic infection in people living with HIV (PLHIV), associated every year to a total of 5% to 15% of AIDS-related deaths among this population. In 2020, the first global guidelines for diagnosing and managing disseminated histoplasmosis among PLHIV was published. This document recommends (1) detection of circulating Histoplasma antigens as the recommended laboratory assay to diagnose histoplasmosis among PLHIV; (2) the use of liposomal amphotericin for induction therapy in severe or moderately severe disease, followed by a maintenance therapy with itraconazole for 12 months; a shorter maintenance therapy could be considered if the patient is clinically stable and if immune status has improved; (3) antiretroviral therapy initiation as soon as possible among patients with histoplasmosis without involvement of central nervous system; and (4) that for the treatment of co-infection with histoplasmosis and tuberculosis (TB), treatment of TB should be initiated according to the World Health Organization treatment guidelines. Appropriate health education of providers, supportive supervision, and policy guidance for the care of PLHIV are required

Genetic variability of innate immunity impacts human susceptibility to fungal diseases.

AbstractFungi are a major threat in immunocompromised patients. Despite presenting similar degrees of immunosuppression, not all individuals at-risk ultimately develop fungal diseases. The traditional view of immune suppression as a key risk factor for susceptibility to fungal infections needs to be accommodated within new conceptual advances on host immunity and its relationship to fungal disease. The critical role of the immune system emphasizes the contribution of host genetic polymorphisms to fungal disease susceptibility. This review highlights the present knowledge on innate immunity genetics that associates with susceptibility to fungal diseases

Endemic Mycoses: Novel Findings for the Clinician

Endemic mycoses are difficult-to-diagnose conditions that may mimic several other diseases, particularly tuberculosis, community-acquired pneumonia, and cancer [...