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

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

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

A Cautionary Tale: Lack of Consistency in Allele Sizes between Two Laboratories for a Published Multilocus Microsatellite Typing System

For species with low genetic diversity, typing using the differences in PCR fragment length resulting from variations in numbers of short tandem repeats has been shown to provide a high level of discrimination. This technique has been called multilocus microsatellite typing (MLMT) or multiple-locus variable-number tandem repeat analysis, and studies usually employ genetic or sequence analyzers to size PCR fragments to a high degree of precision. We set out to validate one such system that has been developed for Aspergillus fumigatus (H. A. de Valk, J. F. G. M. Meis, I. M. Curfs, K. Muehlethaler, J. W. Mouton, and C. H. W. Klaassen, J. Clin. Microbiol. 43:4112-4120, 2005). The sizes of the alleles were compared both by sequencing and from two genotyping laboratories, where they used capillary electrophoresis (CE) for sizing. Size differences of up to 6 bases were found between the actual sizes reported by sequencing and the sizes reported by CE. In addition, because the two genotyping laboratories used different machines and running conditions, differences of up to 3 bases were identified between them. As the microsatellite markers used differ by repeat units of 3 or 4 bases, it was not possible to assign PCR fragments to the correct alleles without confirming the sizes of a range of alleles by direct sequencing. Lines of best fit were plotted for each CE machine against actual sizes and will therefore enable unsequenced PCR fragments to be assigned to the correct alleles. This study highlights the care required to ensure that an MLMT system undergoes a suitable correction procedure before data can be merged between different laboratories involved in the typing of individual species