Prospective multicentre study on azole resistance in Aspergillus isolates from surveillance cultures in haematological patients in Italy.

OBJECTIVES: This study was conducted to assess the prevalence of azole resistance in Aspergillus isolates from patients with haematological malignancies or who were undergoing haematopoietic stem cell transplantation and to identify the molecular mechanism of resistance. METHODS: In this 28-month prospective study involving 18 Italian centres, Aspergillus isolates from surveillance cultures were collected and screened for azole resistance, and mutations in the cyp51A gene were identified. Resistant isolates were genotyped by microsatellite analysis, and the allelic profiles were compared with those of resistant environmental and clinical isolates from the same geographical area that had been previously genotyped. RESULTS: There were 292 Aspergillus isolates collected from 228 patients. The isolates belonged mainly to the section Fumigati (45.9%), Nigri (20.9%), Flavi (16.8%) and Terrei (4.8%). Three isolates showed itraconazole resistance: Aspergillus fumigatus sensu stricto, Aspergillus lentulus (section Fumigati) and Aspergillus awamori (section Nigri). The itraconazole resistance rates were 1% and 1.48% considering all Aspergillus spp. isolates and the Aspergillus section Fumigati, respectively. The prevalence of azole resistance among all the patients was 1.3%. Among patients harbouring A. fumigatus sensu stricto isolates, the resistance rate was 0.79%. The A. fumigatus isolate, with the TR34/L98H mutation, was genotypically distant from the environmental and clinical strains previously genotyped. CONCLUSIONS: In this study, the Aspergillus azole resistance rate was 1% (3/292). In addition to A. fumigatus sensu stricto, A. lentulus and A. awamori azole-resistant isolates were identified. Therefore, it is important have a correct identification at the species level to address a rapid therapy better, quickly understand the shift towards cryptic species and have an updated knowledge of the local epidemiology.

Innate and adaptive immunity in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal recessive syndrome characterised by chronic mucocutaneous candidiasis (CMC) and multiple endocrine failures. While the spectrum and modalities of autoimmunity are the main objects of current research into APECED, unequivocal data on the efficiency of immune responses to infectious agents are still elusive. The in vitro ability of monocytes and polymorphonuclear leucocytes to phagocytise and kill bacteria and fungi, and the degree of activation of lymphocytes cultured with mitogens and Candida albicans were investigated by flow cytometry in 11 APECED patients and healthy subjects. In addition, a comparison of gamma-globulin and immunoglobulin (Ig) concentrations was performed, and a correlation was sought between oral fungal load and the anti-Candida antibody titre. No difference between APECED patients and healthy subjects was observed in the phagocyte function, although the patients had a larger number of monocytes. Similarly, cultured lymphocytes were equally activated in the two groups. The concentration of gamma-globulins was higher among APECED patients, and anti-Candida IgM and IgG correlated with current and past oral candidiasis respectively. APECED patients have efficient innate and adaptive immune responses against exogenous stimuli, and currently, the mechanisms of mucocutaneous anergy leading to the high prevalence of CMC in this syndrome remain to be elucidated.

Rhodotorula mucilaginosa outbreak in neonatal intensive care unit: microbiological features, clinical presentation, and analysis of related variables.

Reported here are the features of a Rhodotorula mucilaginosa outbreak that occurred in a neonatal intensive care unit. Over a period of 19 days, clinical and laboratory signs of sepsis appeared in four premature infants carrying indwelling vascular catheters. After bloodstream infection with R. mucilaginosa was ascertained, the patients underwent amphotericin B therapy and recovered completely. In a retrospective case-control study, the variables displaying a statistical difference between case and control-group neonates were birth weight, gestational age, duration of parenteral nutrition, duration of antibiotic therapy and prophylactic administration of fluconazole. To our knowledge, this is the first reported outbreak caused by yeasts of the Rhodotorula genus.

Castleman's disease with diffuse cervical localisation: case report.

Castleman's disease is a rare disorder of the lymphoid tissue with a predominantly mediastinic localisation, but possible in any lymph node or extra-lymph node site. The aetiopathogenesis remains to be defined and, in the literature, only just over 500 cases have been reported, with only 57 located in a cervical site. Clinically, a solitary or localised form and a systemic or multicentric form can be distinguished, whilst, from a histological viewpoint, this lesion may be of the hyaline vascular or plasma-cellular type. Even if all the cases localised in a cervical site have been described as a single mass, the case described herein refers to diffuse cervical lymph-node hyperplasia with histological characteristics of the hyaline-vascular type, with the presence of a plasmacellular component. Evolution, over the 7 years following diagnosis, was benign, despite the fact that the patient was not submitted to surgical treatment. The low titre of B and T4 lymphocytes would appear to indicate that Castleman's disease might be an immunological disorder, due to atypical hyperplasia of the lymphoid tissue. It is suggested that Castleman's disease, in the cervical site, be classified into two subtypes: a cervical form, presenting as a single mass, and a multicentric cervical form. Data from a review of the literature are discussed.