In vivo efficacy of voriconazole and posaconazole therapy in a novel invertebrate model of Aspergillus fumigatus infection.

The emergence of azole resistance in Aspergillus fumigatus is a clinically important issue in the management of invasive aspergillosis as it could limit therapeutic options. Accurate measurement of in vitro antifungal activity in terms of minimum inhibitory concentration (MIC) is considered of clinical relevance and often gives useful therapeutic information for physicians. However, the lack of in vitro-in vivo correlation is frequent and the observed in vitro phenotype does not always correlate with the in vivo response. In this regard, a wild-type strain and five A. fumigatus cyp51A mutated strains showing different azole susceptibility profiles were used to investigate whether the greater wax moth (Galleria mellonella) is an alternative model to assess the in vivo efficacy of voriconazole and posaconazole. Administration of both azoles improved the survival of larvae infected with susceptible strains. However, those larvae infected with resistant strains did not respond to treatment. The phenotype observed in vitro was found to correlate with the efficacy observed in vivo. Moreover, using this in vivo model, the pharmacodynamic target predicting therapeutic success (AUC(0-24)/MIC) was in the same range as previously described, allowing the use of the G. mellonella model to predict the azole susceptibility profile of A. fumigatus strains.

Detection and characterization of Enterobacteriaceae producing metallo-beta-lactamases in a tertiary-care hospital in Spain.

Carbapenem-resistant or intermediate (MIC >or=1 mg/L) clinical isolates (n = 12) of three species of Enterobacteriaceae (Klebsiella pneumoniae, Klebsiella oxytoca and Escherichia coli) were characterized. The isolates harboured integrons containing the VIM-1 metallo-beta-lactamase gene together with other resistance gene cassettes. In particular, the CTX-M-2 gene was detected in four of the K. pneumoniae isolates. The patient population was mostly paediatric and characterized by severe underlying illnesses that involved long-term hospitalization, major surgery and/or immunosuppressive and broad-spectrum antibiotic therapy.

Phyllodes tumors of the breast.

The aim of this study was to describe the clinical, mammographic, and sonographic findings of phyllodes tumor of the breast and correlate them to the benign or malignant pathological nature of the lesion and its clinical behavior. We retrospectively reviewed the clinical, radiologic, and pathologic findings of 12 cases of phyllodes tumors diagnosed in our hospital in the past 6 years, 6 of which were malignant. The surgical management and clinical course of the patients were also reviewed. Mammographically, soft tissue masses ranging from 2.5 to 15 cm were present in all patients. One patient had a mixed fat and water density mass and 2 patients had masses associated with coarse calcifications. At sonography, all tumors were well circumscribed; two of them were homogeneously hypoechoic, and the rest had heterogeneous internal echoes. Eight patients showed internal cystic areas. None of these characteristics proved to be useful in ascertaining the benign or malignant nature of the tumor. At surgery, 5 patients underwent mastectomy and 7 patients local excision of the tumor. Three of the later tumors, one benign and two malignant, recurred after several months. Fine-needle aspiration biopsy suggested the diagnosis of phyllodes tumor in only 3 cases. After surgery, six tumors were classified as benign and six as malignant, three of which being of low-grade malignancy. None of the clinical or radiologic characteristics of the tumors were useful in predicting their histological nature or their behavior after surgery. Preoperative fine-needle aspiration biopsy often misdiagnosed the tumor as benign fibroadenoma. Only the histopathologic features of the excised mass proved to be helpful in assessing malignancy.