Fungal prostatitis: an update.

Prostate pathology is a daily occurrence in urological and general medical consultations. Besides hyperplasia and neoplastic pathology, other processes, such as infectious ones, are also documented. Their etiology is diverse and varied. Within the infectious prostatic processes, fungi can also be a specific cause of prostatitis. Fungal prostatitis often appears in patients with impaired immunity and can also be rarely found in healthy patients. It can result from a disseminated infection, but it can also be localized. Fungal prostatitis is a nonspecific and harmless process. Diagnosis is commonly made by fine needle aspiration cytology or by biopsy. A number of fungi can be involved. Although there are not many reported cases, they are becoming more frequent, in particular in patients with some degree of immunodeficiency or those who live in areas where specific fungi are endemic or in visitors of those areas. We present a comprehensive review of the various forms of fungal prostatitis, and we describe the morphological characteristics of the fungi more frequently reported as causes of fungal prostatitis. We also report our own experience, aiming to alert physicians, urologists and pathologists of these particular infections.

Assessing micafungin/triazole combinations for the treatment of invasive scedosporiosis due to Scedosporium apiospermum and Scedosporium boydii.

OBJECTIVES: Scedosporium infections are associated with high therapeutic failure rates. Combination therapy may be an alternative approach to improve outcome. The in vitro and in vivo efficacy of micafungin plus posaconazole or plus voriconazole was investigated herein. METHODS: Scedosporium boydii (n = 17) and Scedosporium apiospermum (n = 26) were tested using the chequerboard method according to CLSI M38-A2 guidelines and the fractional inhibitory concentration index (FICI) was evaluated. In vivo outcome of micafungin plus posaconazole or micafungin plus voriconazole against two isolates of each of the mentioned species was evaluated in a well-established, immunocompromised, haematogenous murine model of systemic scedosporiosis. Survival and tissue burden in kidneys and brain were investigated. RESULTS: The FICI category of 'no interaction' was most frequent, while 'synergism' or 'antagonism' was rarely observed. FICI failed to predict the in vivo outcome of both combinatorial treatment strategies. In vivo outcome was strain-dependent rather than species-dependent, even though effects on fungal tissue burden were more pronounced for S. boydii. Both combinations improved survival significantly when compared with untreated controls and micafungin monotherapy. Voriconazole and posaconazole did not differ in their efficacy and micafungin failed to be effective. Combinations were by trend better than voriconazole and posaconazole as single therapy, but statistically significant differences were lacking. CONCLUSIONS: No benefit of the azole/echinocandin combination was found when compared with voriconazole and posaconazole monotherapies. FICI failed to predict the outcome of in vivo drug combinations in the murine study.

Combination therapy in the treatment of experimental invasive fungal infection by Sarocladium (Acremonium) kiliense.

Since human infections by Sarocladium (Acremonium) kiliense are usually refractory to antifungal therapy, combinations of drugs are an option that needs exploring. The antifungal activities of anidulafungin plus posaconazole or voriconazole and of amphotericin B plus voriconazole were evaluated and their efficacy was tested in a murine model of disseminated infection by three S. kiliense strains. The results showed that although efficacy was strain-dependent, these combinations work better, in general, than monotherapies. The best results were obtained with the combination of anidulafungin plus posaconazole, although the in vitro assay showed indifference or an antagonistic effect.

In vitro antifungal susceptibility of Candida glabrata to caspofungin and the presence of FKS mutations correlate with treatment response in an immunocompromised murine model of invasive infection.

It has been argued that the in vitro activity of caspofungin (CSP) is not a good predictor of the outcome of echinocandin treatment in vivo. We evaluated the in vitro activity of CSP and the presence of FKS mutations in the hot spot 1 (HS1) region of the FKS1 and FKS2 genes in 17 Candida glabrata strains with a wide range of MICs. The efficacy of CSP against systemic infections from each of the 17 strains was evaluated in a murine model. No HS1 mutations were found in the eight strains showing MICs for CSP of ≤ 0.5 µg/ml, but they were present in eight of the nine strains with MICs of ≥ 1 µg/ml, i.e., three in the FKS1 gene and five in the FKS2 gene. CSP was effective for treating mice infected with strains with MICs of ≤ 0.5 µg/ml, showed variable efficacy in animals challenged with strains with MICs of 1 µg/ml, and did not work in those with strains with MICs of >1 µg/ml. In addition, mutations, including one reported for the first time, were found outside the HS1 region in the FKS2 gene of six strains with different MICs, but their presence did not influence drug efficacy. The in vitro activity of CSP was compared with that of another echinocandin, anidulafungin, suggesting that the MICs of both drugs, as well as mutations in the HS1 regions of the FKS1 and FKS2 genes, are predictive of outcome.

Experimental murine acremoniosis: an emerging opportunistic human infection.

Acremonium is an emerging fungal pathogen causing severe infections. We evaluated the virulence of three clinically relevant species within the genus, i.e., Acremonium kiliense (currently Sarocladium kiliense), Acremonium sclerotigenum-A. egyptiacum complex and Acremonium implicatum in a murine model of disseminated infection. Both immunocompetent and immunosuppresssed mice were infected with two inocula concentrations (2 × 10(6) and 2 × 10(8) conidia/animal) of two strains of each species. Tissue burden, mortality rate, histopathology and levels of (1→3)-ß-D-glucan were used as virulence markers. None of the species of Acremonium tested was able to cause infection in immunocompetent mice. Conversely, severe infections were produced in immunocompromised mice, the spleen being the most affected organ. In general, the virulence of the Acremonium species tested was low, S. kiliense being the most virulent species.

Modest efficacy of voriconazole against murine infections by Sporothrix schenckii and lack of efficacy against Sporothrix brasiliensis.

The efficacy of voriconazole (VRC) was evaluated against two strains of each of the two most common species causing sporotrichosis, Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, using a murine model of disseminated infection. Voriconazole was administered at doses of 20 or 40 mg kg(-1) per day by gavage. The drug showed some efficacy, especially at 40 mg kg(-1) per day, in prolonging the survival and reducing fungal load in spleen and liver in mice infected with S. schenckii, whereas in animals infected with S. brasiliensis the drug did not work.

Evaluation of the efficacies of Amphotericin B, Posaconazole, Voriconazole, and Anidulafungin in a murine disseminated infection by the emerging opportunistic Fungus Sarocladium (Acremonium) kiliense.

We evaluated and compared the efficacies of different antifungal drugs against Sarocladium kiliense (formerly Acremonium kiliense), a clinically relevant opportunistic fungus, in a murine model of systemic infection. Three clinical strains of this fungus were tested, and the therapy administered was as follows: posaconazole at 20 mg/kg of body weight (twice daily), voriconazole at 40 mg/kg, anidulafungin at 10 mg/kg, or amphotericin B at 0.8 mg/kg. The efficacy was evaluated by prolonged animal survival, tissue burden reduction, and (1→3)-ß-d-glucan serum levels. In general, the four antifungal drugs showed high MICs and poor in vitro activity. The efficacy of the different treatments was only modest, since survival rates were never higher than 40% and no drug was able to reduce fungal load in all the organs for the three strains tested. Posaconazole, in spite of its high MICs (≥16 µg/ml), showed the highest efficacy. The (1→3)-ß-d-glucan serum levels were equally reduced by all drugs evaluated.

Efficacy of posaconazole in murine experimental sporotrichosis.

We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.