Anidulafungin in combination with amphotericin B against Aspergillus fumigatus.

We investigated the effects of anidulafungin alone and in combination with amphotericin B against Aspergillus fumigatus. Indifference was the only type of interaction observed in vitro. Anidulafungin at 1 and 5 mg/kg of body weight/day, amphotericin B at 1 mg/kg/day, and combination therapy prolonged the survival of mice with invasive aspergillosis. Anidulafungin at 5 mg/kg/day, alone and in combination with amphotericin B, reduced the kidney fungal burden. Overall, the combination was not superior to the most active single drug.

Evaluation of the disk diffusion method compared to the microdilution method in susceptibility testing of anidulafungin against filamentous fungi.

Susceptibility testing of anidulafungin (AFG) against 32 mold isolates showed an excellent correlation between disk diffusion (DD) and broth microdilution methods. Based on our data, a 2-microg disk of AFG and a 24-h reading time might represent the best parameters for AFG DD testing against filamentous fungi.

Posaconazole against Candida glabrata isolates with various susceptibilities to fluconazole.

We investigated the in vitro activities of posaconazole (POS), fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS) against four clinical isolates of Candida glabrata with various susceptibilities to FLC (FLC MICs ranging from 1.0 to >64 microg/ml). POS MICs ranged from < or =0.03 to 0.5 microg/ml; AMB MICs ranged from 0.25 to 2.0 microg/ml, while CAS MICs ranged from 0.03 to 0.25 microg/ml. When FLC MICs increased, so did POS MICs, although we did not observe any isolate with a POS MIC greater than 0.5 mug/ml. Time-kill experiments showed that POS, FLC, and CAS were fungistatic against all isolates, while AMB at eight times the MIC was fungicidal against three out of four isolates of C. glabrata tested. Then, we investigated the activity of POS in an experimental model of disseminated candidiasis using three different isolates of C. glabrata: one susceptible to FLC (S; FLC MICs ranging from 1.0 to 4.0 microg/ml; POS MIC of < or =0.03 microg/ml), one susceptible in a dose-dependent manner (SDD; FLC MICs ranging from 32 to 64 microg/ml; POS MICs ranging from 0.125 to 0.25 microg/ml), and another one resistant to FLC (R; FLC MIC of >64 microg/ml; POS MIC of 0.5 microg/ml). FLC significantly reduced the kidney burden of mice infected with the S strain (P = 0.0070) but not of those infected with the S-DD and R strains. POS was significantly effective against all three isolates at reducing the kidney fungal burden with respect to the controls (P ranging from 0.0003 to 0.029). In conclusion, our data suggest that POS may be a useful option in the management of systemic infections caused by C. glabrata. Additionally, the new triazole may be a therapeutic option in those cases where an FLC-resistant isolate is found to retain a relatively low POS MIC.

[Surveillance of the sanitary conditions of a public swimming pool in the city of Palermo (Italy)]. / Sorveglianza igienico-sanitaria di una piscina di uso pubblico della città di Palermo (Italia).

In a previous study we evaluated the microbiological quality of water of seven pools in the city of Palermo through evaluation of bacterial indicators of faecal contamination and of protozoa (Giardia and Cryptosporidium). In this study we also searched for the presence of fungi in two swimming pools of a public swimming facility in the same city. Samples were collected from both pools, their filtration systems and floor surfaces of the facility. Chemical-physical and microbiological examination of water of the two pools have shown that quality of water depends on the concentration of residual free chlorine and on the number of bathers in the pool. The values of four microbiological parameters (bacterial load at 22 degrees C and 36 degrees C, presence of coagulase-negative Staphylococci and Pseudomonas spp.) increased with diminishing chlorine concentrations and with increasing number of pool users. Faecal bacteria, Giardia and Cryptosporidium were not found. On the other hand, various fungi were isolated from floor surfaces and pool water even in the presence of optimal chlorine concentrations. This study confirms the importance of regular maintenance of pool disinfection systems and suggests the need to search for other micro-organisms not included in the current legislation (Giardia, Cryptosporidium and fungi).

Posaconazole activity against Candida glabrata after exposure to caspofungin or amphotericin B.

We evaluated the effects of sequential therapy with caspofungin (CAS) or amphotericin B (AMB) followed by posaconazole (POS) against Candida glabrata. The susceptibilities to POS of yeast cells pre-exposed to CAS or AMB were identical to those of untreated cells as shown by standard Clinical and Laboratory Standards Institute broth dilution, cell viability, and disk diffusion methods. We then investigated the activity of sequential regimens in an experimental model of disseminated candidiasis. CAS given at 1 mg/kg/day for 2 days followed by POS at either 15 or 30 mg/kg/day significantly reduced the counts compared to the controls, but this treatment was not superior to the use of CAS alone. Also, sequential regimens with AMB given at 1 mg/kg/day for 2 days followed by POS (AMB/POS) were effective at reducing the fungal burden against the controls. In addition, AMB/POS with both doses of the triazole were significantly more effective than AMB alone. Overall, our data showed that there is no therapeutic advantage in using CAS followed by POS, whereas an induction therapy with AMB followed by a maintenance regimen with POS might be a suitable strategy in managing C. glabrata infections.

Comparison between disk diffusion and microdilution methods for determining susceptibility of clinical fungal isolates to caspofungin.

We compared the caspofungin (CAS) susceptibility testing results generated by the disk diffusion (DD) assay with the results of the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BD) reference method for 106 yeast isolates. The isolates represented 11 different fungal species, including Candida albicans (n = 50), C. parapsilosis (n = 10), C. glabrata (n = 10), C. tropicalis (n = 10), C. guillermondii (n = 6), C. rugosa (n = 5), C. krusei (n = 5), C. kefyr (n = 2), C. pelliculosa (n = 2), Saccharomyces cerevisiae (n = 3), and Geotrichum candidum (n = 3). The DD assay was performed in supplemented Mueller-Hinton agar with CAS, which was tested at concentrations of 2, 10, and 25 mug per disk. MICs and inhibition zone diameters were evaluated at 24 and 48 h. In general, the results obtained by the DD assay correlated well with those obtained by the BD method. In particular, a significant correlation between methods was observed when CAS was used at concentration of 2 mug/disk at a reading time of either 24 or 48 h.

Detection of the norovirus variants GGII.4 hunter and GGIIb/hilversum in Italian children with gastroenteritis.

Noroviruses (NoVs) are important enteric pathogens of humans. Although they exhibit an impressive genetic diversity, few NoV strains appear to predominate worldwide. Limited epidemiological data are available on NoV gastroenteritis in Italy. In this study, we assessed the prevalence of human NoV in Italian children with gastroenteritis by using a reverse-transcription nested polymerase chain reaction (RT-PCR) assay specific for the RNA-dependent RNA polymerase (RdRp) on faecal samples collected throughout the 2004 surveillance activity in Palermo, Italy. NoVs were detected in 47% of the stool samples obtained from children <5 years age, admitted to hospital with acute non-bacterial gastroenteritis. A selection of strains was further analyzed by partial sequence analysis of the RdRp gene. The strains were characterized as genogroup (GG) II and clustered into two distinct virus populations that resembled the emerging European GGIIb/Hilversum strains and the Australian Hunter GGII.4 strains. A temporal pattern of distribution of the two NoV strains was observed which was consistent with an independent circulation of two separate strains in the local population. Based on this 1-year study we concluded that NoVs were a diffuse cause of sporadic cases of acute childhood gastroenteritis and that strains of global epidemiological relevance were circulating in Palermo, Italy in 2004.

In vitro and in vivo anticryptococcal activities of a new pyrazolo-isothiazole derivative.

We investigated the activity of a pyrazolo-isothiazole derivative (G8) against Cryptococcus neoformans. A first screening test showed that G8 at 10 mg/L inhibited the growth of 14 of 15 clinical isolates tested. Killing experiments showed that fungicidal activity was achieved after 8 h of treatment with G8 at concentrations > or =10 mg/L. In a murine model of systemic cryptococcosis, G8 was effective at prolonging survival compared with the controls. Our data indicate that this new derivative has a potential therapeutic role in infections caused by C. neoformans.

Candidal carriage in the oral cavity of human immunodeficiency virus-infected subjects.

OBJECTIVES: We sought to assess asymptomatic oral carriage of Candida species and relative density in human immunodeficiency virus-infected (HIV+) subjects, as well as to determine whether yeast carriage is associated with CD4+ cell count, HIV-1 RNA quantity, gender, route of HIV transmission, antiretroviral therapy, or smoking. STUDY DESIGN: A cross-sectional analysis of oral rinses from HIV+ and healthy subjects was undertaken. Oral candidal carriage and relative species were investigated in 42 HIV+ and 41 healthy individuals, all of whom were seen at the Palermo University Department of Oral Sciences, Italy. Data were managed and analyzed by means of the computer software package StatView 5.0.1. RESULTS: Carriage rate was 61.9% and 29.3% (P =.003) among HIV+ and healthy subjects, respectively. Similarly, density carriage in the HIV+ group was found to be significantly higher than in the control group (P = .0002). Among HIV+ subjects, Candida carriage was significantly associated with smoking, whereas density was not. Oral candidal carriage and relative density were not significantly associated with the other 4 parameters evaluated. Candida albicans was the most frequently recovered species. CONCLUSIONS: Asymptomatic candidal carriage and relative density were found to be significantly higher in the oral cavity of HIV+ subjects-but not associated with CD4+ counts or HIV-1 RNA quantities.