In vitro activities of voriconazole (UK-109, 496), fluconazole, itraconazole and amphotericin B against 132 non-albicans bloodstream yeast isolates (CANARI study).

The aim was to evaluate the in vitro activity of voriconazole compared with those of amphotericin B, itraconazole and fluconazole against 132 bloodstream isolates of Candida non-albicans and Saccharomyces cerevisiae species. The minimal inhibitory concentrations (MICs) were determined by an adapted National Committee for Clinical Laboratory Standards (NCCLS) M27-A method using RPMI 1640 as test medium supplemented with 2% glucose. MIC end-points were determined with a spectrophotometer after incubation for 48 h at 35 degrees C. Optical density data were used for the calculation of the MIC end-points. For amphotericin B, the end-point was defined as the minimal antifungal concentration that exerts 90% inhibition compared with the control well growth. For the azoles, the end-points were determined at 50% inhibition of growth. Amphotericin B is highly active with 97% of isolates inhibited by < or =1 microg ml(-1). Decreased susceptibility or resistance to fluconazole was the rule among C. krusei, which is intrinsically resistant to fluconazole. For C. glabrata isolates, resistance to fluconazole and itraconazole was measured in 13% and 17% of the isolates respectively. Voriconazole was quite active in vitro against all the isolates with a MIC90% of < or =1 microg ml(-1) and we conclude that it may be useful in the treatment of non-albicans bloodstream infections.

A one-year survey of candidemia in Belgium in 2002.

A total of 211 episodes of bloodstream yeast infections in 207 patients, hospitalized in 28 Belgian hospitals participating in a National Surveillance Program, were evaluated. A total of 81% of the patients were more than 50 years of age. Candida albicans was the cause of infections in 55% of patients, 22% were due to C. glabrata and 13% to C. parapsilosis. The most common predisposing factors were antibacterial therapy (42%), residence in an intensive care unit (32.9%) and presence of an intravascular catheter (29.7%). Most patients had more than one predisposing factor. Fluconazole alone or in association with another antifungal agent was the treatment of choice for 89.7% of the cases. In vitro susceptibility testing of the isolates revealed that 99% were susceptible to amphotericin B, 95% to 5-fluorocytosine, 82% to fluconazole and 69% to itraconazole. Resistance to azoles was more common among C. glabrata isolates in the elderly. We conclude that the frequency of C. albicans infection is decreasing in Belgium and this is associated with the emergence of other species, most notably, C. glabrata.

Analysis of the antiepileptic phenyltriazine compound lamotrigine using gas chromatography with nitrogen phosphorus detection.

A method is described for the determination of lamotrigine in serum or plasma, based on gas chromatography with nitrogen-phosphorus detection. The method requires minimal sample preparation. The drug is extracted from 1.0 ml of serum at pH 11 into butylacetate containing prazepam as internal standard. An aliquot of the organic phase is then injected onto an HP-5 fused silica capillary column and analyzed with temperature programming from 90 degrees to 250 degrees C. Lamotrigine is characterized by a relative retention time of 0.832 (+/-0.03) compared with prazepam. The method is competitive with the reported high-performance liquid chromatography procedures in terms of precision and sensitivity. Coefficients of variation, calculated from the results of between-run reproducibility tests, were 6.7%, 4.6%, 4.8%, and 6.2% for samples spiked with 0.20, 1.21, 2.42 and 10.84 micrograms/ml lamotrigine, respectively. The lower limit of quantitation of the method is 0.15 microgram/ml. The proposed procedure can be integrated easily in a comprehensive toxicology screening.