Virulence factors and susceptibility patterns of candida species isolated from patients with obstructive uropathy and bladder cancer

ABSTRACT

Candiduria is a common and high risk event in patients with uropathies and cancer. In this study we investigated the distribution of 3 virulence factors namely biofilm formation [BF], secreted aspartyl proteinase [SAP] and phospholipase activity [PLA] among different Candida species isolated from inpatients with candiduria. The susceptibility patterns of Candida isolates to antifungal agents, including the new voriconazole, were evaluated in vitro and the association of these virulence factors with resistance was studied. Urine specimens from 250 patients divided into 3 groups were examined Group1 [n=50] cancer bladder; Group2 [n=100] obstructive uropathy and Group 3 [n=100] simple recurrent urinary tract infection [UTI]. Candida isolates were identified by CHROM-agar, and by Candifast Es Twin test. Susceptibility testing to antifungal agents was evaluated by disc diffusion test using fluconazole [FCZ] 30microg discs and E test strips for Minimum inhibitory concentration [MIC] determination of FCZ, voriconazole [VCZ] and Amphotericin B [AMB]. Assessment of BF was performed by tube and spectrophotometric plate adherence methods and quantitated by crystal violet staining and XTT reduction assays. PLA was screened using Sabouraud egg yolk agar and SAP was detected using bovine serum albumin agar [BSA]. The overall prevalence of candiduria was 24% with highest incidence among obstructive uropathy patients [67.2%]. Isolation rate of Candida [C]. nonalbicans species [C. tropicalis ,C. krusei and C. glabrata] was significantly higher than C. albicans [73.1% versus 26.8%; p256microg/ml]. Voriconazole, the new triazole antifungal agent, was active against all isolated Candida species with a sensitivity rate of 82%-100% and low MIC values [0.064-1microg/ml] except in C. glabrata species [22%]. All isolated Candida species were more sensitive to VCZ compared to FCZ; particularly C. krusei isolates [90% versus 9%]. AMB remained to be an effective drug with absolute sensitivity and low MICproduction are important virulence traits in candiduria causing UTI. BF is common in non-albicans species particularly C. krusei and C. tropicalis in patients with obstructive uropathies. There was good correlation between the virulence traits and resisance to FCZ, so it may no longer be the drug of choice for treatment of candiduria. AMB or VCZ are better alternatives. The availability of VCZ in oral preparations make us recommend its use for treatment of candiduria in case of resistance to FCZ. C. glabrata remains to be problematic and is best treated by AMB. Future studies should focus on whether in vitro detection of virulence factors can predict treatment failure in vivo