Five-year evaluation of bloodstream yeast infections in a tertiary hospital: the predominance of non-C. albicans Candida species

This is a retrospective observational study of clinical and epidemiologic data from bloodstream yeast infections over 5 years (2004-2008) in a tertiary-care hospital. During this period, there were 52 such infections, at a rate of 2.4 per 1,000 hospital admissions. Non-C. albicans Candida species and other genera were responsible for 82% of infections, with C. tropicalis and C. parapsilosis being the most common. In 2008 no C. albicans infections occurred. Several uncommon fungal pathogens were observed, including Trichosporon asahii, Rhodotorula spp. and Candida zeylanoides. Of 16 isolates tested, 3 (19%) were resistant to fluconazole, including one C. zeylanoides (MIC 8 mu g/ml) and one C. tropicalis (MIC 16 mu g/ml) isolate, as well as intrinsically resistant C. krusei. All isolates tested were susceptible to itraconazole (n = 7) and amphotericin B (n = 8). Yeast infections were associated with severe underlying diseases, mainly hematological/solid cancers (71%), hospitalization in the ICU (41%), central venous catheters (80%), and use of antimicrobials (94%). The overall mortality rate was 50%. Our finding of a predominance of non-C. albicans Candida species infection with uncommon yeasts, and fluconazole resistance, suggests the need for continuous surveillance of fungemia and of antibiotic susceptibility trends, in order to adopt treatment strategies applicable to particular healthcare institutions.

In vitro synergism of simvastatin and fluconazole against Candida species

Systemic fungal infections are responsible for high mortality rates. Several species of fungi may be involved, but Candida spp. is the most prevalent. Simvastatin is used to lower cholesterol and also exhibits antifungal action. The aim of this study was to evaluate the synergistic action of simvastatin with fluconazole against strains of Candida spp. Susceptibility testing was performed according to protocol M27-A3, by broth microdilution method and the synergistic effect of simvastatin and fluconazole was calculated based on FICI (Fractional Inhibitory Concentration Index). Eleven strains were evaluated, and simvastatin showed a synergistic effect with fluconazole against 10 (91%) of the Candida spp. strains tested. Simvastatin may be a valuable drug in the treatment of systemic infections caused by Candida spp.

FREQUENCY OF Candida SPECIES IN A TERTIARY CARE HOSPITAL IN TRIANGULO MINEIRO, MINAS GERAIS STATE, BRAZIL

Infections by Candida species are a high-impact problem in public health due to their wide incidence in hospitalized patients. The goal of this study was to evaluate frequency, susceptibility to antifungals, and genetic polymorphism of Candida species isolated from clinical specimens of hospitalized patients. The Candida isolates included in this study were obtained from blood cultures, abdominal fluids, and central venous catheters (CVC) of hospitalized patients at the Clinical Hospital of the Federal University of Uberlândia during the period of July 2010 - June 2011. Susceptibility tests were conducted by the broth microdilution method. The RAPD-PCR tests used employed initiator oligonucleotides OPA09, OPB11, and OPE06. Of the 63 Candida isolates, 18 (28.5%) were C. albicans, 20 (31.7%) were C. parapsilosis complex species, 14 (22.2%) C. tropicalis, four (6.4%) C. glabrata, four (6.4%) C. krusei, two (3.3%) C. kefyr, and one (1.6%) C. lusitaniae. In vitro resistance to amphotericin B was observed in 12.7% of isolates. In vitroresistance to azoles was not detected, except for C. krusei. The two primers, OPA09 and OPB11, were able to distinguish different species. Isolates of C. albicans and C. parapsilosis complex species presented six and five clusters, respectively, with the OPA09 marker by RAPD-PCR, showing the genetic variability of the isolates of those species. It was concluded that members of the C. parapsilosis complex were the most frequent species found, and most isolates were susceptible to the antifungals amphotericin B, flucozanole, and itraconazole. High genetic polymorphisms were observed for isolates of C. albicans and C. parapsilosis complex species, mainly with the OPA09 marker.

Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species

The azoles are the class of medications most commonly used to fight infections caused by Candida sp. Typically, resistance can be attributed to mutations in ERG11 gene (CYP51) which encodes the cytochrome P450 14α-demethylase, the primary target for the activity of azoles. The objective of this study was to identify mutations in the coding region of theERG11 gene in clinical isolates of Candidaspecies known to be resistant to azoles. We identified three new synonymous mutations in the ERG11 gene in the isolates of Candida glabrata (C108G, C423T and A1581G) and two new nonsynonymous mutations in the isolates of Candida krusei - A497C (Y166S) and G1570A (G524R). The functional consequence of these nonsynonymous mutations was predicted using evolutionary conservation scores. The G524R mutation did not have effect on 14α-demethylase functionality, while the Y166S mutation was found to affect the enzyme. This observation suggests a possible link between the mutation and dose-dependent sensitivity to voriconazole in the clinical isolate of C. krusei. Although the presence of the Y166S in phenotype of reduced azole sensitivity observed in isolate C. kruseidemands investigation, it might contribute to the search of new therapeutic agents against resistant Candida isolates.

Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study.

OBJECTIVES: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. DESIGN: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. SETTING: EPIC II included 1265 intensive care units in 76 countries. PATIENTS: Patients in participating intensive care units on study day. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. CONCLUSION: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use.

Evaluation of the susceptibility of pathogenic Candida species to fluconazole. Fluconazole Global Susceptibility Study Group.

A fluconazole 25 microg disk diffusion test was used to test 2230 consecutively isolated Candida strains from 42 different hospital laboratories in 23 countries. Ninety seven percent of 1634 Candida albicans isolates and 83.4% of 596 non-Candida albicans isolates were susceptible to fluconazole, applying the proposed breakpoints (> or = 26 mm for susceptible strains and 18-25 mm for dose-dependent susceptible strains). This is the first hospital laboratory study to evaluate a large number and wide range of sequential Candida isolates from patients with all types of hospital infections. The fluconazole disk diffusion test appears to be a low-cost, reproducible, and accurate means of assessing the in vitro susceptibility of Candida isolates.

Antifungal activity of tri- and tetra-thioureido amino derivatives against different Candida species

The in vitro antifungal activity of six thioureido substituted amines (P1-P6) was evaluated against Candida species, including Candida albicans, C. glabrata, C. krusei and C. parapsilosis. These tri- and tetra-thioureido amino derivatives with different methylation levels were synthesised through easy synthetic routes to evaluate their antifungal properties against Candida species. Among all studied derivatives, the tri-(2-thioureido-ethyl)-amine (P1) was the most active compound inhibiting C. albicans and C. glabrata at a concentration of 0.49 mu g ml(-1); P3, the N,N `,N ``,N ```-hexamethyl-derivative, also showed inhibitory activity against C. albicans and C. glabrata, but in higher concentrations (250 mu g ml(-1)). The N,N `,N ``,N ```-tetramethylated amine (P5) only inhibited the growth of C. glabrata, but its corresponding N,N `,N ``,N ```-octamethyl derivative (P6) was also active against C. glabrata (125 mu g ml(-1)) and it was the only compound active against C. parapsilosis. P2 and P4 showed no significant antifungal activity. The structure-activity relationship of the thioureido-substituted derivatives indicates that the molecular branching and the alkylation levels can influence the antifungal activity. This study demonstrated that thioureido derivatives exhibited significant antifungal activity against Candida species and that they can be considered as a very promising bioactive lead compound to develop novel antifungal agents.

Species distribution and susceptibility profile of Candida species in a Brazilian public tertiary hospital

Background. Species identification and antifungal susceptibility tests were carried out on 212 Candida isolates obtained from bloodstream infections, urinary tract infections and dialysis-associated peritonitis, from cases attended at a Brazilian public tertiary hospital from January 1998 to January 2005. Findings. Candida albicans represented 33% of the isolates, Candida parapsilosis 31.1%, Candida tropicalis 17.9%,Candida glabrata 11.8%, and others species 6.2%. In blood culture, C. parapsilosis was the most frequently encountered species (48%). The resistance levels to the antifungal azoles were relatively low for the several species, except for C. tropicalis and C. glabrata. Amphotericin B resistance was observed in 1 isolate of C. parapsilosis. Conclusions. The species distribution and antifungal susceptibility herein observed presented several epidemiological features common to other tertiary hospitals in Latin American countries. It also exhibited some peculiarity, such as a very high frequency of C. parapsilosis both in bloodstream infections and dialysis-associated peritonitis. C. albicans also occurred in an important number of case infections, in all evaluated clinical sources. C. glabrata presented a high proportion of resistant isolates. The data emphasize the necessity to carry out the correct species identification accompanied by the susceptibility tests in all tertiary hospitals. © 2010 Bagagli et al; licensee BioMed Central Ltd.

Candida species: Current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options

The incidence of fungal infections has increased significantly, so contributing to morbidity and mortality. This is caused by an increase in antimicrobial resistance and the restricted number of antifungal drugs, which retain many side effects. Candida species are major human fungal pathogens that cause both mucosal and deep tissue infections. Recent evidence suggests that the majority of infections produced by this pathogen are associated with biofilm growth. Biofilms are biological communities with a high degree of organization, in which micro-organisms form structured, coordinated and functional communities. These biological communities are embedded in a self-created extracellular matrix. Biofilm production is also associated with a high level of antimicrobial resistance of the associated organisms. The ability of Candida species to form drugresistant biofilms is an important factor in their contribution to human disease. The study of plants as an alternative to other forms of drug discovery has attracted great attention because, according to the World Health Organization, these would be the best sources for obtaining a wide variety of drugs and could benefit a large population. Furthermore, silver nanoparticles, antibodies and photodynamic inactivation have also been used with good results. This article presents a brief review of the literature regarding the epidemiology of Candida species, as well as their pathogenicity and ability to form biofilms, the antifungal activity of natural products and other therapeutic options. © 2013 SGM.

Identification of Candida species in the clinical laboratory: A review of conventional, commercial, and molecular techniques

In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so-called non-albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time-consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species. © 2013 John Wiley & Sons A/S.

Susceptibility profile of a Brazilian yeast stock collection of Candida species isolated from subjects with Candida-associated denture stomatitis with or without diabetes

Objective: This study investigated the susceptibility of 198 clinical isolates of Candida species against caspofungin, amphotericin B, itraconazole, and fluconazole. Study Design: Suspensions of the microorganisms were spread on Roswell Park Memorial Institute (RPMI) agar plates. Etest strips were placed on the plates, and the minimal inhibitory concentration (MIC) was read after incubation (48 h at 37°C). Data were analyzed by a factorial analysis of variance and a 2 × 2 post hoc test (α = .05). Results: C glabrata showed the highest MIC values (P < .001) against caspofungin, itraconazole, and fluconazole. For amphotericin B, the MIC values of C tropicalis and C glabrata (P = .0521) were higher than those of C albicans (P < .001). Itraconazole was the least effective antifungal; 93.3% of the C glabrata isolates, 3.3% of the C albicans, and 1.3% of the C tropicalis were resistant. All microorganisms were susceptible to caspofungin and amphotericin B. Conclusions: Caspofungin and amphotericin B should be recommended as an effective alternative for the management of oral Candida infections when treatment with topical or other systemic drugs has definitely failed. © 2013 Elsevier Inc. All rights reserved.

Candida species biofilm and Candida albicans ALS3 polymorphisms in clinical isolates

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A mini review of Candida species in hospital infection: epidemiology, virulence factor and drugs resistance and prophylaxis

The introduction of more efficient diagnostic methods, new techniques in surgery and transplantation, antibiotics and chemotherapeutics more potent and novel materials for prostheses, catheters and probes significantly increased the life expectancy and quality of life of critically ill patients, on the other hand, hospital-acquired infections emerged as important iatrogenic complications. Invasive infections are a growing problem in public health hospitals in Brazil and worldwide. Among the various etiological agents found in the hospital environment, the genus Candida has been the third most frequently isolated pathogen. In general, invasive fungal infections are associated with high morbidity and mortality, difficulties in diagnosis, antimicrobial resistance, length of hospital stay and increased hospital costs. This mini review of the literature describes about epidemiology of hospital infection of Candida species, as well as its virulence factors and drugs resistance

Contribution of plant-derived phenolic compounds to combat Candida species biofilms

Opportunistic fungal infections, namely involving Candida species, constitute a hot topic for scientific researchers. The present wor1( aims to access antifungal potential of plant-derived phenolic extrac:ls against planktonic cells and biofilms of Candida species. Eucalyptvs globulus Labill. (blue gum), Glycyrrhiza glabra L. (licorice), Juglans regia L. (walnut) and Salvia officina/is L. (sage) evidenced to be the most effective Candida growth inhibitors, using disc diffusion assay. Minmal inhibitory (MIC) and minimal fungicidal (MFC) concentrations, and chemical composition of extracts by using HPLC-DAO-ESVMS were also determined. Blue gum and walnut mainly exerted fungistatic potential, while sage exerted an interesting anti-Candida potential. However, the most prominent candidacidal potential was observed to licorice extract, being achieved the lowest MIC and MFC values. The candidacidal potential of these phenolic extracts was mainly attributed to their high abundance in flavonoids, mainly flavones: luteolin (sage) and apigen~ derivatives (licorice), and flavanones: liQuiritin derivatives (licorice). In order to deepen the knowledge on the most effective extract. its abiity to inhibit biofilm formation was evaluated. Overall, a double concentration of MFC value was necessary to achieve similar results in biofims. Row cytometry assays were also carried out, and the obtained results revealed that primary lesion of cellular membrane appear to be most relevant mode of action. Thus, plant derived phenolic compounds evidence a promising potential to combat Candida species biofilms, both individually or combined with conventional therapy.

Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species

The azoles are the class of medications most commonly used to fight infections caused by Candida sp. Typically, resistance can be attributed to mutations in ERG11 gene (CYP51) which encodes the cytochrome P450 14α-demethylase, the primary target for the activity of azoles. The objective of this study was to identify mutations in the coding region of the ERG11 gene in clinical isolates of Candida known to be resistant to azoles. We identified three new synonymous mutations in the ERG11 gene in the isolates of Candida glabrata (C108G, C423T and A1581G) and two new nonsynonymous mutations in the isolates of Candida krusei - A497C (Y166S) and G1570A (G524R). The functional consequence of these nonsynonymous mutations was predicted using evolutionary conservation scores. The G524R mutation did not have effect on 14α-demethylase functionality, while the Y166S mutation was found to affect the enzyme. This observation suggests a possible link between the mutation and dose-dependent sensitivity to voriconazole in the clinical isolate of C. krusei. Although the presence of the Y166S in phenotype of reduced azole sensitivity observed in isolate C. krusei demands investigation, it might contribute to the search of new therapeutic agents against resistant Candida isolates.