Fluconazole-resistant Candida Spp Research Articles

Mangiferin potentiates the activity of antifungal agents against fluconazole-resistant Candida spp.

Aim: To evaluate the antifungal activity of mangiferin against Candida spp. resistant to fluconazole.Materials & methods: The antifungal activity of mangiferin was assessed using broth microdilution and its interaction with azoles and amphotericin B was evaluated by checkerboard. The activity of mangiferin against Candida spp. biofilms was assessed using the MTT colorimetric assay and its possible mechanism of action was evaluated using flow cytometry.Results: Mangiferin showed activity against Candida albicans, Candida tropicalis and Candida parapsilosis resistant to fluconazole and showed synergism with azoles and amphotericin B. Mangiferin increased the activity of antifungals against Candida biofilms and caused depolarization of the mitochondrial membrane and externalization of phosphatidylserine, suggesting apoptosis.Conclusion: mangiferin combined with antifungals has potential against Candida spp.

Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp.

In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.

Antifungal Activity, Gas Chromatographic-Mass Spectrometric Analysis And in silico Study of Punica Granatum Peel Extracts Against Fluconazole Resistant Strains of Candida Species

Candida species is the common cause of opportunistic fungal infections all over the world with increased mortality and morbidity especially in immunosuppressed patients. Fluconazole is the first line therapy for candidiasis. The antifungal resistance pattern in high-risk patients is a major concern. The present study was aimed to assess the anticandidal activity of Punica granatum peel against fluconazole resistant Candida species isolated from HIV patients. Ethanol, chloroform, petroleum ether and aqueous extracts of the peel of P. granatum were evaluated against standard strains of Candida spp. and fluconazole resistant clinical isolates by agar diffusion and broth dilution techniques. The GC-MS analysis of the extracts was performed to identify the phytochemicals present in it. The predominant phytochemical was subjected to molecular docking study to determine its binding efficacy with lanosterol 14-alpha demethylase. P. granatum peel extracts showed excellent anticandidal activity with ethanol extract exhibiting the most inhibitory activity. C. albicans and C. krusei were the most inhibited and C. parapsilosis was the least inhibited species. The GC-MS analysis of the ethanol extract identified five predominant phytochemicals. On docking studies, the five phytochemicals showed a good binding to the lanosterol 14-alpha demethylase. The present study is the first report on the antifungal activity of various extracts of P. granatum against fluconazole resistant Candida isolates. Ethanol extract of P. granatum peel showed excellent anticandidal activity against fluconazole resistant Candida spp. Hence, it can be explored further to identify a potential drug candidate.

Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant Candida spp.

Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant Candida spp. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant C. albicans, C. tropicalis and C. krusei in vitro. Most of these compounds showed good synergistic activities against C. tropicalis. Among them, compound 9 exhibited significant synergistic activities against Candida spp. SARs were also discussed. In particular, a cell growth test exhibited that a combination of 1 μg ml-1 fluconazole and 64 μg ml-1 or 128 μg ml-1 compound 9 showed the most potent fungicidal effect against C. tropicalis. The synergistic effect may be associated with the changes of the intracellular ATP content and cell membrane permeability. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for fluconazole-resistant candidiasis.

Green synthesis and antifungal activity of Al2O3NPs against fluconazole-resistant Candida spp isolated from a tertiary care hospital

Antifungal activity of ecofriendly and cost effectively prepared Al2O3NPs onCandia alibicans.

Association of clinical and demographic factors in invasive candidiasis caused by fluconazole-resistant Candida species: a study in 15 hospitals, Medellín, Colombia 2010–2011

Candida is the most important agent of fungal infections. Several risk factors have been described associated with invasive infection by fluconazole-resistant Candida spp. A prospective cross-sectional study with case–control analysis was conducted. Case group patients with fluconazole-resistant Candida isolate were included; control group were patients with fluconazole-susceptible Candida spp. A multivariate logistic regression model was performed. Three hundred isolates of Candida spp. were analyzed. Most frequent species were Candida albicans/Candida dubliniensis (48.3%) and Candida tropicalis (22.3%). Posaconazole susceptibility was 93.7%; voriconazole, 84%; and fluconazole, 78.7%. Susceptibility to anidulafungin and caspofungin was 92.7% and 92.3%, respectively. Neutropenia (adjusted odds ratio [aOR] 6.5, 95% confidence interval [CI] 1.0–43.1), antifungal exposure (aOR 5.1, 95% CI 2.3–11.2), and antituberculosis therapy (aOR 7.7, 95% CI 1.4–43.2) were associated to fluconazole resistance. Susceptibility results are useful to guide the selection of empiric antifungal treatment and the design of local therapeutic guidelines. Previous antifungal exposure suggests possible resistance to fluconazole, pointing towards the selection of a different class of antifungal agents.

Routine Use of Fluconazole Prophylaxis in a Neonatal Intensive Care Unit Does Not Select Natively Fluconazole-Resistant Candida Subspecies

We have previously demonstrated efficacy against fungal colonization and infection of fluconazole prophylaxis that was routinely administered since 2001 in our ICU for preterm infants <1500 g at birth (VLBW). With prolonged use, concerns exist for the emergence of acquired fungal resistance and of Candida subspecies that are natively fluconazole-resistant (NFR), mostly Candida glabrata and Candida krusei. We evaluated retrospectively all clinical and surveillance fungal isolates obtained from VLBW infants in our NICU during a 10-year period (1997-2006). Each fungal isolate was speciated, infants colonized or infected with NFR-Candida spp were identified and the incidence rates of colonization and infection by these fungal species were calculated. A comparison was made of the 6-year (2001-2006) prophylaxis period with the 4-year (1997-2000) preprophylaxis period. Overall, colonization by NFR-Candida spp ranged between 2.8% and 6.6% of VLBW infants yearly admitted, without any increasing trend during the study period. There were 18 of 434 (4.1%) neonates colonized by these species. Five episodes of systemic fungal infections caused by NFR-Candida spp occurred (incidence rate, 1.1%). No significant differences were detected when compared with the preprophylaxis period, when 11 of 295 infants (3.7%) were colonized by NFR-Candida spp and 4 episodes of infection occurred (1.4%) (P = 0.84 and 0.76, respectively). Fluconazole prophylaxis administered to VLBW neonates in 4- to 6-week courses after birth does not lead to the emergence of natively fluconazole-resistant Candida spp.

Candidemia in nonneutropenic critically ill patients: Risk factors for non-albicans Candida spp.

The objective of this study was to determine the clinical features associated with candidemia caused by non-albicans Candida spp. and with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei) among candidemic intensive care unit patients. The authors conducted a nationwide prospective cohort study. The study was conducted in Australian intensive care units. All patients with intensive care unit-acquired candidemia over a 3-yr period were included in the study. Clinical risk factors occurring up to 30 days before candidemia, Candida spp. associated with candidemia, and outcomes were determined. Risk factors associated with either non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata or C. krusei) were assessed using multivariate logistic regression. Among 179 episodes of intensive care unit-acquired candidemia, C. albicans accounted for 62%, C. glabrata 18%, C. krusei 4%, and other Candida spp. 16%. Independently significant variables associated with non-albicans Candida bloodstream infection included recent prior gastrointestinal surgery (adjusted odds ratio, 2.87; 95% confidence interval, 1.68-4.91) and recent prior systemic antifungal exposure (4.6; 1.36-15.53). Those associated with potentially fluconazole-resistant candidemia included recent prior gastrointestinal surgery (3.31; 1.79-6.11) and recent prior fluconazole exposure (5.47; 1.23-24.32). No significant differences in outcomes were demonstrated for non-albicans or potentially fluconazole-resistant candidemia. Among candidemic intensive care unit patients, prior gastrointestinal surgery and systemic antifungal exposure were significantly associated with both a non-albicans Candida spp. and a potentially fluconazole-resistant Candida spp.

The Impact of Primary Prophylaxis for Cryptococcosis on Fluconazole Resistance in Candida Species

To the Editor: Primary anticryptococcal prophylaxis in advanced HIV infection is generally not recommended, given no evidence for improved survival, associated excess costs, and the potential risk for emerging drug resistance.1 In Thailand, however, the prevalence of cryptococcosis is high, primary fluconazole prophylaxis has been associated with reduced invasive fungal infections and mortality, and primary cryptococcal prophylaxis is recommended in national HIV treatment guidelines.2,3 Although primary prophylaxis has not been shown to select for fluconazole resistance among patients who subsequently developed cryptococcal meningitis,4 the impact of primary anticryptococcal prophylaxis on the emergence of fluconazole resistance in Candida species among patients with HIV infection has not been evaluated. Thammasart University is a 450-bed tertiary care referral hospital in central Thailand. Infectious diseases consultative services and care formally began in January 2003, with an annual increase in the number of HIV-related admissions from the year 2002 (N = 125) to the year 2006 (N = 405). Most HIV-related admissions were for the evaluation of fever; 45% of cases had CD4 counts <100 cells/μL.5 Since 2003, primary anticryptococcal prophylaxis has been routinely prescribed to patients with advanced HIV infection (CD4 counts <100 cells/μL), as recommended by the Thai National HIV Treatment Guideline.3 We conducted a drug utilization and antimicrobial resistance correlation analysis of inpatient antifungal consumption and the prevalence of fluconazole-resistant Candida spp. among hospitalized adults with HIV infection for the calendar years 2002 to 2006. The rate of inpatients' antifungal use was recorded as the total number of grams of drug, converted into defined daily doses (DDDs) per 1000 patient-days, in accordance with the recommendations of the World Health Organization.6 Oral and parenteral drug expenditures were included for analysis. Antimicrobial susceptibility patterns of Candida spp., and the proportion of resistant isolates, were derived from existing data in the Microbiology Department. Correlations between antifungal consumption and resistance were assessed by Pearson correlation analyses. There was an incremental increase in oral fluconazole consumption (from 6 to 35 DDDs per 1000 patient-days) during the years 2002 to 2006, whereas the consumption of oral itraconazole and other parenteral antifungal agents (eg, fluconazole, amphotericin B) remained unchanged (Table 1). Notably, 86% of oral fluconazole prescriptions were for primary anticryptococcal prophylaxis, and 36% of the patients prescribed oral fluconazole had CD4 counts >100 cells/μL for at least 6 months. During the same 5-year period that the prevalence of fluconazole-resistant Candida spp. increased from 2% to 33%, detection of Candida albicans significantly declined from 95% to 54% (see Table 1). A significant correlation between oral fluconazole consumption and fluconazole-resistant Candida spp. (r = 0.71, P < 0.001) was noted. No correlation was evident for fluconazole-resistant Candida spp. and other antifungal drugs.TABLE 1: Antifungal Consumptions and Incidence of Inpatient Candida spp. From Year 2002 Through 2006Our study findings have significant implications for clinical and laboratory practices. The incremental increase in oral fluconazole consumption was temporally attributed to the national HIV prevention policy for opportunistic infections. Notably, this increase in fluconazole use correlated with increased fluconazole-resistant Candida spp. Our findings suggest that systematic surveillance for fluconazole-resistant Candida spp. is judicious in countries where primary anticryptococcal prophylaxis is given to persons with advanced HIV infection. In addition, our findings imply potential benefit from interventions that minimize inappropriate antifungal use in developing countries. Focused educational interventions aimed at improving guideline compliance with prophylaxis against opportunistic infections are needed. Anucha Apisarnthanarak, MD* Linda M. Mundy, MD† *Division of Infectious Diseases Thammasart University Hospital Pratumthani, Thailand †Saint Louis University School of Public Health Saint Louis, MO

Fluconazole resistant oral candidiasis in HIV-infected patients.

To evaluate the risk factors associated with the emergence of fluconazole resistant Candida spp. in HIV-infected patients with oral candidiasis. Candida spp. were isolated from oral swabs and tested in vitro for resistance to fluconazole. The factors potentially correlated with vazole-resistent Candida spp. infections were investigated. Fifty-one out of 118 patients (43%) with oral candidiasis had fluconazole resistant Candida spp. The following factors were significantly associated with the development of fluconazole resistance: (1) more than five episodes of oral candidiasis in the previous year (P < 0.001); (2) fluconazole therapy in the previous 6 months (P < 0.001); (3) C3 category of HIV infection (P < 0.001); and (4) low number of TCD4+ cells (< 50 mm3, P = 0.002). According to multivariate analysis, previous therapy with fluconazole was the only risk factor that independently influenced the development of Candida spp. resistance (P = 0.003). The prophylaxis and therapy of mild fungal infections in HIV-infected patients, which may lead to azole resistance, should be carefully considered.