Risk Factors for Fluconazole-Resistant Candida glabrata Bloodstream Infections

MSCE, Division of Infectious Diseases, Department of Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Archives of internal medicine (Impact Factor: 17.33). 03/2009; 169(4):379-83. DOI: 10.1001/archinte.169.4.379
Source: PubMed


Bloodstream infections (BSIs) caused by Candida glabrata have increased substantially. Candida glabrata is often associated with resistance to fluconazole therapy. However, to our knowledge, risk factors for fluconazole-resistant C glabrata BSIs have not been studied.
A case-case-control study was conducted at 3 hospitals from January 1, 2003, to May 31, 2007. The 2 case groups included patients with fluconazole-resistant C glabrata BSIs (minimum inhibitory concentration > or =16 microg/mL) and patients with fluconazole-susceptible C glabrata BSIs (minimum inhibitory concentration < or =8 microg/mL). Hospitalized patients without C glabrata BSIs were randomly selected for inclusion in the control group and were frequency matched to cases on the basis of time at risk. Two case-control studies were performed using this shared control group. The primary risk factor of interest, previous fluconazole use, was evaluated at multivariate analyses, adjusting for demographic data, comorbid conditions, and antimicrobial exposures.
We included 76 patients with fluconazole-resistant C glabrata BSIs, 68 patients with fluconazole-susceptible C glabrata BSIs, and 512 control patients. Previous fluconazole use (adjusted odds ratio [95% confidence interval], 2.3 [1.3-4.2]) and linezolid use (4.6 [2.2-9.3]) were independent risk factors for fluconazole-resistant C glabrata BSIs; previous cefepime use (2.2 [1.2-3.9]) and metronidazole use (2.0 [1.1-3.5]) were independent risk factors for fluconazole-susceptible C glabrata BSIs.
Previous fluconazole use is a significant risk factor for health care-associated fluconazole-resistant C glabrata BSIs. Future studies will be needed to evaluate the effect of decreasing fluconazole use on rates of fluconazole-resistant C glabrata BSIs.

  • Source
    • "In addition, C. glabrata, C. parapsilosis, and C. krusei exhibit intrinsic resistance to most azole-based antifungal drugs (Lee et al., 2009a; Kothavade et al., 2010; Pfaller et al., 2011) and the emergence of acquired drug resistance to most commercial antifungals has been reported.(Sanglard and Odds, 2002; Pfaller et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using Candida albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC(1280TM)) using an antifungal susceptibility test (AST). To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF) cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and nine compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration. Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal candidiasis.
    Full-text · Article · Dec 2015 · Frontiers in Microbiology
  • Source
    • "The corresponding esters 3b/3c did not show significant antimicrobial activities. The MIC (minimum inhibitory concentration) against the opportunistic pathogen Candida glabrata, which is often associated with resistance to fluconazole therapy [16] [17], was determined to be 25 µg/mL (2c), 10 µg/mL (2d), and 5 µg/mL (2e) (clotrimazole: 2.5 µg/mL) [11]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A novel series of imidazol-5-yl carbinols and their 4-chlorobenzoyl esters has been synthesized by the Grignard reaction and subsequent esterification. These compounds were screened for their antimicrobial activities in an agar diffusion assay. The compounds with C10 to C12-alkyl side chains displayed significant antimycotic activity.
    Full-text · Article · Sep 2013 · Scientia Pharmaceutica
  • Source
    • "This statement is confounded by reports from outside the United States, including France (Richet et al., 2002), Italy (Luzzati et al., 2000; Tortorano et al., 2002), Switzerland (Marchetti et al., 2004), Finland (Poikonen et al., 2003), Iceland (Asmundsdottir et al., 2002), Taiwan (Chen et al., 2003; Cheng et al., 2004; Hseuh et al., 2002, 2005), and Norway (Sandven et al., 2006) that indicate that C. glabrata has not increased as a cause of IC to the extent seen in the United States despite an increase in the use of fluconazole in each of those countries. It is now apparent that the dramatic variation in the frequency of C. glabrata as a cause of IC and its associated resistance profile may be influenced not only by exposure to azoles, but also by patient age, underlying disease, and geographic location (Alexander et al., 2005; Arendrup et al., 2008; Chow et al., 2008; Hachem et al., 2008; Klevay et al., 2009; Laupland et al., 2005; Lee et al., 2009; Magill et al., 2006; Malani et al., 2005; Pasqualotto et al., 2008; Pfaller et al., 2003, 2009b; Riddell and Kauffman, 2008). The results of the present study demonstrate the dynamic nature of both the prevalence of C. glabrata as a cause of IC and its susceptibility to the azoles. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Geographic differences in frequency and azole resistance among Candida glabrata may impact empiric antifungal therapy choice. We examined geographic variation in isolation and azole susceptibility of C. glabrata. We examined 23 305 clinical isolates of C. glabrata during ARTEMIS DISK global surveillance. Susceptibility testing to fluconazole and voriconazole was assessed by disk diffusion, and the results were grouped by geographic location: North America (NA) (2470 isolates), Latin America (LA) (2039), Europe (EU) (12 439), Africa and the Middle East (AME) (728), and Asia-Pacific (AP) (5629). Overall, C. glabrata accounted for 11.6% of 201 653 isolates of Candida and varied as a proportion of all Candida isolated from 7.4% in LA to 21.1% in NA. Decreased susceptibility (S) to fluconazole was observed in all geographic regions and ranged from 62.8% in AME to 76.7% in LA. Variation in fluconazole susceptibility was observed within each region: AP (range, 50-100% S), AME (48-86.9%), EU (44.8-88%), LA (43-92%), and NA (74.5-91.6%). Voriconazole was more active than fluconazole (range, 82.3-84.2% S) with similar regional variation. Among 22 sentinel sites participating in ARTEMIS from 2001 through 2007 (84 140 total isolates, 8163 C. glabrata), the frequency of C. glabrata isolation increased in 14 sites and the frequency of fluconazole resistance (R) increased in 11 sites over the 7-year period of study. The sites with the highest cumulative rates of fluconazole R were in Poland (22% R), the Czech Republic (27% R), Venezuela (27% R), and Greece (33% R). C. glabrata was most often isolated from blood, normally sterile body fluids and urine. There is substantial geographic and institutional variation in both frequency of isolation and azole resistance among C. glabrata. Prompt species identification and fluconazole susceptibility testing are necessary to optimize therapy for invasive candidiasis.
    Full-text · Article · Mar 2010 · Diagnostic microbiology and infectious disease
Show more

We use cookies to give you the best possible experience on ResearchGate. Read our cookies policy to learn more.