Article

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

ABSTRACT

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.

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    • "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). "
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    • "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]. "
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    • "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. "
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