JAC Advance Access originally published online on September 8, 2008
Journal of Antimicrobial Chemotherapy 2008 62(6):1379-1385; doi:10.1093/jac/dkn381
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original research |
Fungaemia caused by Candida glabrata with reduced susceptibility to fluconazole due to altered gene expression: risk factors, antifungal treatment and outcome
1 Institute of Infectious Diseases, Università Cattolica del Sacro Cuore, Rome, Italy 2 Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy
Received 6 May 2008; returned 15 June 2008; revised 7 August 2008; accepted 11 August 2008
* Corresponding author. E-mail: bposteraro{at}yahoo.it
Background: The role of Candida glabrata in fungaemia is attributed in part to its reduced susceptibility to azoles, usually due to altered expression of genes encoding drug efflux pumps. The aims of this study were to identify risk factors for fungaemia due to C. glabrata isolates with decreased susceptibility to fluconazole and to analyse the response to antifungal treatment and the clinical outcome of C. glabrata infections in hospitalized patients.
Methods: A retrospective case–case–control study was conducted at a university hospital from 2000 to 2006. Three patient groups were studied: 14 patients infected by a fluconazole-less-susceptible isolate [susceptible-dose-dependent (SDD) or resistant]; 21 patients infected by a fluconazole-susceptible (FS) isolate; and 70 uninfected controls. We measured expression of the drug efflux pump-encoding CgCDR1 and CgCDR2 genes in isolates of the two infected groups using quantitative real-time PCR.
Results: Multivariable analysis found that patients with prior fluconazole use [odds ratio (OR) 12.24, 95% confidence intervals (CIs) 1.77–84.39, P = 0.01], diabetes (OR 10.47, 95% CI 1.96–55.96, P = 0.006) and a central venous catheter (CVC) (OR 8.48, 95% CI 1.82–39.36, P = 0.006) were more likely to develop fungaemia due to a less-susceptible isolate. Previous surgery (OR 7.73, 95% CI 2.18–27.41, P = 0.002) was an independent risk factor for fungaemia due to a susceptible isolate, in addition to the presence of a CVC (OR 5.48, 95% CI 1.69–17.72, P = 0.004). The crude 30 day mortality rate was high for both case groups. Seven patients received inadequate antifungal treatment, including five infected by a fluconazole-resistant isolate but empirically treated with fluconazole; six of these seven patients died. Expression of the CgCDR genes was up-regulated in all fluconazole-resistant and, to a lesser extent, SDD isolates, but not in the FS isolates.
Conclusions: Our data suggest that when candidaemia is suspected or detected, a more broad-spectrum antifungal drug (i.e. echinocandins or amphotericin B) should be considered as initial treatment for patients with prior azole exposure.
Keywords: candidaemia , antifungal resistance , mortality , inadequate therapy , drug efflux pumps
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Tumbarello, B. Posteraro, E. M. Trecarichi, and M. Sanguinetti Fluconazole Use as an Important Risk Factor in the Emergence of Fluconazole-Resistant Candida glabrata Fungemia Arch Intern Med, August 10, 2009; 169(15): 1444 - 1445. [Full Text] [PDF]
|
|
|
|
|
|
I. Lee, N. O. Fishman, T. E. Zaoutis, K. H. Morales, M. G. Weiner, M. Synnestvedt, I. Nachamkin, and E. Lautenbach Fluconazole Use as an Important Risk Factor in the Emergence of Fluconazole-Resistant Candida glabrata Fungemia--Reply Arch Intern Med, August 10, 2009; 169(15): 1445 - 1445. [Full Text] [PDF]
|
|