Biomaterials 27 (2006) 2755–2760 In vitro effects of Ag + on planktonic and adhered cells of fluconazole-resistant and susceptible strains of Candida albicans, C. glabrata and C. krusei Shangtong Zhang à , Donald G. Ahearn, Carolina Mateus 1 , Sidney A. Crow Jr. Biology Department, Georgia State University, Kell Hall, 24 Peachtree Center Avenue, Atlanta, GA 30303, USA Received 12 October 2005; accepted 14 December 2005 Abstract Planktonic and attached cells of strains of Candida albicans, C. glabrata and C. krusei with varied susceptibilities to fluconazole (FCZ) were compared for their relative susceptibilities to Ag + via cell recovery and flow cytometric analyses. All strains lost membrane permeability and were non-recoverable upon culture after 1 h exposure in morpholino-ethanesulfonic acid (MES) buffer fortified with p2.0 mg/ml Ag + . Cells attached to silicone over a 2-h period demonstrated enhanced tolerance to FCZ and to a lesser degree to Ag + . Minimal inhibitory concentrations of Ag + in defined media increased in the order C. glabrata, C. krusei, C. albicans. Susceptibilities to Ag + did not correlate with tolerance or resistance to FCZ. r 2005 Elsevier Ltd. All rights reserved. Keywords: Candida albicans; C. glabrata; C. krusei; Fluconazole tolerance; Silver 1. Introduction Candida spp. have been reported to be the fourth ranking cause of blood stream infections in US hospitals [1]. Most infections are caused by Candida albicans, an obligate commensal and adventitious pathogen of the oral–gastro–intestinal track of man and other warm- blooded animals. This species may be found at relatively high densities at an incidence of 40–60% in the lower digestive track of asymptomatic individuals associated with a hospital environment [2]. In compromised hosts, parti- cularly in neutropenic patients, candidemia is associated with a grave invasive disease (near 40% crude mortality rate) that may involve multiple organs [1]. General iatrogenic progress, particularly increased use of indwelling devices with seriously debilitated patients, and fluconazole (FCZ) prophylaxis appear to underlie in- creased incidence of candidemia by non-C. albicans species [3–5]. FCZ prophylaxis although correlated with reduced mortality for C. albicans has been related to an increased number of infections by C. glabrata and C. krusei, species with intrinsic resistance to FCZ and lesser virulence relative to C. albicans [3,4,6,7]. Pfaller and colleagues in extensive studies of the antifungal susceptibilities of C. glabrata have found about 8% of 1432 isolates [8] and of 601 isolates [9] resistant to FCZ (MICX64 mg/ml). In the latter study, the potential for cross-resistance among the triazoles was noted, but essentially all isolates were susceptible to flucytosine and caspofungin (MICX1 mg/ml). In in vitro tests most isolates of C. albicans are susceptible to X1.0 mg/ml of FCZ, an achievable blood level, but blood levels may not correlate with clinical outcome because of the grave condition of the patient [10]. FCZ resistance may develop in most clinically important Candida spp. and FCZ tolerance may be increased when cells are attached to biomaterials [11,12]. Successful treatment of device-associated candidemia may require removal of the device. One possible strategy to circumvent such an event is the development of surfaces incompatible with Candida attachment or survival. Silver impregnated materials have a medical history of successful and sometimes controversial antimicrobial applications ARTICLE IN PRESS www.elsevier.com/locate/biomaterials 0142-9612/$ - see front matter r 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2005.12.010 à Corresponding author. Tel.: +1 404 651 3110; fax: +1 404 651 2509. E-mail address: zhangshangtong@yahoo.com (S. Zhang). 1 Current address: Milliken Chemical, Spartanburg, SC 29304, USA.