884. Wild-Type MIC Distributions and Epidemiological Cutoff Values for Fluconazole,  Posaconazole and Voriconazole versus Cryptococcus neoformans as Determined by 72 hour CLSI Broth Microdilution Method
Session: Poster Abstract Session: Antifungal Therapy
Saturday, October 22, 2011
Room: Poster Hall B1
Background:  When clinical susceptibility (S) breakpoints (CBPs) are absent, establishing wild-type (WT) MIC distributions and epidemiological cutoff values (ECVs) provides sensitive means for detecting emerging resistance.  We determined species-specific ECVs for fluconazole (FLC), posaconazole (PSC) and voriconazole (VRC) using a large global collection of C. neoformans (CNEO) isolates obtained from the ARTEMIS and SENTRY Antimicrobial Surveillance Programs.

Methods: From 2006-2009, 285 invasive clinical isolates of CNEO were collected from 61 centers worldwide (178 isolates from ARTEMIS and 107 from SENTRY Program) and S testing was performed against FLC,  PSC and VRC using CLSI M27-A3 broth microdilution method (72h incubation). ARTEMIS isolates were tested at the Univ. of Iowa and SENTRY Program isolates were tested at JMI Laboratories and the results were combined for analysis. An additional collection of 1010 isolates tested against FLC between 1996-2008 were used to assess temporal trends in the frequency of non-WT isolates.

Results: The modal MICs (µg/ml) for FLC, PSC and VRC, respectively, were: 4, 0.12 and 0.06.  The ECVs expressed as µg/ml (% of isolates that had MIC ≤ ECV) for FLC, PSC and VRC, respectively, were: 8 (96.9), 0.25 ( 96.5) and 0.12 ( 95.1). Temporal trends in the emergence of non-WT strains (% of isolate MICs > ECV) for the time periods 1996-2000, 2001-2004, 2005-2008, respectively, for FLC were 3.6, 3.8 and 0.5.

Conclusion:  In the absence of CBPs for FLC, PSC and VRC these WT MIC distributions and ECVs will be useful in surveillance for emergence of azole reduced S among CNEO.  Application of the FLC ECV to a large collection of CNEO tested over time (1996-2008) revealed a decrease in the frequency of non-WT strains over time. These findings are consistent with those of more limited surveys in developed countries suggesting that CNEO Sto FLC has improved since the introduction of antiretroviral therapy. Continued surveillance using these ECVs for the azoles and CNEO is warranted

Subject Category: M. Mycology including clinical and basic studies of fungal infections

Michael A. Pfaller, M.D.1, Daniel J. Diekema2, Shawn A. Messer1, Mariana Castanheira, PhD1 and Ronald Jones, MD1, (1)Microbiology, JMI Laboratories, North Liberty, IA, (2)University of Iowa Carver College of Medicine, Iowa City, IA


M. A. Pfaller, None

D. J. Diekema, Merck: Grant Investigator, Research grant

S. A. Messer, None

M. Castanheira, None

R. Jones, None

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