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Antimicrobial Agents and Chemotherapy, July 2006, p. 2464-2470, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.01520-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Results Obtained with Various Antifungal Susceptibility Testing Methods Do Not Predict Early Clinical Outcome in Patients with Cryptococcosis

E. Dannaoui,^1,2* M. Abdul,¹ M. Arpin,⁴ A. Michel-Nguyen,⁵ M. A. Piens,⁴ A. Favel,⁶ O. Lortholary,^1,3 F. Dromer,¹ and the French Cryptococcosis Study Group

Centre National de Référence Mycologie et Antifongiques, Unité de Mycologie Moléculaire, CNRS FRE2849, Institut Pasteur, 75724 Paris Cedex 15, France,¹ Université Paris Descartes, Faculté de Médecine, AP-HP, Hôpital Européen Georges Pompidou, Unité de Parasitologie-Mycologie, 75015 Paris, France,² Université Paris Descartes, Faculté de Médecine, AP-HP, Hôpital Necker-Enfants-Malades, Service des Maladies Infectieuses et Tropicales, 75743 Paris Cedex 15, France,³ Laboratoire de Parasitologie, Mycologie Médicale et Pathologie Exotique, Université Claude Bernard Lyon I, 69373 Lyon Cedex 08, France,⁴ Laboratoire de Microbiologie, CHU Timone, and Hôpital St. Joseph, 13000 Marseille, France,⁵ Laboratoire de Botanique, Cryptogamie et Biologie Cellulaire, Faculté de Pharmacie, 13385 Marseille Cedex 5, France⁶

Received 28 November 2005/ Returned for modification 14 February 2006/ Accepted 21 April 2006

The in vitro susceptibilities of Cryptococcus neoformans isolates from consecutive human immunodeficiency virus-positive and -negative patients to the antifungal agents fluconazole, amphotericin B, and flucytosine were determined by different techniques, including the CLSI method, Etest, and broth microdilution in yeast nitrogen base (YNB) medium, during a multicenter prospective study in France. The relationship between the in vitro data and the clinical outcome 2 weeks after the initiation of antifungal therapy was assessed. In addition, the correlation between the strain serotype and the in vitro activities of the antifungals was determined, and the susceptibility results obtained with the different techniques were also compared. Thirty-seven patients received a combination of amphotericin B with flucytosine as first-line therapy, 22 were treated with amphotericin B alone, and 15 received fluconazole alone. Whatever the antifungal tested, there was no trend toward higher MICs for strains isolated from patients who failed to respond to a given therapy compared to those from patients who did not with either the CLSI method, Etest, or broth microdilution in YNB medium. The MICs obtained by the CLSI or Etest method were significantly lower for serotype D strains than for serotype A strains for both fluconazole and amphotericin B, while flucytosine MICs were not different according to serotype. These findings suggest that the in vitro antifungal susceptibility of C. neoformans, as determined with the techniques used, is not able to predict the early clinical outcome in patients with cryptococcosis.

The members of the French Cryptococcosis Study Group are listed in Acknowledgments.

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