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Clinical Microbiology Reviews, April 2004, p. 268-280, Vol. 17, No. 2
0893-8512/04/$08.00+0     DOI: 10.1128/CMR.17.2.268-280.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Determination of Fungicidal Activities against Yeasts and Molds: Lessons Learned from Bactericidal Testing and the Need for Standardization

M. A. Pfaller,1* D. J. Sheehan,2 and J. H. Rex3

Department of Pathology and Epidemiology, University of Iowa College of Medicine and College of Public Health, Iowa City, Iowa,1 Pfizer Inc., New York, New York,2 Astrazeneca, Macclesfield, United Kingdom3

In certain unique clinical settings, the ability of the antimicrobial agent administered to kill the pathogen outright may be quite important. These situations invariably involve infection of a site not easily accessed by host defenses and/or of a structure with essential anatomic or physiologic function such as the heart (endocarditis), central nervous system (meningitis), or bone (osteomyelitis). Likewise, infections in immunosuppressed hosts, especially those who are neutropenic, are often thought to require microbicidal therapy. Proof of the cidal nature of an antimicrobial agent in vitro is tedious, complex, and fraught with error. Although several methods for assessing in vitro bactericidal activity have been standardized (NCCLS M26-A and M21-A), the clinical relevance of these determinations is questionable and the tests are performed infrequently in most laboratories. Most of the clinical data supporting the need for microbicidal therapy and testing have focused on bacterial infections. However, given the fact that most serious fungal infections occur in profoundly immunosuppressed individuals, it is generally assumed that a cidal regimen would be preferable in that setting as well. In view of this clinical concern and the perceived need to assess the fungicidal activity of a variety of agents, we considered that it would be useful to review what is known about the issues and problems in assessing bactericidal activity and the clinical utility of such measurements. Following this review, we discuss the issue of how one defines fungicidal activity in vitro and in vivo and how feasible it might be to determine the fungicidal activity of organism-drug combinations for purposes of both drug development and clinical care. Proposed methods for fungal time-kill determinations and minimal fungicidal concentration determinations are also discussed.

* Corresponding author. Mailing address: Medical Microbiology Division, C606 GH, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242. Phone: (319) 384-9566. Fax: (319) 356-4916. E-mail: michael-pfaller{at}uiowa.edu.

Clinical Microbiology Reviews, April 2004, p. 268-280, Vol. 17, No. 2
0893-8512/04/$08.00+0     DOI: 10.1128/CMR.17.2.268-280.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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