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Antimicrobial Agents and Chemotherapy, February 1998, p. 282-288, Vol. 42, No. 2
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Evaluation of Possible Correlations between Antifungal Susceptibilities of Filamentous Fungi In Vitro and Antifungal Treatment Outcomes in Animal Infection Models

F. C. Odds,1,* F. Van Gerven,1 A. Espinel-Ingroff,2 M. S. Bartlett,3 M. A. Ghannoum,4 M. V. Lancaster,5 M. A. Pfaller,6 J. H. Rex,7 M. G. Rinaldi,8 and T. J. Walsh9,dagger

Department of Bacteriology and Mycology, Janssen Research Foundation, Beerse, Belgium1; Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia2; Indiana University Medical Center, Indianapolis, Indiana3; Center for Medical Mycology, Cleveland, Ohio4; Antimicrobial Resistance Section, Centers for Disease Control and Prevention, Atlanta, Georgia5; Special Microbiology Laboratory, University of Iowa College of Medicine, Iowa City, Iowa6; Division of Infectious Diseases, Department of Internal Medicine, Center for the Study of Emerging and Reemerging Pathogens, University of Texas Medical School, Houston, Texas7; Department of Pathology, University of Texas Health Science Center, San Antonio, Texas8; and Pediatric Branch, National Cancer Institute, Bethesda, Maryland9

Received 18 April 1997/Returned for modification 30 May 1997/Accepted 17 November 1997

Nine isolates of filamentous fungi previously tested in 11 different laboratories for their susceptibilities to amphotericin B and itraconazole in vitro were injected intravenously into mice and guinea pigs, and responses to treatment with both agents were studied. The experiments were done in a single laboratory. Mean survival times, the percentages of animals surviving 12 days after infection, and culture results for samples of deep organs obtained postmortem were used as markers of antifungal efficacy. Because of variations in organism pathogenicity, interpretable test systems in vivo could not be established for Fusarium spp. in mice or guinea pigs or for Pseudallescheria boydii in mice, even with the use of immunosuppressive pretreatments. Among the infections that could be evaluated, some degree of response to the corresponding treatment in vivo was seen in animals infected with each of two Rhizopus arrhizus isolates susceptible to amphotericin B at <0.5 µg/ml and Aspergillus spp. isolates susceptible to itraconazole at <1.0 µg/ml. Conversely, no responses were apparent with infecting strains for which MICs were >= 2 µg/ml (amphotericin B) or >= 1 µg/ml (itraconazole). However, the limitations of the intravenous challenge systems studied mean that no firm conclusion relating MICs in vitro to the lowest effective doses in vivo could be drawn.

* Corresponding author. Mailing address: Department of Bacteriology and Mycology, Janssen Research Foundation, B-2340 Beerse, Belgium. Phone: (32) 14-603004. Fax: (32) 14-605403. E-mail: fodds{at}janbelc1.ssw.jnj.com.

dagger For the Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards.

Antimicrobial Agents and Chemotherapy, February 1998, p. 282-288, Vol. 42, No. 2
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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