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Antimicrobial Agents and Chemotherapy, January 1998, p. 129-134, Vol. 42, No. 1
Division of Infectious Diseases, Department
of Internal Medicine, Center for the Study of Emerging and Reemerging
Pathogens, University of Texas Medical School, Houston, Texas
770301;
Division of Infectious Diseases,
Medical College of Virginia-VCU, Richmond, Virginia
232983; and
Section of Oncologic
Emergencies, Division of Hematology/Oncology, University of
Arkansas for Medical Sciences, Little Rock, Arkansas
772052
Received 7 July 1997/Returned for modification 12 August
1997/Accepted 17 October 1997
The trailing growth phenomenon seen when determining the
susceptibilities of Candida isolates to the azole
antifungal agents makes consistent endpoint determination difficult,
and the M27-A method of the National Committee for Clinical Laboratory
Standards addresses this problem by requiring an 80% reduction in
growth after 48 h of incubation. For some isolates, however, minor
variations of this endpoint criterion can produce up to 128-fold
variations in the resulting MIC. To investigate the significance of
this effect, isolates of Candida that exhibited various
forms of trailing growth when tested against fluconazole were
identified. The isolates were examined in a murine model of invasive
candidiasis and were ranked by their relative response to fluconazole
by using both improvement in survival and reduction in fungal burden in
the kidney. The resulting rank order of in vivo response did not match the MICs obtained by using the M27-A criterion, and these MICs significantly overestimated the resistance of three of the six isolates
tested. However, if the MIC was determined after 24 h of
incubation and the endpoint required a less restrictive 50% reduction
in growth, MICs which better matched the in vivo response pattern could
be obtained. Minor variations in the M27-A endpoint criterion are thus
required to optimize the in vitro-in vivo correlation for isolates that
demonstrate significant trailing growth when tested against
fluconazole.
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Optimizing the Correlation between Results of Testing In Vitro
and Therapeutic Outcome In Vivo for Fluconazole by Testing Critical
Isolates in a Murine Model of Invasive Candidiasis
*
Corresponding author. Mailing address: 6431 Fannin,
1728 JFB, Houston, TX 77030. Phone: (713) 500-6738. Fax: (713)
500-5495. E-mail: jrex{at}heart.med.uth.tmc.edu.
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