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Antimicrobial Agents and Chemotherapy, June 2000, p. 1544-1548, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Correlation of Fluconazole MICs with Clinical
Outcome in Cryptococcal Infection
A. I.
Aller,1
E.
Martin-Mazuelos,1,*
F.
Lozano,1
J.
Gomez-Mateos,1
L.
Steele-Moore,2
W. J.
Holloway,2
M. J.
Gutiérrez,1
F. J.
Recio,1 and
A.
Espinel-Ingroff3
Service of Microbiology and Unit of
Infectious Diseases, Valme University Hospital, Seville,
Spain1; Christiana Care, Infectious
Disease Lab, Wilmington, Delaware2; and
Medical College of Virginia, Virginia Commonwealth
University, Richmond, Virginia3
Received 29 April 1999/Returned for modification 16 June
1999/Accepted 6 March 2000
We have correlated the in vitro results of testing the
susceptibility of Cryptococcus neoformans to fluconazole
with the clinical outcome after fluconazole maintenance therapy in
patients with AIDS-associated cryptococcal disease. A total of 28 isolates of C. neoformans from 25 patients (24 AIDS
patients) were tested. The MICs were determined by the broth
microdilution technique by following the modified guidelines described
in National Committee for Clinical Standards (NCCLS) document M27-A,
e.g., use of yeast nitrogen base medium and a final inoculum of
104 CFU/ml. The fluconazole MIC at which 50% of isolates
are inhibited (MIC50) and MIC90, obtained
spectrophotometrically after 48 h of incubation, were 4 and 16 µg/ml, respectively. Of the 25 patients studied, 4 died of active
cryptococcal disease and 2 died of other causes. Therapeutic failure
was observed in five patients who were infected with isolates for which
fluconazole MICs were
16 µg/ml. Four of these patients had
previously had oropharyngeal candidiasis (OPC); three had previously
had episodes of cryptococcal infection, and all five treatment failure
patients had high cryptococcal antigen titers in either serum or
cerebrospinal fluid (titers, >1:4,000). Although 14 of the 18 patients
who responded to fluconazole therapy had previously had OPC infections,
they each had only a single episode of cryptococcal infection. It
appears that the clinical outcome after fluconazole maintenance therapy
may be better when the infecting C. neoformans strain is
inhibited by lower concentrations of fluconazole for eradication (MICs,
<16 µg/ml) than when the patients are infected with strains that
require higher fluconazole concentrations (MICs,
16 µg/ml). These
findings also suggest that the MICs determined by the modified NCCLS
microdilution method can be potential predictors of the clinical
response to fluconazole therapy and may aid in the identification of
patients who will not respond to fluconazole therapy.
*
Corresponding author. Mailing address: S. Microbiología, Hospital de Valme, Ctra Cádiz s/n 41014, Seville, Spain. Phone: 5-4596352. Fax: 5-4596395. E-mail:
micemm{at}valme.sas.cica.es.
Antimicrobial Agents and Chemotherapy, June 2000, p. 1544-1548, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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