Variation in electrophoretic karyotype and antifungal susceptibility of clinical isolates of Cryptococcus neoformans at a university-affiliated teaching hospital from 1987 to 1994

Ninety-eight isolates of Cryptococcus neoformans were collected from 30 patients at the University of Iowa Hospitals and Clinics from December 1987 through December 1994, The susceptibility of each isolate was determined against fluconazole, itraconazole, amphotericin B, and flucytosine. Of the 98 isolates, 53 were recovered from blood, 19 were recovered from cerebrospinal fluid (CSF), and 26 were recovered from other sources. Although the strains were isolated from the same institution, DNA typing by electrophoretic karyotype (EK) revealed wide genetic variation. Overall, 23 different EK profiles were identified by computer-aided analysis. An isolate exhibiting a single EK was isolated from 24 of 30 patients (80%), whereas multiple strains with unique EKs were isolated from 6 of 30 (20%) patients, Of the six patients who had multiple strains recovered, only one individual had two strains isolated from unique body sites, one strain from the blood and the other from the CSF, Six strains were isolated from multiple patients. Nine patients had multiple sequential isolates recovered over periods of time ranging from 3 days to 4 months. EK analysis revealed persistence of the same genotype in six of the cases. Three patients, however, appeared to have an isolate with a second distinct EK emerge during therapy. Of the patients with sequential positive cultures, an increase in the MICs for test agents was observed in only one case. C. neoformans isolates were collected over a period of 7 years, during which time MICs at our institution remained stable.