Thirteen-year evolution of azole resistance in yeast isolates and prevalence of resistant strains carried by cancer patients at a large medical center.

Drug resistance is emerging in many important microbial pathogens, including Candida albicans. We performed fungal susceptibility tests with archived isolates obtained from 1984 through 1993 and fresh clinical isolates obtained from 1994 through 1997 by testing their susceptibilities to fluconazole, ketoconazole, and miconazole and compared the results to the rate of fluconazole use. All isolates recovered prior to 1993 were susceptible to fluconazole. Within 3 years of widespread azole use, we detected resistance to all agents in this class. In order to assess the current prevalence of resistant isolates in our hematologic malignancy and transplant patients, we obtained rectal swabs from hospitalized, non-AIDS, immunocompromised patients between June 1995 and January 1996. The swabs were inoculated onto sheep's blood agar plates containing 10 microg of vancomycin and 20 microg of gentamicin/ml of agar. One hundred one yeasts were recovered from 97 patients and were tested for their susceptibilities to amphotericin B, fluconazole, flucytosine, ketoconazole, and miconazole. The susceptibility pattern was then compared to those for all clinical isolates obtained throughout the medical center. The antifungal drug histories for each patient were also assessed. The yeasts from this surveillance study were at least as susceptible as the overall hospital strains. There did not appear to be a direct linkage between prior receipt of antifungal agent therapy and carriage of a new, drug-resistant isolate. Increased resistance to newer antifungal agents has occurred at our medical center, but it is not focal to any high-risk patient population that we studied. Monitoring of susceptibility to antifungal agents appears to be necessary for optimizing clinical therapeutic decision making.

Expression of p53 protein in precursor lesions and adenocarcinoma of human pancreas.

To evaluate the incidence and stage at which p53 alterations occur in human pancreatic carcinogenesis, we examined primary and metastatic carcinomas, carcinoma in situ, and hyperplastic lesions with and without atypia for p53 protein overexpression by immunohistochemical procedure. Overexpression of p53 was observed in 40% (10/25) of primary tumors, 29% (2/7) of metastatic tumors, 36% (5/14) of carcinoma in situ, and 35% (6/17) of hyperplastic lesions. These results suggest that p53 protein overexpression is not only a common genetic alteration but also occurs very early in the development of these tumors. It is suggested that p53 overexpression can be used as a marker to identify precursor lesions that have increased potential to develop into malignant tumors.