Affiliation:
1. Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio,1 and
2. Infectious Diseases Section, The Audie Murphy Memorial Veterans Hospital,2 San Antonio, Texas 78284
Abstract
ABSTRACT
A murine model of systemic candidiasis was used to assess the virulence of serial
Candida albicans
strains for which fluconazole MICs were increasing. Serial isolates from five patients with 17 episodes of oropharyngeal candidiasis were evaluated. The MICs for these isolates exhibited at least an eightfold progressive increase from susceptible (MIC < 8 μg/ml; range, 0.25 to 4 μg/ml) to resistant (MIC ≥ 16 μg/ml; range, 16 to ≥128 μg/ml). Virulence of the serial isolates from three of five patients showed a more than fivefold progressive decrease in the dose accounting for 50% mortality and was associated with development of fluconazole resistance. Low doses of fluconazole prolonged survival of mice infected with susceptible yeasts but failed to prolong survival following challenge with a resistant strain. In addition, a decreased burden of renal infection was noted in mice challenged with two of the three resistant strains. This was consistent with reduced virulence. Fluconazole did not further decrease the level of infection. In the isolates with a decrease in virulence, two exhibited overexpression of
CDR
, which encodes an ABC drug efflux pump. In contrast, serial isolates from the remaining two patients with the development of resistance did not demonstrate a change in virulence and fluconazole remained effective in prolonging survival, although significantly higher doses of fluconazole were required for efficacy. Resistant isolates from both of these patients exhibited overexpression of
MDR
. This study demonstrates that decreased virulence of serial
C. albicans
isolates is associated with increasing fluconazole MICs in some cases but not in others and shows that these low-virulence strains may not consistently cause infection.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
55 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献