Date of Degree

2010

Document Type

PhD diss.

Degree Name

PhD (Doctor of Philosophy)

Department

Pharmacy

First Advisor

Erika J. Ernst

Abstract

With the recent emergence of candidemia as a significant cause of mortality in our health care system, clinicians must identify methods to minimize the sequelae of infection of this type in patients already burdened with serious underlying conditions. While well established as a major cause of blood stream infection (BSI), candidemia has been shown to have some of the highest rates of inappropriate therapy when compared to infections from all other sources. Rates of inappropriate therapy may be even higher for some of the less common and antifungal resistant non-albicans candidemia. Identifying those patients at risk for the development of these types of infections will help improve clinical outcomes. Antifungal activity is dependent both on species and agent, describing the unique susceptibility patterns between Candida species can help identify the appropriate therapy.

We performed a case-case-control study to identify clinical risk factors for the development of Candida glabrata candidemia compared to Candida albicans candidemia and an uninfected control using multivariate and logistic regression analysis. We observed that patients in the C. glabrata cohort were more likely to have gastrointestinal disorders and peripheral vascular disease than patients suffering from C. albicans BSIs. We also determined that when compared to the uninfected control group, patients with C. glabrata BSIs were more likely to have been prior colonized with C. glabrata, undergone dialysis, and have been catheterized with both arterial and urinary catheters. We concluded that patient exposure to unique clinical risk factors may be predictive of the development of future candidemia and may help distinguish between albicans versus non-albicans candidemia.

We performed a drug susceptibility study using time-kill methods with the echinocandin antifungal agents on Candida parapsilosis and two newly identified species of Candida, C. orthopsilosis and C. metapsilosis. The echinocandins as a group displayed primarily fungistatic activity against the clinical isolates tested. However, we observed substantial variability in antifungal activity that varied by both the echinocandin used and Candida species analyzed. We concluded that this variability in activity that is both species and drug dependent should be considered when selecting the treatment of candidemia resulting from these non-albicans species.

Pages

viii, 70

Bibliography

64-70

Copyright

Copyright 2010 Jesse Lee Hollanbaugh