Date of Award

2016

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Pharmaceutical Sciences

Department

Biomedical and Pharmaceutical Sciences

First Advisor

Aisling Caffrey

Abstract

The significant increase in antimicrobial resistance over the past few years is a serious global public health concern, particularly as the development of new antimicrobial agents had been slow for many years. Infections with resistant organisms are associated with poor clinical outcomes and higher cost burdens. Determining antimicrobial resistance patterns can help identify problem areas and modify treatment practices to improve clinical outcomes. Additionally, identifying adjunctive therapies can also help improve clinical outcomes among infected patients. The objectives, hypotheses, methods and results of this dissertation are threefold:

Manuscript 1: The objective was to analyze antimicrobial resistance trends in E. faecalis and E. faecium between 2003 and 2015 in five acute care facilities of the Veterans Affairs New England Healthcare System as antimicrobial resistance patterns among Enterococcus have changed over the past decade. Using a multicenter ecologic study design, we evaluated antimicrobial resistance patterns for blood and urine cultures of enterococci. In E. faecium urine cultures, a decline in gentamicin resistance, as well as a small decease in vancomycin resistance were observed. Enterococcus resistance towards ampicillin, linezolid, and tetracycline was stable over the study period. Daptomycin resistance did not emerge over the study period.

Manuscript 2: The objective was to evaluate the impact of statin exposure on clinical outcomes, including inpatient mortality and length of inpatient stay, among bacteremic patients. The hypothesis was that statin use would be associated with positive clinical outcomes compared to non-statin use. We conducted a retrospective cohort study using the deidentified Optum ClinformaticsTM (OptumInsight, Eden Prairie, MN) with matched Premier Hospital data (October 2009-March 2013). Our retrospective cohort study observed lower mortality for incident users and prevalent users continuing statin use during admission. Though non-significant in incident users, the point estimate was similar to that observed in other studies.

Manuscript 3: The objective was to identify a statin therapy duration among pre-defined baseline statin users at which use of statins minimizes the risk of inpatient mortality among bacteremic patients. The hypothesis was that a certain minimum duration of statin use during the hospitalization would improve survival. A casecontrol design was used to test this hypothesis using the Optum ClinformaticsTM with matched Premier Hospital data (October 2009-March 2013). Classification and regression tree analysis was conducted among cases and controls matched on disease risk scores. Among matched pairs of cases and controls with at least 90 days of pre-admission statin use, the continuation of statin use during admission for at least 2 days provided a better survival benefit among bacteremic patients.

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