| Background. Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent organism, causing serious infections which are difficult and expensive to treat. Despite the implementation of evidence-based infection control practices and development of newer efficacious antibiotics, MRSA infection and colonization rates continue to increase. Treatments for MRSA have received considerable research attention over the past 10 years, yet several gaps in knowledge remain. In particular, controversy regarding the effectiveness of linezolid as compared to vancomycin in treating MRSA infections persists, and few risk factors associated with mupirocin resistance have been identified.;Methods. In the first manuscript of this dissertation, we sought to estimate the effectiveness of linezolid compared to vancomycin on clinical outcomes, including length of hospital stay, mortality, length of therapy, and hospital readmission, among a national cohort of MRSA infected patients admitted to Veterans Affairs (VA) facilities. Propensity score adjusted Cox proportional hazards regression models quantified the effect of linezolid treatment compared to vancomycin in this retrospective cohort study. For the second manuscript, we conducted a frequency matched case-control study to identify independent predictors associated with mupirocin resistant MRSA among patients admitted to a VA medical center. In the last manuscript, we comprehensively reviewed the directed acyclic graph (DAG) methodology as a practical tool for confounding assessment in epidemiology and developed an applied infectious disease pharmacoepidemiologic example.;Findings. In the real-world clinical setting, linezolid therapy was associated with a significantly shorter length of stay (LOS) and significantly longer duration of therapy compared to vancomycin for the treatment of MRSA infections, while no differences were detected in the prevention of mortality or readmission. The median LOS was three days shorter among those treated with linezolid compared to vancomycin in our large national MRSA cohort. We identified four significant independent predictors associated with mupirocin resistant MRSA: (1) mupirocin exposure in the year prior to the culture date; (2) Pseudomonas aeruginosa infection in the year before the culture-related admission; (3) non-sterile culture site; and (4) cefepime utilization in the year prior to culture. Our applied example illustrates the utility of implementing DAG methods for confounding assessment in infectious disease pharmacoepidemiologic research. |
