Date Approved

2012

Degree Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department

Health Sciences

Committee Member

Stephen Sonstein Ph.D, Chair

Committee Member

Keith S. Kaye, MD, MPH

Abstract

Background: Staphylococcus aureus is still considered one of the most significant human pathogens in terms of morbidity, mortality, and costs. Vancomycin should be avoided if possible for the treatment of MRSA when the Minimum Inhibiting Concentration (MIC) to Vancomycin is 2μg/mL, as it poses a therapeutic challenge. Main therapeutic options include Daptomycin and Linezolid, two new, expensive drugs, and trimethoprim/sulfamethoxazole(TMP/SMX), an old, inexpensive agent. Study aims were to compare the clinical efficacy and potential cost savings associated with TMP/SMX use.

Methods: A retrospective study was conducted at Detroit Medical Center. For calendar year 2009, unique adult patients (>18 years) with infections due to MRSA with MIC to Vancomycin of 2 μg/mL were included if they received ≥2 doses of TMP/SMX and/or Daptomycin and/or Linezolid. Data were abstracted from patient charts and pharmacy records.

Results: There were 328 patients included in study cohort; 143 received TMP/SMX alone, 89 received Daptomycin alone, 75 received Linezolid alone, and 21 patients received a combination therapy. In bivariate analysis, patients on TMP/SMX had significantly better outcomes, including in-hospital (p=0.003) and 90-day mortality (p<0.001). Patients on TMP/SMX were also younger (p<0.001), with less co-morbidities (p<0.001), less severe disease states (p<0.001), and lower intervals to initiation of appropriate therapy (p=0.001). In multivariate models, both with/without the use of a propensity score, the association between TMP/SMX treatment and mortality was no longer significant, but ORs remained lower than 1. Cost savings of using TMP/SMX averaged $2,067 per patient. The susceptibility rate to TMP/SMX had significantly increased from 2005 to 2009, despite increased usage. Conclusions: TMP/SMX compared favorably with Linezolid and Daptomycin in terms of efficacy and mortality. Cost saving were enormous. TMP/SMX use should be considered, particularly for skin and soft-tissue infections, and even in severe disease states due to MRSA with elevated vancomycin MICs.

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