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It has been previously demonstrated that areas within the hospital that have the highest rates of antimicrobial resistance also have the highest rates of antimicrobial use (AU). The intensive care unit setting is one of the areas within the hospital that has the highest rate of antimicrobial use. Measures of hospital and unit specific AU is assuming increasing importance for understanding the dynamics of antimicrobial resistance at the population level. Data obtained from electronic order entry paired with antibiograms yielded a practical approach to analyze relationships between antibiotic usage and corresponding resistance. We found significant correlations with ciprofloxacin and tobramycin use and imipenem resistance. There was a nonstatistical correlation between imipenem use and imipenem resistance (r = 0.29 for 36 months) but it did indicate a positive correlation. There were also correlations in the pairings of drug and corresponding resistances—inverse correlation for ciprofloxacin use and ciprofloxacin resistance (r = -0.88) and a positive correlation with tobramycin use and tobramycin resistance (r = 0.93). Since changes in AU are paralleled by changes in the prevalence of resistance, application of these methods enable hospitals to monitor antibiotic stewardship program interventions with corresponding changes in the rate of resistance after implementation. Building upon the results from the ecological approach, explored the relationship of antimicrobial use, resistance patterns and risk factors pertinent to specific intensive care units. A case- control study was conducted utilizing patient isolates positive for P. aeruginosa (PA). Cases (n = 78) were patients with positive imipenem-resistant (IRPA) isolates from blood and respiratory cultures. Controls (n = 125) were patients with positive susceptible P. aeruginosa (SPA) isolates. Risk factors analyzed included prior antimicrobial use, comorbid conditions and demographic variables. Time at risk greater than 29 days (odds ration [OR], 3.1), ventilator (OR 6.5), prior hospitalization at another facility (OR 2.5), diabetes (OR 2.8), hospitalized due to an accident (OR 0.3), and prior linezolid use (OR 0.1) were associated with isolation of IRPA. Our final study analyzed the relationship of prior antimicrobial exposure and other risk factors for acquiring a multidrug-resistant strain of P aeruginosa (MDRPA). We chose a case-case-control design comparing patients with MDRPA isolates (n = 90) to tempero-spatially matched controls without a PA infection (n=273). Time at risk greater than 29 days (odds ration [OR], 13.11), ventilator (OR 6.10), bronchoscopy (OR 2.37), extended care facility stay (OR 3.39), BMI over 30 (OR 2.45), and receipt of blood products (OR 2.32) were associated with isolation of MDRPA. The second case group (n=108) consisted of patients with a susceptible P aeruginosa infection (SPA) compared with a second group of control patients (n=320). Time at risk 15 – 28 days (OR 2.05), ventilator (OR 3.19), bronchoscopy (OR 1.66), extended care facility stay (OR 2.19), BMI over 30 (OR 3.11), and receipt of blood products (OR 2.68) were associated with isolation of SPA.