Evaluating the Impact of Antibiotic Exposures as Time-Dependent Variables on the Acquisition of Carbapenem-Resistant Acinetobacter baumannii

Objectives: To determine the time-dependent effect of antibiotics on the initial acquisition of carbapenem-resistant Acinetobacter baumannii. Design: Retrospective cohort study. Setting: Forty-bed trauma ICU in Miami, FL. Patients: All consecutive patients admitted to the unit from November 1, 2010, to November 30, 2011. Interventions: None. Measurements and Main Results: Patients underwent surveillance cultures at admission to the unit and weekly thereafter. The primary outcome was the acquisition of carbapenem-resistant A. baumannii on surveillance cultures. Daily antibiotic exposures during the time of observation were used to construct time-dependent variables, including cumulative exposures (in grams and daily observed doses [defined daily doses]). Among 360 patients, 45 (12.5%) became colonized with carbapenem-resistant A. baumannii. Adjusted Cox models showed that each additional point in the Acute Physiologic and Chronic Health Evaluation score increased the hazard by 4.8% (hazard ratio, 1.048; 95% CI, 1.010-1.087; p = 0.0124) and time-dependent exposure to carbapenems quadrupled the hazard (hazard ratio, 4.087; 95% CI, 1.873-8.920; p = 0.0004) of acquiring carbapenem-resistant A. baumannii. Additionally, adjusted Cox models determined that every additional carbapenem defined daily dose increased the hazard of acquiring carbapenem-resistant A. baumannii by 5.1% (hazard ratio, 1.051; 95% CI, 1.007-1.093; p = 0.0243). Conclusions: Carbapenem exposure quadrupled the hazards of acquiring A. baumannii even after controlling for severity of illness.