The association between antibiotic use and resistance: the role of secondary antibiotics.

Using susceptibility rates of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae over time as markers, we assessed the significance of the change of susceptibility rates to imipenem, ceftriaxone, cefepime, piperacillin/tazobactam, and ciprofloxacin over time and the relationship to antibiotic use for the period 2000-2006. Antibiotic use-susceptibility relationships were assessed using longitudinal regression analysis. The variables "time" and define daily doses (DDD)/1,000 patient days for the specific drug related to the susceptibility rates of that particular model's dependent variable were considered as the main effects, with significance determined at the 0.05 level. Decreases in susceptibility of the target organisms were common over the period of observation. Decreasing susceptibility trends over time were not statistically associated with the primary drug (e.g., organism susceptibility rate to imipenem with imipenem usage). However, secondary drug use was associated with susceptibility rates (e.g., susceptibility of E. cloacae to cefepime with piperacillin/tazobactam usage). These results suggest that antibiotic use-resistance relationships are influenced by the use of secondary antibiotics. Thus, a resistance problem may not be adequately addressed by simply altering the utilization of the primary antibiotic.