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Abstract

Introduction: Critical illness is a known risk factor for nephrotoxicity as is exposure to aminoglycosides. The rate of nephrotoxicity comparing aminoglycosides to a control group is unknown using a standardized criterion such as RIFLE. Methods: A retrospective, cohort study of patients who received tobramycin or ciprofloxacin as part of empiric double gram-negative coverage in the SICU or MICU at a large academic medical center was performed. The choice of ciprofloxacin versus tobramycin was determined by hospital protocol which changed halfway through the study period. The primary outcome was the incidence of nephrotoxicity as defined by the RIFLE criteria within seven days of antibiotics. Secondary outcomes were length of hospital and ICU stay, hospital and ICU mortality, length of mechanical ventilation, incidence of Clostridium difficile, and initiation of renal replacement therapy. Categorical variables were compared using Chi-Square and continuous variables were compared by the Two-Sample t-Test or the Wilcoxon Rank-Sum Test depending on the distribution of the continuous variable. Results: A total of 263 patients received ciprofloxacin and 148 patients received tobramycin with similar baseline characteristics. The incidence of nephrotoxicity was 29.7% with ciprofloxacin and 33.1% with tobramycin (p=0.467). There was a significant difference in the number of patients requiring initiation of renal replacement therapy with 3.8% in the ciprofloxacin group and 8.8% in the tobramycin group (p=0.035). No other secondary outcomes were significantly different. In patients who received 4 to 5 concomitant nephrotoxic agents, there was a trend toward increased nephrotoxicity (p=0.076). A multivariable logistic regression was performed and no differences between the groups were found. Conclusions: No difference was found in the incidence of nephrotoxicity between tobramycin and ciprofloxacin in critically ill patients based on the RIFLE criteria. Tobramycin should be used cautiously in patients with multiple risk factors for nephrotoxicity as more patients who received tobramycin required renal replacement therapy. A prospective study is required to further characterize the risk of aminoglycoside nephrotoxicity in the critically ill.