Does nephrotoxicity develop less frequently when vancomycin is combined with imipenem-cilastatin than with meropenem? A comparative study

Abstract

Introduction: Nephrotoxicity is a frequent complication of vancomycin therapy. Experimental studies in different animal species have demonstrated the attenuation of vancomycin-associated nephrotoxicity with cilastatin administration. This study aimed to evaluate if imipenem-cilastatin attenuates vancomycin-associated nephrotoxicity, in patients treated with combinations of vancomycin and carbapenems. Methods: This retrospective, propensity-score matched study was conducted at King Faisal Specialist Hospital and Research Centre, Riyadh and Jeddah. Nephrotoxicity was compared in patients who received imipenem-cilastatin + vancomycin or meropenem + vancomycin. Patients with no history of renal disease who received imipenem-cilastatin + vancomycin or meropenem + vancomycin for a minimum of 72 h, from 1 January 2017 to 31 December 2017, were included. Nephrotoxicity was defined according to the RIFLE criteria (Risk, Injury, Failure, Loss, End-stage renal disease) if sustained for least 72 h. Results: A total of 227 patients were included in the analysis, consisting of 121 patients in the imipenem-cilastatin + vancomycin group, and 106 patients in the meropenem + vancomycin group. In the unmatched data set the rate of nephrotoxicity was 8.2% in imipenem-cilastatin + vancomycin group and 20.7% in the meropenem + vancomycin group (p =.007). Logistic regression analysis showed that imipenem-cilastatin + vancomycin therapy was associated with a 56% lower rate of nephrotoxicity compared to meropenem + vancomycin therapy. Propensity-score matching resulted in rates of nephrotoxicity of 6.2% and 17.1% in the imipenem-cilastatin + vancomycin group and the meropenem + vancomycin groups, respectively (p =.034). Conclusion: Vancomycin-associated nephrotoxicity developed less frequently when vancomycin was combined with imipenem-cilastatin than when combined with meropenem.