Nephrotoxicity of Amoxicillin and Third-Generation Cephalosporins: An Updated Review

Because of their broad-spectrum bactericidal activity, amoxicillin (AMX) and third-generation cephalosporins (TGC) are widely used for the prophylaxis and treatment of established infections. They are considered relatively safe, but several recent reports have suggested substantial nephrotoxicity, especially with AMX use. Considering the importance of AMX and TGC for clinical practice, we conducted this up-to-date review, using the PubMed database, which focuses specifically on the nephrotoxicity of these molecules. We also briefly review the pharmacology of AMX and TGC. Nephrotoxicity of AMX may be driven by several pathophysiological mechanisms, such as a type IV hypersensitivity reaction, anaphylaxis, or intratubular and/or urinary tract drug precipitation. In this review, we focused on the two main renal adverse effects of AMX, namely acute interstitial nephritis and crystal nephropathy. We summarize the current knowledge in terms of incidence, pathogenesis, factors, clinical features, and diagnosis. The purpose of this review is also to underline the probable underestimation of AMX nephrotoxicity and to educate clinicians about the recent increased incidence and severe renal prognosis associated with crystal nephropathy. We also suggest some key elements on the management of these complications to avoid inappropriate use and to limit the risk of nephrotoxicity. While renal injury appears to be rarer with TGC, several patterns of nephrotoxicity have been reported in the literature, such as nephrolithiasis, immune-mediated hemolytic anemia, or acute interstitial nephropathy, which we detail in the second part of this review.