Nephrotoxicity of aminoglycosides and cephalosporins in combination

Early clinical studies with combined cephaloridine and aminoglycoside therapy suggested that a synergistic nephrotoxic interaction was possible between agents in these two classes of antimicrobial drugs. The most compelling evidence supports a synergistic interaction between cephalothin and gentamicin or tobramycin. The documentation for interactions between other cephalosporin-aminoglycoside combinations is not as substantial as with cephalothin, but numerous case reports and clinical studies suggest the possibility of an enhanced nephrotoxic interaction with such regimens. Numerous factors may increase the likelihood of an apparent synergistic nephrotoxic aminoglycoside-cephalosporin interaction. In many cases where potentiation of drug-induced nephrotoxicity has been reported, patients were critically ill, and the underlying pathophysiological condition might have contributed to the resultant renal dysfunction. In addition, nephrotoxicity has been observed more frequently when very large doses of the cephalosporin were used in the combination therapy. Patients receiving cephalosporin-aminoglycoside therapy are also often being given other drugs that have the ability to damage the kidney (e.g. anticancer agents) or drugs that are known to enhance the nephrotoxic potential of the antimicrobial drugs (e.g. loop diuretics). Therefore, attention must be given to numerous factors in order to minimize the possibility of renal dysfunction developing with combination therapy. The question as to which drug is potentiating the nephrotoxic potential of the other remains to be answered. Although some investigators have suggested that the cephalosporin potentiates the effects of the aminoglycoside, others feel that the reverse is true. Data from the rabbit tend to support aminoglycoside potentiation of cephalosporin-induced nephrotoxicity. Resolution of this problem may, however, have to await the development of a more suitable animal model of the interaction. In addition, a better understanding of the pharmacokinetic interactions between cephalosporins and aminoglycosides and a more precise description of the mechanisms of nephrotoxicity induced by these agents could help uncover the answers to many of these questions. The development of newer antimicrobial drugs with broader microbial coverage and a lesser nephrotoxic potential than agents currently in use may reduce the need for combining cephalosporins and aminoglycoside or provide safer drug combinations for many clinical situations.(ABSTRACT TRUNCATED AT 400 WORDS)