Cefoxitin nephrotoxicity

The nephrotoxicity of cefotetan in rabbits was considerably less than that of cefazolin [50]. When compared to cefotiam, cefoxitin appears to be better tolerated by the kidney since the cefotiam-induced decrease of TEA accumulation and the decrease of gluconeogenesis in renal corhcal slices was 2-3 hmes greater than with cefoxitin [26]. 

More interesting, the presence of the thiophene ring in position 7 of the cephem nucleus (Figure 2) has been associated with nephrotoxic effects in the case of cephaloridine and cephalothin and to a lesser extent in the case of the cephamycin cefoxitin [26, 66]. When compared to cephalothin, small alterations of the cefoxitin molecule in positions 3 and 7 of the cephem nucleus, such as replacement of the methyl group with... 

The combination of cephalothin wifh an aminoglycoside was more nephrotoxic than methicillin plus aminoglycoside [143]. There is good evidence that concurrent administration of cephalothin and gentamicin are additive nephrotoxins in humans, especially in patients over 60 years of age as wells as in rabbits [144], and renal injuries are intensified in the presence of mild renal ischemia or endotoxemia [108]. The results of prospective randomized comparative studies of the combination mezlocillin/cefotaxime versus gentamicin/cefoxitin showed that the concurrent administration of mezlocillin/cefotaxime has low renal toxicity and can be recommended for the rational and empirical treatment of serious systemic infections [145]. 

The nephrotoxicity of various combinations of antibiotics was assessed in 171 cancer palienls. In Ihose receiving an aminoglycoside with a third generation cephalosporin, the most nephrotoxic combinations were found to be gentamicin with cefotaxime (although another study did not find this combination to be nephrotoxic ) and amikacin with ceftriaxone, where 5 of 20 and 5 of 13 patients, respectively, had increased serum creatinine. The following combinations were found to be safer amikacin with cefoxitin or ceftazidime, gentamicin with cefoxitin, and netilmicin with cefotaxime. ... 

Another study assessing the risk factors for nephrotoxicity with aminoglycosides (tobramycin and gentamicin) enrolled 1489 patients, 157 of whom developed clinical nephrotoxicity. Of these patients 118 had no immediately identifiable cause (such as acute renal failure) and further evaluation of other risk factors found that the concurrent use of cephalosporins (including cefazolin, cefotaxime, cefoxitin, cefamandole, ce-furoxime, ceftriaxone, and ceftazidime) significantly increased the risk of nephrotoxicity. ... 

The nephrotoxic effects of cefaloridine and possibly cefalotin or cefacetrile appear to be increased by furosemide. Cefradine brain levels are reduced by furosemide. No important interactions appear to occur between furosemide and cefoxitin, ceftazidime, ceftriaxone, or cefuroxime. 

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