Aminoglycoside Antibiotics and Cephalosporins
The nephrotoxic effects of gentamicin and tobramycin can be increased by the concurrent use of cephalothin. This may possibly be true for other aminoglycosides.
Clinical evidence
A randomized double-blind trial in patients with sepsis showed the following incidence of definite nephrotoxicity: gentamicin + cephalothin 30% (seven of 23); tobramycin + cephalothin 21% (five of 24); gentamicin + methicillin 10% (two of 20); tobramycin + methicillin 4% (one of 23).
A very considerable number of studies and case reports confirm this increase in the incidence of nephrotoxicity when gentamicin or tobramycin are used with cephalothin. However the opposite conclusion has been reached by a few others. Cefuroxime and cefotaxime are reported not to increase the nephrotoxic effects of tobramycin. Hypo-kalaemia has also been described in patients taking cytotoxic drugs for leukaemia when they were given gentamicin and cephalexin.
Mechanism
Uncertain. The nephrotoxic effects of gentamicin and tobramycin are well documented and it appears that these effects can be additive with cephalothin in some patients. Doses which are well tolerated separately can be nephrotoxic when given together.
Importance and management
The weight of evidence is that this is a potentially serious interaction. The gentamicin-cephalothin interaction is very well documented, but there is less information about tobramycin with cephalothin. The risk of nephrotoxicity is probably greatest if high doses are used in those with some existing renal impairment. Concurrent use is not totally contraindicated (see the report cited above1) but renal function should be very closely monitored and dosages kept to a minimum. This drug combination is probably best avoided in high risk patients wherever possible. Possible alternatives with a much reduced risk of nephrotoxicity are gentamicin or tobramycin with methicillin, or tobramycin with cefuroxime and cefotaxime. Whether other aminoglycosides interact similarly is uncertain, but the possibility should be borne in mind.
