Cephalosporin therapy for salmonellosis. Questions of efficacy and cross resistance with ampicillin.

The new cephalosporins should be explored for Salmonella septicemia efficacy, because of multiple-drug resistance, the high incidence of patient allergies to ampicillin and sulfamethoxazole-trimethoprim, and the limited number of antibiotics with proven efficacy. This study reports on six widely used cephalosporins: cephalothin, cefamandole, cefoperazone, cefoxitin, cefotaxime, and ceftriaxone with respect to in vitro killing of Salmonella. This in vitro activity was related to the stability of the agents to beta-lactamases. Cefoperazone was the least stable, followed by cefamandole and cephalothin. Cefoxitin, cefotaxime, and ceftriaxone were the most stable. The beta-lactamase-unstable agents permitted regrowth of beta-lactamase-producing salmonella within 36 hours. Standard susceptibility tests showed good inhibitory levels by these unstable agents at 18 hours, but the minimum inhibitory concentrations increased dramatically with longer incubation periods. Based on these results, past cephalothin failures for ampicillin-resistant Salmonella can be explained. Additionally, there should be a dichotomy of effectiveness in the new cephalosporins depending on their beta-lactamase stability. The stable cephalosporins deserve further clinical trials in the treatment of beta-lactamase-producing Salmonella infections.