Significance of inducible cephalosporinase remaining in the experimentally infected rat granuloma pouch after beta-lactam therapy

Abstract

We studied the influence of inducible cephalosporinase on levels of secondarily administered beta-lactam antibiotics in exudates using experimentally infected rat granuloma pouches. Cefoperazone or cefmetazole was administered intramuscularly at a dose of 100 mg/kg of body weight to rats at 2 and 8 h after infection of rat pouches with Serratia marcescens W-24, which possesses an inducible type I beta-lactamase (cephalosporinase). Subsequently, cefotaxime or cefbuperazone was administered at an intravenous dose of 100 mg/kg to rats at 24 h postinfection. Levels of cefotaxime in the pouch exudates of the cefmetazole-pretreated group were lower than those in the control group, which was infected but not pretreated with antibiotics. This was due to the inactivation of cefotaxime by extracellular cephalosporinase which was induced by cefmetazole and which remained in the rat pouches. However, cefotaxime concentrations were not reduced in the cefoperazone-pretreated group because of the low inducibility of cefoperazone against cephalosporinase production. On the other hand, cefbuperazone concentrations were similar in all groups (control, cefoperazone pretreated, and cefmetazole pretreated), because cefbuperazone is more stable against this enzyme than cefotaxime is. In conclusion, concentrations of secondarily administered beta-lactam antibiotics are affected by inducibly produced cephalosporinase at the infection site when a good inducer like cefmetazole is administered beforehand.