Experimental efficacy of combined ceftriaxone and amoxycillin on penicillin-resistant and broad-spectrum cephalosporin-resistant Streptococcus pneumoniae infection

The activity of amoxycillin and ceftriaxone, alone and in combination, was tested against four strains of penicillin-resistant pneumococci in vitro and in an animal model. Three of the strains were also resistant to third-generation cephalosporins. Fractional inhibitory concentration indexes for combined amoxycillin and ceftriaxone were measured by the Etest method and were considered additive (1.2; 1.1; 1.3 and 1.3 for the four strains). Twenty-four hour time-kill curves for two strains showed that the combination was additive or synergic for concentrations up to the MIC of the single drugs. The efficacy of these antibiotics alone and in various combinations against strains 16089 and 11724 were investigated in vivo using prolonged (48 h) experimental fibrin clot infection in rabbits. The bacterial reductions (Delta log(10) cfu/g) obtained for all the antibiotic combinations tested were significantly higher than those of the single drug regimens. The in-vivo efficacy of amoxycillin was significantly correlated with the time for which its concentration was above the MIC and that of ceftriaxone was correlated with its maximal concentration. From these findings, we concluded that, at concentrations easily achievable in humans, the combination of amoxycillin and ceftriaxone was strongly synergic against infection due to penicillin- and cephalosporin-resistant pneumococci.