Journal of Antimicrobial Chemotherapy, Vol 41, 237-246, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
P Chavanet, F Dalle, P Delisle, M Duong, A Pechinot, M Buisson, P D'Athis and H Portier
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 log10 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.
ORIGINAL ARTICLES
Experimental efficacy of combined ceftriaxone and amoxycillin on penicillin-resistant and broad-spectrum cephalosporin-resistant Streptococcus pneumoniae infection
Service des Maladies Infectieuses, Microbiologie Medicale et Moleculaire (EA 562), Hopital du Bocage, Dijon, France.
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