ACTIVITY OF AMOXICILLIN-CLAVULANATE AGAINST PENICILLIN-RESISTANT STREPTOCOCCUS-PNEUMONIAE IN AN EXPERIMENTAL RESPIRATORY-INFECTION MODEL INRATS

High doses of amoxicillin, equivalent to those produced by 500- and 75 0-mg oral doses in humans (area under the plasma concentration-time cu rve), were effective against a penicillin-resistant strain of Streptoc occus pneumoniae in an experimental respiratory tract infection in imm unocompromised rats; this superior activity confirms the results of pr evious studies. An unexpected enhancement of amoxicillin's antibacteri al activity in vivo against penicillin-resistant and -susceptible S. p neumoniae strains was observed when subtherapeutic doses of amoxicilli n were coadministered with the beta-lactamase inhibitor potassium clav ulanate. The reason for this enhancement was unclear since these organ isms do not produce beta-lactamase. The differential binding of clavul anic acid and amoxicillin to penicillin-binding proteins may have cont ributed to the observed effects.