Studies in vivo on the killing rate and refractory period of penicillin V in an experimental streptococcal infection

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Abstract
The refractory period and the killing rate of β-haemolytic streptococci after exposure to phenoxymethylpenicillin were tested in an in-vivo model. β-Haemolytic streptococci were injected into steel net chambers implanted subcutaneously on the backs of rabbits. The rabbits were treated with infusions of phenoxymethylpenicillin, either as a single dose to measure the refractory period or as repeated doses in order to measure the killing rate of streptococci. The peak concentration of phenoxymethylpenicillin in tissue chamber fluid occurred about 16–120min post infusion, and reached 0·4mg/l in infected and 0·6mg/l in uninfected tissue cage fluid. In the tissue cage fluid the phenoxymethylpenicillin concentration exceeded 0·03 mg/l, the MIC-value for the streptococcal strain used, for at least 6 h. After a single infusion there was a decline in viable count. The bacteria did not reach their original numbers until 60–70 h later. After the sixth infusion streptococci were no longer detectable in tissue cage fluid. There was a close correlation between viable counts before treatment and the time required for eradication of bacteria. L-phase variants of β-haemolytic streptococci were not found when tissue cage fluid was plated on special media.