Abstract
Although PCN tolerance has been proposed as one possible explanation of the poor response of some cases of IE, the in vivo significance of this phenomenon is not clear. Therefore, we examined the importance of tolerance in the rabbit model of aortic valve IE. Tolerant (T) and non-tolerant (NT) E strains were identified in vitro by MBC/MIC ratios, timed-killing assays, autolysis and a penicillin gradient-replicate plate method.Procaine PCN, 6×105 units intramuscularly, twice daily, resulted in 1 hr serum levels of 19±2 and 25±5 μg/ml in NT and T groups, respectively. Vegetation titers and rates of vegetation sterilization at therapy days 0, 3, 6 and 10 are summarized below.Furthermore, 0/7 rabbits infected with T strain vs 4/5 with NT strain were cured by 10 days of PCN therapy (p<0.05).This study suggests that PCN tolerance may be a significant determinant in the in vivo response of E to penicillin.
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