Kim K S, Bayer A S
J Antimicrob Chemother. 1987 Apr;19(4):475-85. doi: 10.1093/jac/19.4.475.
Although penicillin tolerance has been increasingly recognized among clinical isolates of many Gram-positive organisms, the significance of this phenomenon in vivo is not clear. The present study was performed to characterize penicillin-tolerant enterococci by several in-vitro parameters and to examine the significance in vivo in a rabbit model of infective endocarditis. Tolerant enterococci exhibited several characteristics which distinguished them from non-tolerant bacteria: significantly greater ratios of MIC to MBC of penicillin, resistance to penicillin-induced lysis and killing, and growth in areas of superinhibitory concentrations of penicillin upon transfer from penicillin gradient to penicillin-free plates. In-vivo studies of aortic valve endocarditis in rabbits treated with procaine penicillin G (300 mg/kg/day) revealed strikingly different responses between infections due to one tolerant and one non-tolerant strain. Animals infected with a tolerant enterococcus showed consistently greater bacterial counts in vegetations during ten days of therapy and significantly lower rates of vegetation sterilization. Serum penicillin levels were not significantly different between the two groups, but serum bactericidal titres were significantly lower for the tolerant than for the non-tolerant strains. These findings indicate that penicillin tolerance identified by several in-vitro criteria is a significant determinant of the in-vivo response of enterococci to penicillin therapy.
尽管在许多革兰氏阳性菌的临床分离株中，青霉素耐受性已越来越受到认可，但这一现象在体内的意义尚不清楚。本研究旨在通过几个体外参数来表征耐青霉素肠球菌，并在感染性心内膜炎的兔模型中研究其在体内的意义。耐受性肠球菌表现出一些与非耐受性细菌不同的特征：青霉素的最低抑菌浓度（MIC）与最低杀菌浓度（MBC）之比显著更高、对青霉素诱导的裂解和杀伤具有抗性，以及从含青霉素梯度的平板转移至不含青霉素的平板后，能在青霉素超抑制浓度区域生长。对用普鲁卡因青霉素G（300mg/kg/天）治疗的兔主动脉瓣心内膜炎进行的体内研究显示，由一株耐受性菌株和一株非耐受性菌株引起的感染之间存在显著不同的反应。感染耐受性肠球菌的动物在治疗的十天内，赘生物中的细菌数量始终更多，赘生物杀菌率显著更低。两组之间的血清青霉素水平无显著差异，但耐受性菌株的血清杀菌效价显著低于非耐受性菌株。这些发现表明，通过几个体外标准鉴定出的青霉素耐受性是肠球菌对青霉素治疗体内反应的一个重要决定因素。
