Chapman S W, Steigbigel R T
J Infect Dis. 1983 Jun;147(6):1078-89. doi: 10.1093/infdis/147.6.1078.
The susceptibility of five cephalosporins and nafcillin to changes in inoculum size of 26 isolates of Staphylococcus aureus was studied. The spectrum of antibiotic sensitivity to such changes was cefazolin = cephaloridine greater than cefamandole greater than cephalothin greater than cefoxitin = nafcillin. Half of the isolates resulted in large and half in minimal inoculum-induced changes in minimal inhibitory concentrations (MICs). These changes correlated with the amount of beta-lactamase produced by the isolates. The in vivo relevance of these findings was studied in a model of intraperitoneal infection in mice. The effect of beta-lactamase production on mortality was greatest among animals given cefazolin or cephaloridine, intermediate among those given cefamandole, and nonexistent among those given cefoxitin, cephalothin, or nafcillin. The number of organisms in the animals' spleens paralleled survival rates. An increase in the serum level of cefazolin increased the survival rate among mice given that drug. Hence, the survival of mice was influenced by (1) the ability of the infecting organism to increase the MIC of an antibiotic via inoculum increases, (2) the sensitivity of the antibiotic to beta-lactamase, and (3) the peak level of antibiotic attained in serum.
研究了5种头孢菌素和萘夫西林对26株金黄色葡萄球菌接种量变化的敏感性。抗生素对这种变化的敏感性谱为：头孢唑林 = 头孢噻啶＞头孢孟多＞头孢噻吩＞头孢西丁 = 萘夫西林。一半的菌株导致最小抑菌浓度（MIC）出现较大的接种量诱导变化，另一半则导致最小变化。这些变化与菌株产生的β-内酰胺酶量相关。在小鼠腹腔感染模型中研究了这些发现的体内相关性。在给予头孢唑林或头孢噻啶的动物中，β-内酰胺酶产生对死亡率的影响最大，在给予头孢孟多的动物中影响中等，而在给予头孢西丁、头孢噻吩或萘夫西林的动物中则不存在影响。动物脾脏中的细菌数量与存活率平行。头孢唑林血清水平的升高增加了给予该药物的小鼠的存活率。因此，小鼠的存活受到以下因素影响：（1）感染菌通过增加接种量来提高抗生素MIC的能力；（2）抗生素对β-内酰胺酶的敏感性；（3）血清中达到的抗生素峰值水平。
