Fuursted K, Knudsen J D, Petersen M B, Poulsen R L, Rehm D
Department of Research and Development in Microbiology, Statens Serum Institut, Copenhagen, Denmark.
Antimicrob Agents Chemother. 1997 Apr;41(4):781-4. doi: 10.1128/AAC.41.4.781.
In this report, we present MIC, bactericidal activity, postantibiotic effect (PAE), and in vivo infectivity data for postantibiotic-phase pneumococci. We compared and evaluated penicillin G and six macrolides, erythromycin, azithromycin, clarithromycin, dirithromycin, roxithromycin, and spiramycin, against 10 strains of pneumococci with various levels of susceptibility to penicillin. All of the agents, except azithromycin, exhibited a bactericidal effect (a > or = 3 log10 decrease in the number of CFU per milliliter) after 4 h of exposure to a concentration equal to 10 times the MIC, displaying the following hierarchy: spiramycin = penicillin G = erythromycin = dirithromycin = clarithromycin = roxithromycin > azithromycin. The bactericidal rate of penicillin G was significantly lower for resistant strains (MIC, > or = 2 microg/ml), while bactericidal rates of macrolides were unaffected by penicillin susceptibility. A PAE was induced in all of the strains by all of the antibiotics after exposure for 1 h to a concentration equivalent to 10 times the MIC. The mean duration of PAEs varied between 2.3 and 3.9 h, showing the following hierarchy: spiramycin = dirithromycin = clarithromycin = erythromycin = roxithromycin > azithromycin > penicillin G. Virulence studies were performed with immunocompetent mice by intraperitoneal inoculation of virulent, penicillin-susceptible serotype 3 pneumococci which had been pre-exposed to penicillin G or a macrolide for 1 h. A significant decrease in the virulence of postantibiotic-phase pneumococci was induced only by erythromycin, azithromycin, dirithromycin, and spiramycin, displaying 5.9-, 7.1-, 4.2-, and 3.6-fold increases in the 50% lethal dose (LD50) compared to a control suspension, respectively. No significant correlation could be demonstrated between the LD50 and the MIC, bactericidal activity, or PAE duration. These results suggest that antimicrobial interaction with host defenses in terms of virulence might be a significant parameter that could influence the drug or drug regimen of choice.
在本报告中，我们展示了抗生素后效应期肺炎球菌的最低抑菌浓度（MIC）、杀菌活性、抗生素后效应（PAE）以及体内感染性数据。我们比较并评估了青霉素G和六种大环内酯类药物，即红霉素、阿奇霉素、克拉霉素、地红霉素、罗红霉素和螺旋霉素，对10株对青霉素敏感性各异的肺炎球菌的作用。除阿奇霉素外，所有药物在暴露于等于10倍MIC的浓度4小时后均表现出杀菌作用（每毫升菌落形成单位数量减少≥3个对数级），呈现出以下排序：螺旋霉素 = 青霉素G = 红霉素 = 地红霉素 = 克拉霉素 = 罗红霉素 > 阿奇霉素。对于耐药菌株（MIC≥2μg/ml），青霉素G的杀菌率显著更低，而大环内酯类药物的杀菌率不受青霉素敏感性的影响。在所有菌株中，所有抗生素在暴露于等于10倍MIC的浓度1小时后均诱导出PAE。PAE的平均持续时间在2.3至3.9小时之间变化，呈现出以下排序：螺旋霉素 = 地红霉素 = 克拉霉素 = 红霉素 = 罗红霉素 > 阿奇霉素 > 青霉素G。通过对免疫功能正常的小鼠进行腹腔接种预先暴露于青霉素G或一种大环内酯类药物1小时的具有毒力、对青霉素敏感的3型肺炎球菌，开展了毒力研究。仅红霉素、阿奇霉素、地红霉素和螺旋霉素诱导出抗生素后效应期肺炎球菌的毒力显著降低，与对照悬液相比，50%致死剂量（LD50）分别增加了5.9倍、7.1倍、4.2倍和3.6倍。在LD50与MIC、杀菌活性或PAE持续时间之间未显示出显著相关性。这些结果表明，就毒力而言，抗菌药物与宿主防御的相互作用可能是一个重要参数，可能会影响所选药物或药物治疗方案。
