Malerczyk C, Kolbert M, Kinzig-Schippers M, Sörgel F, Machka K, Shah P M
Institut für Pharmakologie, Philipps Universität, D-35033 Marburg, Germany.
J Chemother. 2004 Feb;16(1):56-61. doi: 10.1179/joc.2004.16.1.56.
The objective of this study was to determine serum bactericidal titers (SBT, the highest dilution of serum showing no growth) and the serum bactericidal activity (SBA, i.e. duration of SBT greater than 1:2) as well as the serum bactericidal rate of gemifloxacin and clarithromycin after single doses in healthy male volunteers against Streptococcus pneumoniae. Strains tested had various degrees of susceptibility to penicillin as well as different susceptibility to quinolones due to a different QRDR mutation pattern (parC, gyrA). Serum samples from volunteers (n = 12) who had received a single oral dose of either 320 mg gemifloxacin or 500 mg clarithromycin in an open-label crossover study were obtained over a 24-hour period. SBA was determined, using the microdilution method. SBA of wildtype strains for gemifloxacin ranged from 8.9 to 15.4 h (mean 12.6 h). For gemifloxacin, 2 strains with solitary gyrA mutation had an SBA from 4.5 to 4.7 h (median 4.5 h). One of the 2 strains with a single QRDR mutation in parC displayed an SBA of 4.5 h, comparable to the gyrA mutation strains, whereas the second strain had a nearly twice as long SBA of 8.9 h. Two strains with two mutations (parC and gyrA) did not display any SBA. For clarithromycin, the duration of SBA ranged from 11.3 to 15.5 h (mean 13.6 h) for 6 of the 12 strains with an MIC < or = 0.06 mg/L (no SBA was found for the remaining strains, with an MIC of 0.25 mg/L or higher). In conclusion, a correlation between individual serum concentrations and SBA was found for both antibiotics.
本研究的目的是测定健康男性志愿者单次服用吉米沙星和克拉霉素后对肺炎链球菌的血清杀菌滴度（SBT，即血清中无细菌生长的最高稀释度）、血清杀菌活性（SBA，即SBT大于1:2的持续时间）以及血清杀菌率。由于喹诺酮耐药决定区（QRDR）突变模式（parC、gyrA）不同，所测试的菌株对青霉素有不同程度的敏感性，对喹诺酮类药物也有不同的敏感性。在一项开放标签交叉研究中，从接受单次口服320 mg吉米沙星或500 mg克拉霉素的志愿者（n = 12）中获取24小时内的血清样本。采用微量稀释法测定SBA。吉米沙星野生型菌株的SBA范围为8.9至15.4小时（平均12.6小时）。对于吉米沙星，2株具有孤立gyrA突变的菌株的SBA为4.5至4.7小时（中位数4.5小时）。在parC中有单个QRDR突变的2株菌株中的1株显示SBA为4.5小时，与gyrA突变菌株相当，而第二株菌株的SBA几乎是其两倍，为8.9小时。2株具有两个突变（parC和gyrA）的菌株未显示任何SBA。对于克拉霉素，12株中6株MIC≤0.06 mg/L的菌株的SBA持续时间为11.3至15.5小时（平均13.6小时）（其余MIC为0.25 mg/L或更高的菌株未发现SBA）。总之，两种抗生素的个体血清浓度与SBA之间均存在相关性。
