Department of Clinical Microbiology, Royal University Hospital and Saskatoon Health Region, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Departments of Pathology and Ophthalmology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Department of Clinical Microbiology, Royal University Hospital and Saskatoon Health Region, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Int J Antimicrob Agents. 2015 Jun;45(6):594-9. doi: 10.1016/j.ijantimicag.2014.12.034. Epub 2015 Feb 16.
Streptococcus pneumoniae continues to be a significant respiratory pathogen, and increasing antimicrobial resistance compromises the use of β-lactam and macrolide antibiotics. Bacterial eradication impacts clinical outcome, and bacterial loads at the site of infection may fluctuate. Killing of two macrolide- and quinolone-susceptible clinical S. pneumoniae isolates by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin against varying bacterial densities was determined using the measured minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). For kill experiments, 10(6)-10(9) CFU/mL were exposed to the drug and were sampled at 0, 0.5, 1, 2, 3, 4, 6, 12 and 24 h following drug exposure. The log(10) reduction and percent reduction (kill) of viable cells was recorded. MICs and MPCs (mg/L) for azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin were 0.063-0.125/0.5-1, 0.031-0.063/0.25-0.5, 0.063/0.25-0.5, 0.008/0.016 and 0.031/0.25, respectively. Killing 10(6)-10(9) CFU/mL of bacteria by the drug MIC yielded incomplete killing, however log10 reductions occurred by 12 h and 24 h for all drugs. Exposure of 10(6)-10(9) CFU/mL to MPC drug concentrations resulted in the following log(10) reduction by 6h of drug exposure: azithromycin, 1.3-3.9; clarithromycin, 1.9-5.8; erythromycin, 0.8-4.7; telithromycin, 0.3-1.7; and gemifloxacin, 1.8-4.2. Bacterial loads at the site of infection may range from 10(6) to 10(9), and kill experiments utilising a higher bacterial inoculum provided a more accurate measure of antibiotic performance in high biomass situations. Killing was slower with telithromycin. Kill was greater and fastest with MPC versus MIC drug concentrations.
肺炎链球菌仍然是一种重要的呼吸道病原体，抗菌药物耐药性的增加影响了β-内酰胺类和大环内酯类抗生素的使用。细菌清除率影响临床转归，感染部位的细菌载量可能会波动。使用测定的最低抑菌浓度（MIC）和突变预防浓度（MPC），测定了阿奇霉素、克拉霉素、红霉素、泰利霉素和加替沙星对两种大环内酯类和喹诺酮类敏感的临床肺炎链球菌分离株在不同细菌密度下的杀菌作用。对于杀菌实验，将 10(6)-10(9) CFU/mL 的细菌暴露于药物中，并在药物暴露后 0、0.5、1、2、3、4、6、12 和 24 小时进行采样。记录活细胞的对数减少和百分比减少（杀菌）。阿奇霉素、克拉霉素、红霉素、泰利霉素和加替沙星的 MIC 和 MPC（mg/L）分别为 0.063-0.125/0.5-1、0.031-0.063/0.25-0.5、0.063/0.25-0.5、0.008/0.016 和 0.031/0.25。药物 MIC 杀灭 10(6)-10(9) CFU/mL 的细菌导致不完全杀菌，但所有药物在 12 小时和 24 小时时均发生对数减少。将 10(6)-10(9) CFU/mL 的细菌暴露于 MPC 药物浓度下，在 6 小时药物暴露时，以下药物的对数减少如下：阿奇霉素，1.3-3.9；克拉霉素，1.9-5.8；红霉素，0.8-4.7；泰利霉素，0.3-1.7；加替沙星，1.8-4.2。感染部位的细菌负荷可能在 10(6)到 10(9)之间，利用更高的细菌接种量进行杀菌实验可以更准确地衡量高生物量情况下抗生素的性能。泰利霉素的杀菌速度较慢。与 MIC 药物浓度相比，MPC 时的杀菌效果更好、速度更快。
