Hassan I J, Stark R M, Greenman J, Millar M R
Pathology and Microbiology Department, University of Bristol, Bristol BS2 8HW, United Kingdom.
Antimicrob Agents Chemother. 1999 Jun;43(6):1387-92. doi: 10.1128/AAC.43.6.1387.
A continuous-culture system (chemostat) was used to study the activities of beta-lactam antimicrobial agents, clarithromycin, and 14-OH-clarithromycin against slowly growing Helicobacter pylori NCTC 11637. H. pylori was grown to steady state before exposure to these antimicrobial agents at x8 the MIC. The bactericidal actions of combinations of amoxicillin and clarithromycin were also studied. Viable counts (numbers of CFU per milliliter) were determined at 2-h intervals for 12 h and at 20 h after the addition of antibiotics. The effects of pH changes (6.5 to 7.4) on the activities of amoxicillin, clarithromycin, and the combination of these against H. pylori NCTC 11637 were also studied. Viable counts following exposure to ampicillin, cefixime, ceftazidime, cefuroxime, cefotaxime, azlocillin, and piperacillin at 20 h showed bacteriostatic activity. Imipenem, meropenem, amoxicillin, clarithromycin, and 14-OH-clarithromycin reduced the viable counts by 3 log10 CFU/ml (>/=99.9% killing). Imipenem was the most rapidly bactericidal against H. pylori NCTC 11637. Results of the pH experiments showed that amoxicillin was bactericidal at pHs 6.5 to 7. 4. Clarithromycin was bactericidal at pH 7.0 to 7.4 but was bacteriostatic at pH 6.5. The combination of amoxicillin and clarithromycin was bactericidal at pHs 6.5 and 7.0. A batch culture (flask system) was also used to investigate 12 strains of H. pylori for their susceptibilities to beta-lactams, clarithromycin, and/or 14-OH-clarithromycin in order to determine whether results from the chemostat model can be reproduced with batch cultures. Results of the chemostat time-kill kinetic study were reproducible in our batch culture flask system. The role of carbapenems in the eradication of H. pylori should be investigated.
采用连续培养系统（恒化器）研究β-内酰胺类抗菌药物、克拉霉素和14-羟基克拉霉素对缓慢生长的幽门螺杆菌NCTC 11637的活性。幽门螺杆菌在以8倍最低抑菌浓度（MIC）暴露于这些抗菌药物之前先培养至稳定状态。还研究了阿莫西林和克拉霉素联合用药的杀菌作用。在添加抗生素后，每隔2小时测定12小时内以及20小时时的活菌计数（每毫升菌落形成单位数）。还研究了pH变化（6.5至7.4）对阿莫西林、克拉霉素及其联合用药针对幽门螺杆菌NCTC 11637活性的影响。在20小时时，暴露于氨苄西林、头孢克肟、头孢他啶、头孢呋辛、头孢噻肟、阿洛西林和哌拉西林后的活菌计数显示出抑菌活性。亚胺培南、美罗培南、阿莫西林、克拉霉素和14-羟基克拉霉素使活菌计数降低3 log10 CFU/ml（杀菌率≥99.9%）。亚胺培南对幽门螺杆菌NCTC 11637的杀菌速度最快。pH实验结果表明，阿莫西林在pH 6.5至7.4时具有杀菌作用。克拉霉素在pH 7.0至7.4时具有杀菌作用，但在pH 6.5时具有抑菌作用。阿莫西林和克拉霉素联合用药在pH 6.5和7.0时具有杀菌作用。还采用分批培养（烧瓶系统）研究了12株幽门螺杆菌对β-内酰胺类药物、克拉霉素和/或14-羟基克拉霉素的敏感性，以确定恒化器模型的结果能否在分批培养中重现。恒化器时间-杀菌动力学研究的结果在我们的分批培养烧瓶系统中具有可重复性。应研究碳青霉烯类药物在根除幽门螺杆菌中的作用。
