Lister P D, Pong A, Chartrand S A, Sanders C C
Center for Research in Anti-Infectives and Biotechnology, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Antimicrob Agents Chemother. 1997 Sep;41(9):1926-32. doi: 10.1128/AAC.41.9.1926.
To evaluate whether increased doses of amoxicillin should be used to treat acute pneumococcal otitis media, an in vitro pharmacokinetic model was used to evaluate the killing of pneumococci by amoxicillin when middle ear pharmacokinetics were simulated. Logarithmic-phase cultures were exposed to peak concentrations of 3, 6, and 9 microg of amoxicillin per ml every 12 h, and an elimination half-life of 1.6 h was simulated. Changes in viable bacterial counts were measured over 36 h. All three doses rapidly decreased the viable bacterial counts of penicillin-susceptible strains below the 10-CFU/ml limit of detection by 6 to 10 h and maintained counts below this limit through 36 h. The 3-microg/ml peak dose was much less effective against two of three strains with intermediate penicillin resistance and all three penicillin-resistant strains, with bacterial counts approaching those in drug-free control cultures by 12 h. The 6-microg/ml peak dose completely eliminated two of three strains with intermediate penicillin resistance and maintained viable counts of the other nonsusceptible strains at 1.5 to 2 logs below the initial inoculum through 36 h. The 9-microg/ml peak dose was most effective, completely eliminating all three strains with intermediate penicillin resistance and maintaining the viable counts of the resistant strains at 3 to 4 logs below the original inoculum. The pharmacodynamics observed in this study suggest that peak concentrations of amoxicillin of 6 to 9 microg/ml may be sufficient for the elimination of penicillin-nonsusceptible pneumococcal strains causing otitis media, especially those with intermediate resistance to amoxicillin. In vivo pharmacokinetic studies are needed to determine if these levels can be achieved in middle ear fluid with amoxicillin at 70 to 90 mg/kg/day divided into two daily doses. If these levels are reliably achieved, then clinical studies are warranted.
为评估是否应使用更高剂量的阿莫西林来治疗急性肺炎球菌性中耳炎，研究人员采用体外药代动力学模型，在模拟中耳药代动力学的情况下评估阿莫西林对肺炎球菌的杀菌效果。对数期培养物每12小时暴露于浓度分别为3、6和9微克/毫升的阿莫西林峰值浓度下，并模拟消除半衰期为1.6小时的情况。在36小时内测量活菌数的变化。所有三种剂量均能在6至10小时内迅速将青霉素敏感菌株的活菌数降至10 CFU/毫升的检测限以下，并在36小时内维持该水平以下。3微克/毫升的峰值剂量对三株青霉素中度耐药菌株中的两株以及所有三株青霉素耐药菌株的效果要差得多，到12小时时细菌数量接近无药对照培养物中的数量。6微克/毫升的峰值剂量完全清除了三株青霉素中度耐药菌株中的两株，并在36小时内将其他不敏感菌株的活菌数维持在比初始接种量低1.5至2个对数的水平。9微克/毫升的峰值剂量最有效，完全清除了所有三株青霉素中度耐药菌株，并将耐药菌株的活菌数维持在比原始接种量低3至4个对数的水平。本研究中观察到的药效学表明，阿莫西林峰值浓度为6至9微克/毫升可能足以消除引起中耳炎的青霉素不敏感肺炎球菌菌株，尤其是那些对阿莫西林中度耐药的菌株。需要进行体内药代动力学研究，以确定每日分两次服用70至90毫克/千克的阿莫西林能否在中耳液中达到这些水平。如果能可靠地达到这些水平，那么就有必要进行临床研究。
