Stearne Lorna E T, Buijk Steven L, Mouton Johan W, Gyssens Inge C
Department of Medical Microbiology and Infectious Diseases, Erasmus MC, The Netherlands.
Antimicrob Agents Chemother. 2002 Dec;46(12):3712-8. doi: 10.1128/AAC.46.12.3712-3718.2002.
The importance of supplementary imipenem therapy after a single percutaneous abscess drainage puncture was studied in a mouse model of established mixed-infection abscesses. Animals were treated for 3 days with daily dosing regimens of 384 to 1,536 mg/kg of body weight that took into account the short half-life of this antibiotic in mice. Imipenem therapy in conjunction with abscess drainage was significantly better than drainage alone in reducing the Escherichia coli and Bacteroides fragilis counts in the mixed infections. Furthermore, the killing of B. fragilis by the combination of imipenem therapy and abscess drainage was significantly better than that by imipenem treatment alone. The maximum reductions in E. coli and B. fragilis counts were 1.1 and 2.2 log(10) CFU/abscess, respectively. In contrast, the in vitro activity of imipenem was significantly better (maximum reduction, > or =6.2 log(10) CFU/ml) against mixed cultures of the same strains even when bacterial numbers similar to those found in the abscesses were used. Comparable in vivo activity was achieved only when treatment was started 30 min before inoculation (reduction for both strains, > or =6.1 log(10) CFU/abscess), but this killing was significantly diminished if the start of treatment was delayed until > or =12 h after inoculation. Imipenem concentrations in abscess tissue reached levels above the MIC for E. coli for >60% of the dosing interval. Possible reasons for the reduced activity of imipenem in vivo are discussed, and we conclude that standard susceptibility tests overestimate the efficacy of this antibiotic against the organisms present in these abscesses.
在已建立的混合感染性脓肿小鼠模型中,研究了单次经皮脓肿穿刺引流后补充亚胺培南治疗的重要性。考虑到该抗生素在小鼠体内的半衰期较短,动物接受了为期3天的治疗,每日给药剂量为384至1536mg/kg体重。在减少混合感染中的大肠杆菌和脆弱拟杆菌数量方面,亚胺培南治疗联合脓肿引流明显优于单纯引流。此外,亚胺培南治疗与脓肿引流联合使用对脆弱拟杆菌的杀灭效果明显优于单独使用亚胺培南治疗。大肠杆菌和脆弱拟杆菌数量的最大减少量分别为1.1和2.2 log(10) CFU/脓肿。相比之下,即使使用与脓肿中发现的细菌数量相似的细菌,亚胺培南对相同菌株混合培养物的体外活性也明显更好(最大减少量,≥6.2 log(10) CFU/ml)。只有在接种前30分钟开始治疗时才能获得相当的体内活性(两种菌株的减少量,≥6.1 log(10) CFU/脓肿),但如果治疗开始延迟至接种后≥12小时,这种杀灭效果会明显减弱。脓肿组织中亚胺培南浓度在给药间隔的60%以上时间达到高于大肠杆菌最低抑菌浓度的水平。文中讨论了亚胺培南体内活性降低的可能原因,我们得出结论,标准药敏试验高估了这种抗生素对这些脓肿中存在的微生物的疗效。