Eagye Kathryn J, Kuti Joseph L, Nicolau David P
Center for Anti-Infective Research Development, Hartford Hospital, Hartford, CT 06102, USA.
Surg Infect (Larchmt). 2007 Apr;8(2):215-26. doi: 10.1089/sur.2006.025.
Selecting an appropriate agent for empiric antibiotic therapy for secondary peritonitis is challenging. The pathogens responsible, aerobic gram-negative bacilli in particular, are becoming more resistant to antibiotics. The purpose of this study was to predict the ability of common antimicrobial regimens to achieve optimal pharmacodynamic exposure against aerobic bacteria implicated in secondary peritonitis, while considering current national resistance trends.
Monte Carlo simulation was used to model pharmacodynamic endpoints and compare the cumulative fraction of response (CFR) for imipenem-cilastatin, meropenem, ertapenem, piperacillin/tazobactam, ceftazidime, ceftriaxone, ciprofloxacin, and levofloxacin against isolates of species associated with secondary peritonitis. Minimum inhibitory concentration (MIC) distributions for isolates collected in North America were obtained from the 2004 MYSTIC database. Pharmacokinetic parameters were derived from the literature; the endpoints evaluated included free drug time above the MIC (fT(>MIC)) and the area under the concentration-time curve to MIC ratio (AUC:MIC).
The simulation predicted that several compounds would have a superior probability of providing appropriate coverage of aerobic bacteria: Imipenem-cilastatin (98.6% CFR at 1 g q8h), meropenem (98.2% CFR at 1 g q8h), ertapenem (91.7% CFR at 1 g q24h), piperacillin/ tazobactam (93.7% CFR at 3.375 g q6h), ceftazidime (91.1% CFR at 2 g q8h), and cefepime (92.9% CFR at 1 g q12h and 95.8% CFR at 2 g q12h). Ceftriaxone, ciprofloxacin, and levofloxacin exhibited CFRs < 82%.
Considering contemporary susceptibility data for aerobic bacteria, monotherapy with any of the three carbapenems or piperacillin/tazobactam 3.375 g q6h would provide optimal exposure for the pathogens commonly encountered in secondary peritonitis. Cefepime (in combination with metronidazole to provide anti-anaerobic coverage) also would be an acceptable choice, as would ceftazidime given at 2 g q8h (again in combination with metronidazole). Despite the popularity of combination therapy based on ciprofloxacin, levofloxacin, or ceftriaxone with metronidazole, these choices appear to be inferior to the other options because of emerging antibiotic resistance, particularly in E. coli.
为继发性腹膜炎选择合适的经验性抗生素治疗药物具有挑战性。致病病原体，尤其是需氧革兰氏阴性杆菌，对抗生素的耐药性越来越强。本研究的目的是预测常用抗菌方案对继发性腹膜炎相关需氧菌实现最佳药效学暴露的能力，同时考虑当前全国的耐药趋势。
采用蒙特卡洛模拟对药效学终点进行建模，并比较亚胺培南 - 西司他丁、美罗培南、厄他培南、哌拉西林/他唑巴坦、头孢他啶、头孢曲松、环丙沙星和左氧氟沙星针对与继发性腹膜炎相关菌种分离株的累积反应分数（CFR）。从2004年MYSTIC数据库获取北美收集的分离株的最低抑菌浓度（MIC）分布。药代动力学参数来自文献；评估的终点包括高于MIC的游离药物时间（fT(>MIC)）和浓度 - 时间曲线下面积与MIC的比值（AUC:MIC）。
模拟预测几种化合物对需氧菌提供适当覆盖的概率较高：亚胺培南 - 西司他丁（1 g q8h时CFR为98.6%）、美罗培南（1 g q8h时CFR为98.2%）、厄他培南（1 g q24h时CFR为91.7%）、哌拉西林/他唑巴坦（3.375 g q6h时CFR为93.7%）、头孢他啶（2 g q8h时CFR为91.1%）和头孢吡肟（1 g q12h时CFR为92.9%，2 g q12h时CFR为95.8%）。头孢曲松、环丙沙星和左氧氟沙星的CFR < 82%。
考虑到需氧菌的当代药敏数据，三种碳青霉烯类药物中的任何一种或哌拉西林/他唑巴坦3.37 g q6h进行单药治疗可为继发性腹膜炎中常见的病原体提供最佳暴露。头孢吡肟（与甲硝唑联合以提供抗厌氧菌覆盖）也是一个可接受的选择，2 g q8h给予头孢他啶（同样与甲硝唑联合）也是如此。尽管基于环丙沙星、左氧氟沙星或头孢曲松与甲硝唑的联合治疗很常见，但由于新出现的抗生素耐药性，尤其是在大肠杆菌中，这些选择似乎不如其他选择。
