优化亚胺培南-妥布霉素剂量方案对抗碳青霉烯类耐药鲍曼不动杆菌：中空纤维感染和数学建模的前瞻性验证。
Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling.
机构信息
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
出版信息
Antimicrob Agents Chemother. 2018 Mar 27;62(4). doi: 10.1128/AAC.02053-17. Print 2018 Apr.
Abstract
We aimed to prospectively validate an optimized combination dosage regimen against a clinical carbapenem-resistant (CRAB) isolate (imipenem MIC, 32 mg/liter; tobramycin MIC, 2 mg/liter). Imipenem at constant concentrations (7.6, 13.4, and 23.3 mg/liter, reflecting a range of clearances) was simulated in a 7-day hollow-fiber infection model (inoculum, ∼10 CFU/ml) with and without tobramycin (7 mg/kg q24h, 0.5-h infusions). While monotherapies achieved no killing or failed by 24 h, this rationally optimized combination achieved >5 log bacterial killing and suppressed resistance.
摘要
我们旨在前瞻性地验证一种优化的联合剂量方案，以对抗临床耐碳青霉烯（CRAB）分离株（亚胺培南 MIC，32 毫克/升；妥布霉素 MIC，2 毫克/升）。在 7 天的中空纤维感染模型（接种物，约 10 CFU/ml）中，以恒定浓度（反映清除范围的 7.6、13.4 和 23.3 毫克/升）模拟亚胺培南，并与妥布霉素（7 毫克/千克 q24h，0.5 小时输注）联合应用。虽然单药治疗在 24 小时内未达到杀菌或失败，但这种合理优化的联合治疗方案实现了>5 对数的细菌杀伤并抑制了耐药性。
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