Impact of Bolus Dosing versus Continuous Infusion of Piperacillin and Tazobactam on the Development of Antimicrobial Resistance in Pseudomonas aeruginosa
Impact of Bolus Dosing versus Continuous Infusion of Piperacillin and Tazobactam on the Development of Antimicrobial Resistance in Pseudomonas aeruginosa
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DOI：
10.1128/aac.00867-13
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发表时间：
2013-12-01
影响因子：
4.9
通讯作者：
Hope, W. W.
中科院分区：
文献类型：
--
作者：
Felton, T. W.;Goodwin, J.;Hope, W. W.
医院肺炎的治疗常常因细菌耐药性而变得复杂。 β-内酰胺的延长输注越来越多地用于改善临床结果。然而，这种策略对抗菌素耐药性出现的影响尚不清楚。使用铜绿假单胞菌（PAO1）的中空纤维感染模型。经过 5 天的模拟，哌拉西林-他唑巴坦的药代动力学 (PK) 曲线与人体相似。在 0.5 小时或 4 小时内给予 3 剂哌拉西林-他唑巴坦，每 8 小时重新给药。研究了两种初始细菌密度（类似于 10(4) CFU/ml 和类似于 10(7) CFU/ml）。确定总细菌种群和耐药亚种群的时间进程。所有数据均使用数学模型进行描述，然后用于定义药物浓度、细菌杀灭和哌拉西林耐药性出现之间的关系。对照组在最初 24 小时内出现对数生长，达到类似于 9 log(10) CFU/ml 的平台。通过推注给药哌拉西林后的细菌杀灭效果与长期输注后的细菌杀灭效果相似。对于较低的初始细菌密度，推注和延长输注方案的总血浆哌拉西林浓度/MIC比率分别为3.4和10.4，能够抑制哌拉西林耐药性的出现。对于较高的初始细菌密度，所有方案都与耐药亚群的逐渐生长相关。治疗医院肺炎患者需要根据细菌密度采取分层方法。对于某些患者来说，抗生素单一疗法可能就足够了。然而，对于细菌负荷高的患者，需要替代治疗策略以最大限度地杀灭细菌并防止抗菌素耐药性。
Management of nosocomial pneumonia is frequently complicated by bacterial resistance. Extended infusions of beta-lactams are increasingly being used to improve clinical outcomes. However, the impact of this strategy on the emergence of antimicrobial resistance is not known. A hollow-fiber infection model with Pseudomonas aeruginosa (PAO1) was used. Pharmacokinetic (PK) profiles of piperacillin-tazobactam similar to those in humans were simulated over 5 days. Three dosages of piperacillin-tazobactam were administered over 0.5 h or 4 h, with redosing every 8 h. Two initial bacterial densities were investigated (similar to 10(4) CFU/ml and similar to 10(7) CFU/ml). The time courses of the total bacterial population and the resistant subpopulation were determined. All data were described using a mathematical model, which was then used to define the relationship between drug concentrations, bacterial killing, and emergence of piperacillin resistance. There was logarithmic growth in controls in the initial 24 h, reaching a plateau of similar to 9 log(10) CFU/ml. Bacterial killing following administration of piperacillin via bolus dosing and that after extended infusions were similar. For the lower initial bacterial density, trough total plasma piperacillin concentration/MIC ratios of 3.4 and 10.4 for bolus and extended-infusion regimens, respectively, were able to suppress the emergence of piperacillin resistance. For the higher initial bacterial density, all regimens were associated with progressive growth of a resistant subpopulation. A stratified approach, according to bacterial density, is required to treat patients with nosocomial pneumonia. Antimicrobial monotherapy may be sufficient for some patients. However, for patients with a high bacterial burden, alternative therapeutic strategies are required to maximize bacterial killing and prevent antimicrobial resistance.