Furtado Guilherme Henrique, Cardinal Leandro, Macedo Rodrigo Spineli, Silva Juliana Oliveira, Medeiros Eduardo Alexandrino, Kuti Joseph Levente, Nicolau David Paul
Grupo de Racionalização de Antimicrobianos em Doentes Críticos, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
Rev Soc Bras Med Trop. 2015 Sep-Oct;48(5):539-45. doi: 10.1590/0037-8682-0122-2015.
Monte Carlo simulations have been used for selecting optimal antibiotic regimens for treatment of bacterial infections. The aim of this study was to assess the pharmacokinetic and pharmacodynamic target attainment of intravenous β-lactam regimens commonly used to treat bloodstream infections (BSIs) caused by Gram-negative rod-shaped organisms in a Brazilian teaching hospital.
In total, 5,000 patients were included in the Monte Carlo simulations of distinct antimicrobial regimens to estimate the likelihood of achieving free drug concentrations above the minimum inhibitory concentration (MIC; fT > MIC) for the requisite periods to clear distinct target organisms. Microbiological data were obtained from blood culture isolates harvested in our hospital from 2008 to 2010.
In total, 614 bacterial isolates, including Escherichia coli, Enterobacterspp., Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, were analyzed Piperacillin/tazobactam failed to achieve a cumulative fraction of response (CFR) > 90% for any of the isolates. While standard dosing (short infusion) of β-lactams achieved target attainment for BSIs caused by E. coliand Enterobacterspp., pharmacodynamic target attainment against K. pneumoniaeisolates was only achieved with ceftazidime and meropenem (prolonged infusion). Lastly, only prolonged infusion of high-dose meropenem approached an ideal CFR against P. aeruginosa; however, no antimicrobial regimen achieved an ideal CFR against A. baumannii.
These data reinforce the use of prolonged infusions of high-dose β-lactam antimicrobials as a reasonable strategy for the treatment of BSIs caused by multidrug resistant Gram-negative bacteria in Brazil.
蒙特卡洛模拟已被用于选择治疗细菌感染的最佳抗生素方案。本研究的目的是评估在巴西一家教学医院中，用于治疗由革兰氏阴性杆状菌引起的血流感染（BSIs）的静脉β-内酰胺类方案的药代动力学和药效学目标达成情况。
总共5000名患者被纳入不同抗菌方案的蒙特卡洛模拟，以估计在清除不同目标病原体的必要时间段内，达到高于最低抑菌浓度（MIC；fT > MIC）的游离药物浓度的可能性。微生物学数据来自于2008年至2010年在我院采集的血培养分离株。
总共分析了614株细菌分离株，包括大肠杆菌、肠杆菌属、肺炎克雷伯菌、鲍曼不动杆菌和铜绿假单胞菌。哌拉西林/他唑巴坦对任何分离株均未达到累积反应分数（CFR）> 90%。虽然β-内酰胺类的标准剂量（短时间输注）对由大肠杆菌和肠杆菌属引起的血流感染达到了目标，但仅头孢他啶和美罗培南（长时间输注）对肺炎克雷伯菌分离株实现了药效学目标达成。最后，只有长时间输注高剂量美罗培南接近对铜绿假单胞菌的理想CFR；然而，没有抗菌方案对鲍曼不动杆菌达到理想的CFR。
这些数据支持将长时间输注高剂量β-内酰胺类抗菌药物作为巴西治疗由多重耐药革兰氏阴性菌引起的血流感染的合理策略。
