Beraldi-Magalhaes Francisco, Parker Suzanne L, Sanches Cristina, Garcia Leandro Sousa, Souza Carvalho Brenda Karoline, Costa Amanda Araujo, Fachi Mariana Millan, de Liz Marcus Vinicius, de Souza Alexandra Brito, Safe Izabella Picinin, Pontarolo Roberto, Wallis Steven, Lipman Jeffrey, Roberts Jason A, Cordeiro-Santos Marcelo
Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil.
Trop Med Infect Dis. 2023 Jun 8;8(6):312. doi: 10.3390/tropicalmed8060312.
Patients with tuberculosis (TB) may develop multi-organ failure and require admission to intensive care. In these cases, the mortality rates are as high as 78% and may be caused by suboptimal serum concentrations of first-line TB drugs. This study aims to compare the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide and ethambutol patients in intensive care units (ICU) to outpatients and to evaluate drug serum concentrations as a potential cause of mortality.
A prospective pharmacokinetic (PK) study was performed in Amazonas State, Brazil. The primary PK parameters of outpatients who achieved clinical and microbiological cure were used as a comparative target in a non-compartmental analysis.
Thirteen ICU and twenty outpatients were recruited. The clearance and volume of distribution were lower for rifampin, isoniazid, pyrazinamide and ethambutol. ICU thirty-day mortality was 77% versus a cure rate of 89% in outpatients.
ICU patients had a lower clearance and volume of distribution for rifampin, isoniazid, pyrazinamide and ethambutol compared to the outpatient group. These may reflect changes to organ function, impeded absorption and distribution to the site of infection in ICU patients and have the potential to impact clinical outcomes.
结核病患者可能会出现多器官功能衰竭，需要入住重症监护病房。在这些情况下，死亡率高达78%，可能是由一线抗结核药物血清浓度不理想所致。本研究旨在比较重症监护病房（ICU）患者与门诊患者口服利福平、异烟肼、吡嗪酰胺和乙胺丁醇的药代动力学，并评估药物血清浓度作为死亡的潜在原因。
在巴西亚马孙州进行了一项前瞻性药代动力学（PK）研究。在非房室分析中，将实现临床和微生物学治愈的门诊患者的主要PK参数用作比较目标。
招募了13名ICU患者和20名门诊患者。利福平、异烟肼、吡嗪酰胺和乙胺丁醇的清除率和分布容积较低。ICU患者30天死亡率为77%，而门诊患者的治愈率为89%。
与门诊患者组相比，ICU患者的利福平、异烟肼、吡嗪酰胺和乙胺丁醇清除率和分布容积较低。这些可能反映了ICU患者器官功能的变化、吸收受阻以及感染部位的分布情况，并有可能影响临床结局。
