a Department of Respiratory and Critical Care Medicine , Peking University People's Hospital , Beijing , China.
b Department of Respiratory Diseases , Chinese PLA General Hospital , Beijing , China.
Infect Dis (Lond). 2018 Jul;50(7):507-513. doi: 10.1080/23744235.2018.1423703. Epub 2018 Jan 9.
Pneumonia caused by carbapenemase-producing Klebsiella pneumoniae (CP-KP) are increasingly encountered in hospitals worldwide, causing high mortality due to lack of treatment options. The goal of this study was to assess the efficacy of tigecycline and minocycline for CP-KP hospital-acquired pneumonia (HAP) by using Monte Carlo simulation.
A total of 164 non-duplicated CP-KP strains were collected from sputum or blood in patients with HAP. The MICs for antimicrobials were determined by the agar dilution method. A 10,000-patient Monte Carlo Simulation based on a PK/PD model incorporating the MICs and population pharmacokinetic parameters were conducted to calculate probability of target attainment (PTA) at each MIC value and total cumulative fraction of response (CFR).
The susceptibility rate of tigecycline and minocycline were 79.9% and 41.5%, respectively. At recommended doses, an optimal PTA of 90% was obtained for treating HAP caused by CP-KP with MICs of tigecycline ≤0.5 mg/L or minocycline ≤4 mg/L. The CFR of tigecycline at the recommended dose and double dose (100 mg q12h) were 71.2% and 90.2%, respectively. The CFR of minocycline at recommended dose and double dose (200 mg q12h) was 53.4% and 77.2%, respectively.
The findings of this study suggest that the recommended dose of tigecycline was not effective in HAP caused by CP-KP, and a higher CFR indicating a better clinical efficacy can be gained by doubling the dose (100 mg q12h). minocycline (200 mg q12h) might be a potential alternative of tigecycline to against strains with MICs ≤ 8 mg/L.
产碳青霉烯酶肺炎克雷伯菌（CP-KP）引起的肺炎在全球医院中越来越常见，由于缺乏治疗选择，死亡率很高。本研究旨在通过蒙特卡罗模拟评估替加环素和米诺环素治疗 CP-KP 医院获得性肺炎（HAP）的疗效。
从 HAP 患者的痰或血液中收集了 164 株非重复 CP-KP 株。通过琼脂稀释法测定抗菌药物的 MIC。基于包含 MIC 和群体药代动力学参数的 PK/PD 模型，进行了 10000 例患者的蒙特卡罗模拟，以计算每个 MIC 值和总累积反应分数（CFR）的目标达标率（PTA）。
替加环素和米诺环素的敏感性率分别为 79.9%和 41.5%。在推荐剂量下，对于 MIC 值为替加环素≤0.5mg/L 或米诺环素≤4mg/L 的 CP-KP 引起的 HAP，获得了 90%的最佳 PTA。替加环素在推荐剂量和双剂量（100mg q12h）下的 CFR 分别为 71.2%和 90.2%。米诺环素在推荐剂量和双剂量（200mg q12h）下的 CFR 分别为 53.4%和 77.2%。
本研究结果表明，替加环素的推荐剂量对 CP-KP 引起的 HAP 无效，通过加倍剂量（100mg q12h）可获得更高的 CFR，表明临床疗效更好。米诺环素（200mg q12h）可能是替加环素对抗 MICs≤8mg/L 菌株的潜在替代药物。
