蒙特卡罗模拟评估头孢他啶/阿维巴坦在 和 血流感染中的应用。
Evaluation of Ceftazidime/Avibactam Administration in and Bloodstream Infections by Monte Carlo Simulation.
机构信息
Department of Laboratory, First Affiliated Hospital of University of Science and Technology of China, Hefei, People's Republic of China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University, Hangzhou, People's Republic of China.
出版信息
Drug Des Devel Ther. 2021 Jul 6;15:2899-2905. doi: 10.2147/DDDT.S309825. eCollection 2021.
PURPOSE
To evaluate the administration regimen of ceftazidime/avibactam (CZA) for bloodstream infections caused by and .
METHODS
The minimal inhibitory concentrations (MICs) of CZA against and isolated from blood cultures at member hospitals in BRICS (Blood Bacterial Resistant Investigation Collaborative System) in 2019 were determined by broth micro-dilution methodology. A 10,000-patient Monte Carlo simulation (MCS) was used to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) for different CZA dosage regimens to evaluate their efficacies and optimize the best initial dosage regimen.
RESULTS
Altogether, 6487 and strains were isolated from the blood cultures. The overall CZA resistance rate was 2.31%, of which the and rates were 1.57% and 14.29%, respectively. The MCS showed that the greater the MIC value, the worse the therapeutic effect. When the CZA MIC was ≤8 mg/L, the standard dose (2.5g iv q8h) achieved 90% PTA in the subset of patients with creatinine clearance (CrCl) values from 51 to 120 mL/min. Although the high-dose regimen (3.75g iv q8h) achieved 90% PTA in patients with CrCl values from 121 to 190 mL/min, implementing the low-dose regimen (1.25g iv q8h) was also effective for patients in the 51-89 mL/min CrCl range. Generally, the high-dose regimen (3.75g iv q8h) reached 90% CFR against all of the strains. Conversely, in patients with CrCl values of 121-190 mL/min, the standard dose (2.5g iv q8h) failed to reach 90% CFR against some members and . When the dose was reduced to the low-dose regimen (1.25g iv q8h), no patients reached 90% CFR against some members and
CONCLUSION
CZA has good antibacterial activity against and in bloodstream infections. Clinicians could make individualized treatment regimens in accordance with the sensitivity of the strains and the level of renal function in their patients to best predict the drug-related clinical responses.
目的
评估头孢他啶/阿维巴坦（CZA）治疗血流感染的给药方案，这些感染由 和 引起。
方法
2019 年，金砖国家（Blood Bacterial Resistant Investigation Collaborative System，BRICS）成员医院的血培养中分离出的 和 菌株，采用肉汤微量稀释法测定头孢他啶/阿维巴坦的最小抑菌浓度（MIC）。采用 10000 例蒙特卡罗模拟（MCS）计算不同头孢他啶/阿维巴坦剂量方案的目标达成率（PTA）和累积反应分数（CFR），以评估其疗效并优化最佳初始剂量方案。
结果
共从血培养物中分离出 6487 株 和 菌株。总体而言，CZA 的耐药率为 2.31%，其中 和 的耐药率分别为 1.57%和 14.29%。MCS 显示，MIC 值越大，治疗效果越差。当 CZA MIC 值≤8mg/L 时，标准剂量（2.5g iv q8h）在肌酐清除率（CrCl）值为 51-120ml/min 的患者亚组中达到 90%的 PTA。虽然高剂量方案（3.75g iv q8h）在 CrCl 值为 121-190ml/min 的患者中达到 90%的 PTA，但在 CrCl 值为 51-89ml/min 的患者中采用低剂量方案（1.25g iv q8h）也同样有效。一般来说，高剂量方案（3.75g iv q8h）对所有菌株均达到 90%的 CFR。相反，在 CrCl 值为 121-190ml/min 的患者中，标准剂量（2.5g iv q8h）对某些 成员和 的 CFR 无法达到 90%。当剂量降低至低剂量方案（1.25g iv q8h）时，某些 成员和 没有患者达到 90%的 CFR。
结论
头孢他啶/阿维巴坦对血流感染中的 和 具有良好的抗菌活性。临床医生可以根据菌株的敏感性和患者的肾功能水平制定个体化的治疗方案，以最佳预测与药物相关的临床反应。
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