{"title":"因化脓性 AKI 而接受持续肾脏替代疗法的患者中,延长美罗培南疗程与实现积极 PK/PD 之间的关系","authors":"Shinya Chihara, Tomoyuki Ishigo, Satoshi Kazuma, Kana Matsumoto, Kunihiko Morita, Yoshiki Masuda","doi":"10.3390/antibiotics13080755","DOIUrl":null,"url":null,"abstract":"Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. In addition, if the MIC was 1–2 mg/L, the simulation results indicated that aggressive PK/PD can be achieved by continuous infusion at 3 g/24 h without increasing the daily dose.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"11 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association between Extended Meropenem Regimen and Achievement of Aggressive PK/PD in Patients Receiving Continuous Renal Replacement Therapy for Septic AKI\",\"authors\":\"Shinya Chihara, Tomoyuki Ishigo, Satoshi Kazuma, Kana Matsumoto, Kunihiko Morita, Yoshiki Masuda\",\"doi\":\"10.3390/antibiotics13080755\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. 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引用次数: 0
摘要
与保守目标相比,积极的药代动力学(PK)/药效学(PD)目标显示出更好的微生物根除率和更低的耐药菌株产生倾向。我们研究了在因脓毒症急性肾损伤(AKI)而接受持续肾脏替代治疗(CRRT)的患者中,使用每 8 小时输注 1 克、持续 3 小时的美罗培南方案,从疗效和安全性的角度来看,美罗培南的血药浓度(包括积极的 PK/PD)是否可以接受。积极的 PK/PD 目标被定义为游离浓度(%fT)> 4 × 最小抑菌浓度(MIC)的时间百分比,毒性阈值被定义为谷浓度>45 mg/L,并评估了每个 MIC 的达标百分比。MIC 为 0.5 mg/L 的病原体的 100% fT > 4 × MIC 为 89%,MIC 为 2 mg/L 的病原体的 100% fT > 4 × MIC 为 56%。美罗培南的平均稳态谷浓度为 11.9 ± 9.0 mg/L,最大稳态谷浓度为 29.2 mg/L。使用贝叶斯估算法进行的模拟显示,在MIC为2 mg/L的情况下,通过3 g/24小时连续输注给药实现100% fT > 4 × MIC的概率为100%。我们发现,对于因脓毒性AKI接受CRRT治疗的患者来说,在MIC为0.5 mg/L的情况下,采用每8小时输注1 g、持续3小时的美罗培南方案可实现积极的PK/PD。此外,该方案达到毒性范围的风险较低。此外,如果 MIC 为 1-2 mg/L,模拟结果表明,在不增加每日剂量的情况下,以 3 克/24 小时的剂量持续输注可实现积极的 PK/PD。
Association between Extended Meropenem Regimen and Achievement of Aggressive PK/PD in Patients Receiving Continuous Renal Replacement Therapy for Septic AKI
Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. In addition, if the MIC was 1–2 mg/L, the simulation results indicated that aggressive PK/PD can be achieved by continuous infusion at 3 g/24 h without increasing the daily dose.