Scholarlink

Introduction <p>Daily intravenous dosing of cefepime, meropenem and ceftazidime/avibactam is recommended in patients receiving intermittent hemodialysis (IHD), but requires hospitalization or frequent clinic visits. High dose post-HD administration may offer a more convenient outpatient alternative, but supporting data is limited.</p> Aim <p>To evaluate the feasibility by assessing predicted pharmacokinetic/pharmacodynamic (PK/PD) target attainment and neurotoxicity risk of high-dose post-HD versus daily dosing strategies for cefepime, meropenem, and ceftazidime/avibactam in patients receiving thrice-weekly IHD, using the Monte Carlo simulation (MCS) techniques.</p> Method <p>One-compartment pharmacokinetic models were developed using published data to simulate drug exposure in anuric patients receiving 4-h IHD thrice-weekly. MCS (Crystal Ball, Oracle) assessed the probability of target attainment (PTA) and neurotoxicity risk of various post-HD and daily dosing regimens in 5,000 virtual cohorts for one week. The PK/PD targets were ≥ 60% <i>f</i>T &gt; MIC for cefepime, ≥ 40% <i>f</i>T &gt; MIC for meropenem and ≥ 50% <i>f</i>T &gt; MIC for ceftazidime with ≥ 50% fT &gt; 1&#xa0;g/mL for avibactam, assuming <i>Pseudomonas aeruginosa</i> or <i>Enterobactarales</i> infections. A PTA ≥ 90% was considered optimal for PK/PD target attainment. Safety was also assessed using the neurotoxicity thresholds.</p> Results <p>All daily regimens achieved PTA ≥ 90% on all simulated days. High-dose post-HD cefepime (1–2&#xa0;g) and meropenem (2&#xa0;g) maintained acceptable PTA over 2-day interdialytic periods, but failed to sustain targets through the 3-day period. Ceftazidime/avibactam post-HD dosing (0.94&#xa0;g–0.94&#xa0;g–2.5&#xa0;g) maintained ≥ 90% PTA for ceftazidime throughout the week, though avibactam fell slightly below target on the final day. Predicted neurotoxicity risk was negligible for meropenem and ceftazidime/avibactam, but elevated with higher cefepime doses (1–2&#xa0;g post-HD and 1&#xa0;g daily). Cefepime 0.5&#xa0;g daily, meropenem 0.25–1&#xa0;g daily, and ceftazidime/avibactam 0.94&#xa0;g daily or 0.94&#xa0;g–0.94&#xa0;g–2.5&#xa0;g post-HD attained both PK/PD targets and safety targets.</p> Conclusion <p>High-dose post-HD dosing appears feasible for ceftazidime/avibactam but may be inadequate for cefepime and meropenem over a 3-day interdialytic period. Elevated neurotoxicity risk predicted with higher cefepime doses highlights the importance of cautious dosing and consideration of therapeutic drug monitoring.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Evaluation of high dose post-dialytic versus daily beta-lactam dosing in hemodialysis patients using Monte Carlo simulation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月26日

查看全文
  • Andrew J. Bauman,
  • Olivia G. Caiazza,
  • Nerissa Wan,
  • Sydnee Payer,
  • Olivia G. Pauly,
  • Sierra Shoemaker,
  • Susan J. Lewis

摘要

Introduction

Daily intravenous dosing of cefepime, meropenem and ceftazidime/avibactam is recommended in patients receiving intermittent hemodialysis (IHD), but requires hospitalization or frequent clinic visits. High dose post-HD administration may offer a more convenient outpatient alternative, but supporting data is limited.

Aim

To evaluate the feasibility by assessing predicted pharmacokinetic/pharmacodynamic (PK/PD) target attainment and neurotoxicity risk of high-dose post-HD versus daily dosing strategies for cefepime, meropenem, and ceftazidime/avibactam in patients receiving thrice-weekly IHD, using the Monte Carlo simulation (MCS) techniques.

Method

One-compartment pharmacokinetic models were developed using published data to simulate drug exposure in anuric patients receiving 4-h IHD thrice-weekly. MCS (Crystal Ball, Oracle) assessed the probability of target attainment (PTA) and neurotoxicity risk of various post-HD and daily dosing regimens in 5,000 virtual cohorts for one week. The PK/PD targets were ≥ 60% fT > MIC for cefepime, ≥ 40% fT > MIC for meropenem and ≥ 50% fT > MIC for ceftazidime with ≥ 50% fT > 1 g/mL for avibactam, assuming Pseudomonas aeruginosa or Enterobactarales infections. A PTA ≥ 90% was considered optimal for PK/PD target attainment. Safety was also assessed using the neurotoxicity thresholds.

Results

All daily regimens achieved PTA ≥ 90% on all simulated days. High-dose post-HD cefepime (1–2 g) and meropenem (2 g) maintained acceptable PTA over 2-day interdialytic periods, but failed to sustain targets through the 3-day period. Ceftazidime/avibactam post-HD dosing (0.94 g–0.94 g–2.5 g) maintained ≥ 90% PTA for ceftazidime throughout the week, though avibactam fell slightly below target on the final day. Predicted neurotoxicity risk was negligible for meropenem and ceftazidime/avibactam, but elevated with higher cefepime doses (1–2 g post-HD and 1 g daily). Cefepime 0.5 g daily, meropenem 0.25–1 g daily, and ceftazidime/avibactam 0.94 g daily or 0.94 g–0.94 g–2.5 g post-HD attained both PK/PD targets and safety targets.

Conclusion

High-dose post-HD dosing appears feasible for ceftazidime/avibactam but may be inadequate for cefepime and meropenem over a 3-day interdialytic period. Elevated neurotoxicity risk predicted with higher cefepime doses highlights the importance of cautious dosing and consideration of therapeutic drug monitoring.