Yu-Ju Tseng, Chih-Hsun Tai, Guan-Yuan Chen, Yen-Lin Chen, Shih-Chi Ku, Tsung-Yu Pai, Chien-Chih Wu
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These changes complicate β-lactam antibiotic dosing, potentially resulting in suboptimal efficacy or increased toxicity.</p><p><strong>Objectives: </strong>To evaluate the attainment of PK/pharmacodynamic (PD) targets, the prevalence of subtherapeutic and supratherapeutic concentrations, and the incidence of neurotoxicity among LBW patients treated with piperacillin/tazobactam (TZP), cefepime (FEP), and meropenem (MEM).</p><p><strong>Design: </strong>A prospective observational study conducted at a tertiary hospital from January 2020 to December 2022.</p><p><strong>Methods: </strong>Adult patients with a body mass index ⩽18.5 kg/m<sup>2</sup> who received TZP, FEP, or MEM were included. Trough serum concentrations were analyzed for PK/PD targets: 100% time above minimum inhibitory concentration (100% fT > MIC) and 100% time above four times MIC (100% fT > 4MIC). Neurotoxicity was assessed using standardized criteria. Statistical analyses identified factors associated with concentration variability and adverse outcomes.</p><p><strong>Results: </strong>Seventy-two patients were included: 29 received TZP, 23 FEP, and 20 MEM. Achievement of the 100% fT > MIC target was comparable across all antibiotics (~70%), but 100% fT > 4 MIC attainment was significantly higher for FEP (47.8%) than for TZP (10.3%) and MEM (30%) (<i>p</i> = 0.01). Supratherapeutic concentrations were observed in 34.8% of FEP users compared to 3.4% and 5% for TZP and MEM, respectively (<i>p</i> = 0.002). Neurotoxicity occurred in 13% of FEP patients but was not reported in TZP or MEM groups (<i>p</i> = 0.04). Subtherapeutic concentrations were noted in approximately 30% of patients across all groups.</p><p><strong>Conclusion: </strong>PK changes complicate β-lactam antibiotic dosing, resulting in frequent failure to achieve PK/PD targets. FEP demonstrated a particularly high risk of supratherapeutic concentrations and neurotoxicity. Therapeutic drug monitoring is crucial to optimize dosing and improve safety in this population.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251320414"},"PeriodicalIF":3.4000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837059/pdf/","citationCount":"0","resultStr":"{\"title\":\"Navigating pharmacokinetic and pharmacodynamics challenges of β-lactam antibiotics in patients with low body weight: efficacy, toxicity, and dosage optimization.\",\"authors\":\"Yu-Ju Tseng, Chih-Hsun Tai, Guan-Yuan Chen, Yen-Lin Chen, Shih-Chi Ku, Tsung-Yu Pai, Chien-Chih Wu\",\"doi\":\"10.1177/20420986251320414\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Patients with low body weight (LBW) often exhibit altered pharmacokinetics (PK) in renal clearance and total body water. These changes complicate β-lactam antibiotic dosing, potentially resulting in suboptimal efficacy or increased toxicity.</p><p><strong>Objectives: </strong>To evaluate the attainment of PK/pharmacodynamic (PD) targets, the prevalence of subtherapeutic and supratherapeutic concentrations, and the incidence of neurotoxicity among LBW patients treated with piperacillin/tazobactam (TZP), cefepime (FEP), and meropenem (MEM).</p><p><strong>Design: </strong>A prospective observational study conducted at a tertiary hospital from January 2020 to December 2022.</p><p><strong>Methods: </strong>Adult patients with a body mass index ⩽18.5 kg/m<sup>2</sup> who received TZP, FEP, or MEM were included. Trough serum concentrations were analyzed for PK/PD targets: 100% time above minimum inhibitory concentration (100% fT > MIC) and 100% time above four times MIC (100% fT > 4MIC). Neurotoxicity was assessed using standardized criteria. Statistical analyses identified factors associated with concentration variability and adverse outcomes.</p><p><strong>Results: </strong>Seventy-two patients were included: 29 received TZP, 23 FEP, and 20 MEM. Achievement of the 100% fT > MIC target was comparable across all antibiotics (~70%), but 100% fT > 4 MIC attainment was significantly higher for FEP (47.8%) than for TZP (10.3%) and MEM (30%) (<i>p</i> = 0.01). Supratherapeutic concentrations were observed in 34.8% of FEP users compared to 3.4% and 5% for TZP and MEM, respectively (<i>p</i> = 0.002). Neurotoxicity occurred in 13% of FEP patients but was not reported in TZP or MEM groups (<i>p</i> = 0.04). Subtherapeutic concentrations were noted in approximately 30% of patients across all groups.</p><p><strong>Conclusion: </strong>PK changes complicate β-lactam antibiotic dosing, resulting in frequent failure to achieve PK/PD targets. FEP demonstrated a particularly high risk of supratherapeutic concentrations and neurotoxicity. 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引用次数: 0
摘要
背景：低体重（LBW）患者经常表现出肾脏清除率和全身水分的药代动力学（PK）改变。这些变化使β-内酰胺抗生素的剂量复杂化，可能导致次优疗效或毒性增加。目的：评价哌拉西林/他唑巴坦（TZP）、头孢吡肟（FEP）、美罗培南（MEM）治疗的LBW患者PK/药效学（PD）指标的实现情况、亚治疗浓度和超治疗浓度的发生率以及神经毒性的发生率。设计：2020年1月至2022年12月在某三级医院进行前瞻性观察性研究。方法：纳入接受TZP、FEP或MEM治疗的体重指数≥18.5 kg/m2的成年患者。谷血清浓度分析PK/PD目标：100%时间高于最低抑制浓度（100% fT > MIC）和100%时间高于4倍MIC （100% fT > 4MIC）。采用标准化标准评估神经毒性。统计分析确定了与浓度变异性和不良结果相关的因素。结果：纳入72例患者：29例采用TZP， 23例采用FEP， 20例采用MEM。所有抗生素的100% fT b> MIC目标达到率相当（~70%），但FEP的100% fT bbbb4 MIC达到率（47.8%）显著高于TZP（10.3%）和MEM (30%) （p = 0.01）。在34.8%的FEP使用者中观察到超治疗浓度，而TZP和MEM分别为3.4%和5% （p = 0.002）。13%的FEP患者发生神经毒性，而TZP或MEM组未报告神经毒性（p = 0.04）。在所有组中约30%的患者中发现亚治疗浓度。结论：药代动力学变化使β-内酰胺类抗生素给药复杂化，经常导致药代动力学/药代动力学指标无法达到。FEP表现出特别高的超治疗浓度和神经毒性风险。治疗药物监测对于优化该人群的剂量和提高安全性至关重要。
Navigating pharmacokinetic and pharmacodynamics challenges of β-lactam antibiotics in patients with low body weight: efficacy, toxicity, and dosage optimization.
Background: Patients with low body weight (LBW) often exhibit altered pharmacokinetics (PK) in renal clearance and total body water. These changes complicate β-lactam antibiotic dosing, potentially resulting in suboptimal efficacy or increased toxicity.
Objectives: To evaluate the attainment of PK/pharmacodynamic (PD) targets, the prevalence of subtherapeutic and supratherapeutic concentrations, and the incidence of neurotoxicity among LBW patients treated with piperacillin/tazobactam (TZP), cefepime (FEP), and meropenem (MEM).
Design: A prospective observational study conducted at a tertiary hospital from January 2020 to December 2022.
Methods: Adult patients with a body mass index ⩽18.5 kg/m2 who received TZP, FEP, or MEM were included. Trough serum concentrations were analyzed for PK/PD targets: 100% time above minimum inhibitory concentration (100% fT > MIC) and 100% time above four times MIC (100% fT > 4MIC). Neurotoxicity was assessed using standardized criteria. Statistical analyses identified factors associated with concentration variability and adverse outcomes.
Results: Seventy-two patients were included: 29 received TZP, 23 FEP, and 20 MEM. Achievement of the 100% fT > MIC target was comparable across all antibiotics (~70%), but 100% fT > 4 MIC attainment was significantly higher for FEP (47.8%) than for TZP (10.3%) and MEM (30%) (p = 0.01). Supratherapeutic concentrations were observed in 34.8% of FEP users compared to 3.4% and 5% for TZP and MEM, respectively (p = 0.002). Neurotoxicity occurred in 13% of FEP patients but was not reported in TZP or MEM groups (p = 0.04). Subtherapeutic concentrations were noted in approximately 30% of patients across all groups.
Conclusion: PK changes complicate β-lactam antibiotic dosing, resulting in frequent failure to achieve PK/PD targets. FEP demonstrated a particularly high risk of supratherapeutic concentrations and neurotoxicity. Therapeutic drug monitoring is crucial to optimize dosing and improve safety in this population.
期刊介绍：
Therapeutic Advances in Drug Safety delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies pertaining to the safe use of drugs in patients.
The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in drug safety, providing a forum in print and online for publishing the highest quality articles in this area. The editors welcome articles of current interest on research across all areas of drug safety, including therapeutic drug monitoring, pharmacoepidemiology, adverse drug reactions, drug interactions, pharmacokinetics, pharmacovigilance, medication/prescribing errors, risk management, ethics and regulation.
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