Navigating pharmacokinetic and pharmacodynamics challenges of β-lactam antibiotics in patients with low body weight: efficacy, toxicity, and dosage optimization.

Abstract

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.