Therapeutic drug monitoring and the role of pharmacokinetics/pharmacodynamics in optimizing beta-lactam antibiotic dosing for deep-seated infections: a systematic review

BACKGROUND: Therapeutic drug monitoring (TDM) may help optimize beta-lactam antibiotic dosing in patients with deep-seated infections. However, its impact on clinical outcomes remains unclear. OBJECTIVE: The objective of this review was to evaluate the existing evidence on the role of TDM and pharmacokinetic/pharmacodynamic (PK/PD)-guided optimization of beta-lactam antibiotic dosing in achieving PK/PD targets, and improving clinical outcomes in patients with deep-seated infections. METHODS: We conducted a systematic review of studies reporting on beta-lactam TDM, PK/PD target attainment, and clinical outcomes in adult (≥18 years) patients with confirmed deep-seated infections, including complex bacteraemias with a suspected or proven deep-seated source, infective endocarditis, bone and joint infection, and epidural abscess. The search was conducted using MEDLINE (via PubMed), Embase, CINAHL and CENTRAL from inception to June 2025. RESULTS: Twelve studies were included in the final analysis. Considerable variability was observed in PK/PD target definitions and attainment, dosing adjustments and outcome reporting. Eleven of the twelve studies were rated as poor quality on the Newcastle-Ottawa Scale due to lack of comparability. Only one study included a non-TDM comparator group and the authors reported no significant difference in clinical outcomes. Three studies showed a trend towards improved clinical outcomes with TDM-guided dosing. TDM frequently led to dose reductions due to concerns of beta-lactam antibiotic toxicity with standard dosing. CONCLUSION: Current evidence supporting beta-lactam antibiotic TDM in deep-seated infections is limited by methodological heterogeneity and poor study quality. Well-designed trials are needed to establish the clinical utility of TDM in this setting.