Therapeutic drug monitoring and the role of pharmacokinetics/pharmacodynamics in optimizing beta-lactam antibiotic dosing for deep-seated infections: a systematic review
Vale, Cassandra, Sime, Fekade B., Cotta, Menino O., Eriksson, Lars, Roberts, Jason A, Horvath, Robert, and Abdul-Aziz, Mohd H. (2026)
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.
