Daptomycin is widely used for severe Gram-positive infections, yet substantial pharmacokinetic variability and a narrow therapeutic window challenge the adequacy of conventional fixed-dose and weight-based regimens. This paper discusses the rationale for moving from dose-based to exposure-guided dosing. This position paper was informed by a focused, narrative literature search of PubMed, Scopus, and Web of Science, complemented by reference list screening, with emphasis on studies addressing daptomycin pharmacokinetics, toxicity–exposure relationships, dosing strategies, and therapeutic drug monitoring. The reviewed evidence indicates that conventional dosing strategies do not reliably predict systemic exposure and may inadequately account for clinically important variability between patients. Therapeutic drug monitoring emerges as a valuable tool to support more individualized dosing, improve exposure control, and reduce the risk of toxicity. Pragmatic limited-sampling strategies, particularly when combined with Bayesian estimation, may facilitate implementation in clinical practice. In settings where precision dosing is clinically relevant, fixed-dose and weight-based regimens used without subsequent exposure assessment may be insufficient. Exposure-guided dosing supported by therapeutic drug monitoring represents a more robust approach, although the evidence base remains largely observational and pharmacokinetic rather than outcome-driven.
Moreal et al. (Thu,) studied this question.
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