Neely, Michael N

ABSTRACT Beta‐lactam antibiotics (beta‐lactams) are first‐line treatments for most major infectious syndromes in acutely ill patients, with in vitro activity against common pathogens, demonstrated efficacy in trials, and a perceived low risk of adverse effects. The current dosing approach, informed by population‐level data, tends to be simplistically reduced to a “one size fits all” dosing method which only accounts for body weight (i.e., in pediatrics) and end organ function to estimate drug clearance (e.g., estimated glomerular filtration rate); this approach results in substantial variability in observed serum concentrations in acutely ill patients, which can compromise real‐world effectiveness and safety. Beta‐lactam dose individualization, therefore, defined as a dosing regimen for one patient informed by measured concentrations from that patient, has been recommended in international clinical guidelines. Comprehensive guidance on best practices for beta‐lactam dose individualization is lacking. To address this knowledge gap and develop guidance, a multidisciplinary panel of international experts was assembled from the disciplines of infectious diseases, critical care, pharmacometrics, and laboratory medicine, representing both adults and pediatrics. The panel systematically evaluated the literature, using the GRADE approach where feasible, to address broad thematic questions pertaining to whether beta‐lactam dose individualization should be pursued, for what indications beta‐lactam dose individualization is warranted, and the most critical considerations and best practices for implementation of beta‐lactam individualization. The resultant consensus recommendations will equip healthcare professionals caring for acutely ill patients treated with beta‐lactam therapy with the evidence and tools necessary to guide optimal use of beta‐lactam dose individualization.

Accurate assessment of renal function is fundamental to dosing renally eliminated drugs. For decades, serum creatinine–based estimating equations have been used to approximate glomerular filtration rate (GFR) for this purpose. While these equations perform reasonably well at the population level, they exhibit substantial individual‐level imprecision and inaccuracy. Simultaneously, recent efforts to remove race from estimating equations addressed important ethical concerns but did not resolve the core limitation of population‐based estimation for individual drug dosing. In this perspective, we argue that personalized dosing requires a shift away from demographic surrogates toward direct measurement of renal clearance and clarify when incremental therapeutic complexity is warranted. We review the limitations of endogenous biomarkers, discuss the role of cystatin C, and propose exogenously measured GFR using iohexol integrated within a Bayesian pharmacometric framework as a clinically actionable approach to individualized drug dosing. Practically, this framework can be implemented by administering a small iohexol dose, collecting sparse timed samples, estimating absolute mGFR and its uncertainty with Bayesian software, and using that posterior estimate to refine renal dose selection.