Future work in Auckland: procalcitonin in healthy and infected neonates to inform PKPD disease progression modelling

Appropriate antimicrobial therapy in neonates and babies is complicated by pharmacokinetic (PK) changes with age, body size and disease. Additionally we lack pharmacodynamic (PD) measures to gauge patient response. A correlation exists between elevated concentrations of procalcitonin (PCT) and infection +/- sepsis butmultiple other factors also contribute to PCT fluctuations (1, 2). For example, PCT concentrations are altered with trauma, surgery, burns, acute kidney injury, respiratory distress syndrome, haemodynamic failure, factors relating to birth including preterm delivery, maternal chorioamnionitis, low APGAR score at delivery, low birth weight and others (3-7). A normal time course of PCT elevation followed by return to baseline concentrations has been shown to occur in healthy neonates over the 48 h following birth (8, 9), and this differs in low birth weight infants (6). Consequently, the time course of PCT in neonates is complex, measurements are unsurprisingly variable and they can be difficult to interpret in the context of multiple patient factors.

Current dosing regimens for antibiotics are empirical with little integration of PK or PD knowledge, based instead on exceeding a minimum inhibitory concentration determined in laboratory cultures incubated for 48-72 h with drug concentrations selected at 2 fold increments. PCT measurements may provide a useful surrogate marker of drug response during infection that can be incorporated into these models to describe the time course of both infection and infection resolution with antibiotic therapy. Future work at Auckland will focus on establishing a dataset for PCT concentrations in healthy and infected neonates, as well as adults, from prospective data collection and collaboration with other centres, for the purposes of disease progression modelling and antibiotic therapy.


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  8. Claudio C, Alessandra P, Naila R, Stegagno M, Maria De G, Osborn JF, et al. Reliability of Procalcitonin Concentrations for the Diagnosis of Sepsis in Critically Ill Neonates. Clinical Infectious Diseases. 1998;26(3):664-72.
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Jacqueline Hannam