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

Posted on by Jacqueline Hannam

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.

References:

  1. Bray C, Bell LN, Liang H, Haykal R, Kaiksow F, Mazza JJ, et al. Erythrocyte Sedimentation Rate and C-reactive Protein Measurements and Their Relevance in Clinical Medicine. WMJ : official publication of the State Medical Society of Wisconsin. 2016;115(6):317-21.
  2. Taylor R, Jones A, Kelly S, Simpson M, Mabey J. A Review of the Value of Procalcitonin as a Marker of Infection. Cureus. 2017;9(4):e1148.
  3. Lapillonne A, Basson E, Monneret G, Bienvenu J, Salle BL. Lack of specificity of procalcitonin for sepsis diagnosis in premature infants. Lancet (London, England). 1998;351(9110):1211-2.
  4. Lautz AJ, Dziorny AC, Denson AR, O’Connor KA, Chilutti MR, Ross RK, et al. Value of Procalcitonin Measurement for Early Evidence of Severe Bacterial Infections in the Pediatric Intensive Care Unit. The Journal of Pediatrics. 2016;179:74-81.e2.
  5. Lee J, Bang YH, Lee EH, Choi BM, Hong YS. The influencing factors on procalcitonin values in newborns with noninfectious conditions during the first week of life. Korean Journal of Pediatrics. 2017;60(1):10-6.
  6. Hahn WH, Song JH, Park IS, Kim H, Park S, Oh MH. Reference Intervals of Serum Procalcitonin Are Affected by Postnatal Age in Very Low Birth Weight Infants during the First 60 Days after Birth. Neonatology. 2015;108(1):60-4.
  7. Fukuzumi N, Osawa K, Sato I, Iwatani S, Ishino R, Hayashi N, et al. Age-specific percentile-based reference curve of serum procalcitonin concentrations in Japanese preterm infants. Scientific reports. 2016;6:23871.
  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.
  9. Turner D, Hammerman C, Rudensky B, Schlesinger Y, Goia C, Schimmel MS. Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram. Archives of disease in childhood Fetal and neonatal edition. 2006;91(4):F283-6.
2019