Advertisement

How to Treat Sepsis in the Background of Resistance?: Role of Pharmacodynamics / Pharmacokinetics in Treating Sepsis

  • Mohit Agrawal
  • Ashok RattanEmail author
Review Article
  • 25 Downloads

Abstract

Though a decline has been seen in child mortality and morbidity over the last decades, sepsis in neonates and infants remains a major cause of death. Optimal use of antibiotics in sepsis management is a key factor which can further reduce the number of poor clinical outcomes. Selecting the right antibiotic to which the offending bacteria is susceptible and administrating the antibiotic within the first hour can save many lives. However, the pharmacokinetic profile of an antibiotic is affected by developmental changes such as capacity of drug metabolizing enzymes and maturation of organ function. This can affect antibiotic exposure and response in neonates and infants. While suspecting sepsis, the primary focus of empiric treatment during the initial phase is to assure efficacy and it must be broad based to cover all suspected pathogens. Once the bacterial etiology is confirmed as a cause of sepsis and the in vitro antibiotic susceptibility is established, targeted treatment can be started which ensures optimal balance between efficacy and safety.

Keywords

Concentration dependent killing Minimum inhibitory concentration Pediatric sepsis Pharmacodynamic Pharmacokinetic Time dependent killing 

Notes

Authors’ Contribution

Both the authors have contributed equally for the manuscript. AR is the guarantor for this paper.

Compliance with Ethical Standards

Conflict of Interest

None.

References

  1. 1.
    Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26:1–10.CrossRefGoogle Scholar
  2. 2.
    McDonald PJ, Craig WA, Kunin CM. Persistent effect of antibiotics on Staphylococcus aureus after exposure for limited periods of time. J Infect Dis. 1977;135:217–23.CrossRefGoogle Scholar
  3. 3.
    Odenholt-Tornqvist I, Löwdin E, Cars O. Postantibiotic sub-MIC effects of vancomycin, roxithromycin, sparfloxacin and amikacin. Antimicrob Agents Chemother. 1992;36:1852–8.CrossRefGoogle Scholar
  4. 4.
    Vogelman B, Craig WA. Kinetics of antimicrobial activity. J Pediatr. 1986;108:835–40.CrossRefGoogle Scholar
  5. 5.
    Craig WA, Ebert SC. Killing and regrowth of bacteria in vitro: a review. Scand J Infect Dis Suppl. 1990;74:63–70.PubMedGoogle Scholar
  6. 6.
    Shah PM, Junghanns W, Stille W. Dosis-Wirkungs-Beziehung der Bakterizidie bei E. coli, K. pneumoniae und Staphylococcus aureus. Dtsch Med Wochenschr. 1976;101:325–8.CrossRefGoogle Scholar
  7. 7.
    Craig WA. Postantibiotic effects and the dosing of macrolides, azalides, and streptogramins. In: Zinner SH, Young LS, Acar JF, Neu HC, editors. Expanding Indications for the New Macrolides, Azalides, and Streptogramins. New York: Marcel Dekker; 1997. p. 27–38.Google Scholar
  8. 8.
    Onufrak NJ, Forrest A, Gonzalez D. Pharmacokinetic and pharmacodynamic principles of anti-infective dosing. Clin Ther. 2016;38:1930–47.CrossRefGoogle Scholar
  9. 9.
    Barger A, Fuhst C, Wiedemann B. Pharmacological indices in antibiotic therapy. J Antimicrob Chemother. 2003;52:893–8.CrossRefGoogle Scholar
  10. 10.
    Le J, Bradley JS. Optimizing antibiotic drug therapy in pediatrics: current state and future needs. J Clin Pharmacol. 2018;58:S108–22.CrossRefGoogle Scholar
  11. 11.
    Downes KJ, Hahn A, Wiles J, Courter JD, Vinks AA. Dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics. Int J Antimicrob Agents. 2014;43:223–30.CrossRefGoogle Scholar
  12. 12.
    Bradley JS, Garonzik SM, Forrest A, Bhavnani SM. Pharmacokinetics, pharmacodynamics, and Monte Carlo simulation: selecting the best antimicrobial dose to treat an infection. Pediatr Infect Dis J. 2010;29:1043–6.CrossRefGoogle Scholar
  13. 13.
    Anderson BJ, Holford NH. Understanding dosing: children are small adults, neonates are immature children. Arch Dis Child. 2013;98:737–44.CrossRefGoogle Scholar
  14. 14.
    Anderson BJ, Holford NH. Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol. 2008;48:303–32.CrossRefGoogle Scholar
  15. 15.
    Mahmood I. Prediction of drug clearance in children: impact of allometric exponents, body weight, and age. Ther Drug Monit. 2007;29:271–8.CrossRefGoogle Scholar
  16. 16.
    Pai VB, Nahata MC. Dosing in pediatric patients. In: Murphy JE, editor. Clinical Pharmacokinetics, 6th ed. Bethesda: American Society of Health-System Pharmacists; 2017. p. 65–76.Google Scholar
  17. 17.
    Nielsen EI, Sandstrom M, Honore PH, Ewald U, Friberg LE. Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modelling of a prospective study. Clin Pharmacokinet. 2009;48:253–63.CrossRefGoogle Scholar
  18. 18.
    Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology–drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349:1157–67.CrossRefGoogle Scholar
  19. 19.
    van den Anker JN, Schwab M, Kearns GL. Developmental pharmacokinetics. Handb Exp Pharmacol. 2011;205:51–75.CrossRefGoogle Scholar
  20. 20.
    Rhodin MM, Anderson BJ, Peters AM, et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol. 2009;24:67–76.CrossRefGoogle Scholar
  21. 21.
    Vinita BP, Nahata MC. Drug dosing in pediatric patients. In: Murphy JE, editor. Clinical Pharmacokinetics, 5th ed. Bethesda: American Society of Health-System Pharmacists; 2012.Google Scholar
  22. 22.
    van Donge T, Bielicki JA, van den Anker J, Pfister M. Key components for antibiotic dose optimization of sepsis in neonates and infants. Front Pediatr. 2018;6:325.CrossRefGoogle Scholar
  23. 23.
    van Donge T, Pfister M, Bielicki J, et al. Quantitative analysis of gentamicin exposure in neonates and infants calls into question its current dosing recommendations. Antimicrob Agents Chemother. 2018;62:02004–17.Google Scholar
  24. 24.
    Sinkeler FS, de Haan TR, Hodiamont CJ, Bijleveld YA, Pajkrt D, Mathôt RAA. Inadequate vancomycin therapy in term and preterm neonates: a retrospective analysis of trough serum concentrations in relation to minimal inhibitory concentrations. BMC Pediatr. 2014;14:193.CrossRefGoogle Scholar
  25. 25.
    Kawasaki T. Update on pediatric sepsis: a review. J Intensive Care. 2017;5:47.CrossRefGoogle Scholar
  26. 26.
    Barker CIS, Standing JF, Kelly LE, et al. Pharmacokinetic studies in children: recommendations for practice and research. Arch Dis Child. 2018;103:695–702.PubMedPubMedCentralGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2020

Authors and Affiliations

  1. 1.Department of MicrobiologyMahatma Gandhi Medical CollegeJaipurIndia
  2. 2.Pathkind LabsGurgaonIndia

Personalised recommendations