Skip to main content

Advertisement

SpringerLink
Log in

Serum concentrations of amoxicillin in neonates during continuous intravenous infusion

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Amoxicillin is commonly used for the treatment of neonatal bacterial infection with intermittent dosing (ID) regimens. However, increasing bacterial resistance, in addition to a lack of new antimicrobial agents, urges the optimization of current therapeutic options. Clinical studies in adults suggest continuous infusion (CI) regimens of beta-lactam antibiotics to be superior to ID. There are as yet no guidelines concerning the CI dosing of amoxicillin. The present study was developed to describe the CI pharmacokinetics and -dynamics of amoxicillin during the first 3 days of life in search of the optimal dosing regimen. Neonates with a gestational age above 34 weeks, at risk of neonatal infection and requiring amoxicillin therapy, were included. Serum concentrations of amoxicillin were measured during CI on days 1 and 3 in the steady state. Twenty-two serum samples of 11 patients were collected. All patients reached and retained serum concentrations of amoxicillin within the therapeutic range without exceeding the toxic concentration (serum concentrations on day 1 mean 55.4 mg/l, range 30.9–69.5, SD 10.5, and on day 3 48.8 mg/l, range 25.5–92.4, SD 18.4). There was no significant decrease in concentration from day 1 to day 3 (p = 0.38). This study showed therapeutic, nontoxic concentrations of amoxicillin in neonates on CI of amoxicillin in the first 3 days of life. Randomized controlled trials should reveal whether the clinical benefits of the CI of amoxicillin exceed those of ID regimens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Mouton JW, Vinks AA (2009) Continuous infusion of beta-lactams. Curr Opin Crit Care 13:598–606

    Article  Google Scholar 

  2. Craig WA (1998) Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing in mice and men. Clin Infect Dis 26:1–10

    Article  CAS  PubMed  Google Scholar 

  3. Muller AE, Punt N, Mouton JW (2013) Optimal exposures of ceftazidime predict the probability of microbiological and clinical outcome in the treatment of nosocomial pneumonia. J Antimicrob Chemother 68:900–906

    Article  CAS  PubMed  Google Scholar 

  4. Craig WA, Ebers SC (1992) Continuous infusion of beta-lactam antibiotics. Antimicrob Agents Chemother 36:2577–2583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kasiakou SK, Sermaides GJ, Michalapoulos A, Soteriades ES, Falagas ME (2005) Continuous versus intermittent intravenous administration of antibiotics: a meta-analysis of randomised controlled trials. Lancet Infect Dis 5:581–589

    Article  CAS  PubMed  Google Scholar 

  6. Roberts JA, Lipman J, Blot S, Rello J (2008) Better outcomes through continuous infusion in time-dependent antibiotics to critically ill patients? Curr Opin Crit Care 14:390–396

    Article  PubMed  Google Scholar 

  7. Roberts JA, Webb S, Paterson D, Ho KM, Lipman J (2009) A systematic review on clinical benefits of continuous administration of β-lactam antibiotics. Crit Care Med 37:2071–2078

    Article  CAS  PubMed  Google Scholar 

  8. MacGowan A (2011) Revisiting beta-lactam- PK/PD improves dosing of old antibiotics. Curr Opin Pharmacol 11:470–476

    Article  CAS  PubMed  Google Scholar 

  9. Abdul-Aziz MH, Staatz CE, Kirkpatrick CMJ, Lipman J, Roberts JA (2011) Continuous infusion vs. Bolus dosing: implications for beta-lactam antibiotics. Minerva Anesthesiol 77:1–2

    Google Scholar 

  10. Tamma PD, Pucha N, Suh YD, van Arendonk KJ, Rinke ML (2001) Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomize, controlled trials. BMC Infect Dis 11:181–192

    Article  Google Scholar 

  11. Dulhunty JM, Roberts JA, Davis JS et al (2013) Continuous infusion of beta lactam antibiotics in severe sepsis: a multicenter double-blind, randomised controlled trial. Clin Infect Dis 56:236–244

    Article  CAS  PubMed  Google Scholar 

  12. Falagas EM, Tansarli GS, Ikawa K, Vardakas KZ (2013) Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam a systematic review and meta-analysis. Clin Infect Dis 56:272–282

    Article  CAS  PubMed  Google Scholar 

  13. Brody TM, Larner J, Minneman KP (1998) Human pharmacology—molecular to clinical. Mosby, St Louis

    Google Scholar 

  14. Shaffer CL, Davey AM, Ransom JL, Brown YL, Gal P (1998) Ampicillin-induced neurotoxicity in very-low-birth-weight neonates. Ann Pharmacother 32:482–484

    Article  CAS  PubMed  Google Scholar 

  15. Jones DP, Gaber L, Nilsson GR (1993) Acute renal failure following amoxicillin overdose. Clin Pediatr (Phila) 32:735–739

    Article  CAS  Google Scholar 

  16. Huisman-de Boer JJ, van den Anker JN, Voel M, Goessens WHF, Schoemaker RC, de Groot R (1995) Amoxicillin pharmacokinetics in preterm infants with gestational ages less than 32 weeks. Antimicrob Agents Chemother 39:431–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Charles BG, Preechagoon Y, Lee TC, Steer PA, Flenady VJ, Debuse N (1997) Population pharmacokinetics of intravenous amoxicillin in very low birth weight infants. J Pharm Sci 86:1288–1292

    Article  CAS  PubMed  Google Scholar 

  18. Pullen J, Stolk LM, Nieman FH, Degraeuwe PL, van Tiel FH, Zimmermann LJ (2006) Population pharmacokinetics and dosing of amoxicillin in (pre)term neonates. Ther Drug Monit 28:226–231

    Article  CAS  PubMed  Google Scholar 

  19. Pullen J, Driessen M, Stolk LM, Degraeuwe PL, van Tiel FH, Neef C, Zimmermann LJ (2007) Amoxicillin pharmacokinetics in (preterm) infants aged 10 to 52 days: effect of postnatal age. Ther Drug Monit 29:376–380

    Article  CAS  PubMed  Google Scholar 

  20. Bertels RA, Semmekrot BA, Gerrits GP, Mouton JW (2008) Serum concentrations of cefotaxime and its metabolite desacetyl-cefotaxime in infants and children during continuous infusion. Infection 36:415–420

    Article  CAS  PubMed  Google Scholar 

  21. Muller AE, Dörr PJ, Mouton JW, De Jongh J, Oostvogel PM, Steegers EAP et al (2008) The influence of labour on the pharmacokinetics of intravenously administered amoxicillin in pregnant women. Br J Clin Pharmacol 66:866–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Blake MJ, Castro L, Leeder JS, Kearns GL (2005) Ontogeny of drug metabolizing enzymes in the neonate. Semin Fetal Neonatal Med 10:123–138

    Article  PubMed  Google Scholar 

  23. Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE (2003) Developmental pharmacology—drug disposition, action and therapy in infants and children. N Engl J Med 349:1157–1167

    Article  CAS  PubMed  Google Scholar 

  24. Coulthard MG (1985) Maturation of glomerular filtration in preterm and mature babies. Early Hum Dev 11:281–292

    Article  CAS  PubMed  Google Scholar 

  25. Arant BS (1975) Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr 92:705–712

    Article  Google Scholar 

  26. Cook B, Hill SA, Lynn B (1982) The stability of amoxycillin sodium in intravenous infusion fluids. J Clin Hosp Pharm 7:245–250

    CAS  PubMed  Google Scholar 

  27. Concannon J, Lovitt H, Ramage M, Tai LH, McDonald C, Sunderland VB (1986) Stability of aqueous solutions of amoxicillin sodium in the frozen and liquid states. Am J Hosp Pharm 43:3027–3030

    CAS  PubMed  Google Scholar 

  28. McDonald C, Sunderland VB, Lau H, Shija R (1989) The stability of amoxicillin sodium in normal saline and glucose (5%) solutions in the liquid and frozen states. J Clin Pharm Ther 14:45–52

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Canisius Wilhelmina Hospital, Nijmegen, Netherlands

    A. van Boekholt, H. Fleuren, J. Mouton, C. Kramers, T. Sprong, P. Gerrits & B. Semmekrot

Authors
  1. A. van Boekholt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Fleuren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Mouton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Kramers
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Sprong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Gerrits
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B. Semmekrot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. Semmekrot.

Ethics declarations

Funding

No funding was obtained for this research.

Conflicts of interest

The authors have no conflicts of interest to declare.

Ethical approval

The Central Committee of Ethics (CCMO) approved the study. The study was performed following Good Clinical Practice Guidelines.

Informed consent

Written informed consent was obtained from both parents.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

van Boekholt, A., Fleuren, H., Mouton, J. et al. Serum concentrations of amoxicillin in neonates during continuous intravenous infusion. Eur J Clin Microbiol Infect Dis 35, 1007–1012 (2016). https://doi.org/10.1007/s10096-016-2630-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-016-2630-z

Keywords

Search

Navigation