Clinical Pharmacokinetics

, Volume 53, Issue 7, pp 581–610 | Cite as

Pharmacokinetics and Pharmacodynamics of Antibacterials, Antifungals, and Antivirals Used Most Frequently in Neonates and Infants

  • Jessica K. Roberts
  • Chris Stockmann
  • Jonathan E. Constance
  • Justin Stiers
  • Michael G. Spigarelli
  • Robert M. Ward
  • Catherine M. T. SherwinEmail author
Review Article


Antimicrobials and antivirals are widely used in young infants and neonates. These patients have historically been largely excluded from clinical trials and, as a consequence, the pharmacokinetics and pharmacodynamics of commonly used antibacterials, antifungals, and antivirals are incompletely understood in this population. This review summarizes the current literature specific to neonates and infants regarding pharmacokinetic parameters and changes in neonatal development that affect antimicrobial and antiviral pharmacodynamics. Specific drug classes addressed include aminoglycosides, aminopenicillins, cephalosporins, glycopeptides, azole antifungals, echinocandins, polyenes, and guanosine analogs. Within each drug class, the pharmacodynamics, pharmacokinetics, and clinical implications and future directions for prototypical agents are discussed. β-Lactam antibacterial activity is maximized when the plasma concentration exceeds the minimum inhibitory concentration for a prolonged period, suggesting that more frequent dosing may optimize β-lactam therapy. Aminoglycosides are typically administered at longer intervals with larger doses in order to maximize exposure (i.e., area under the plasma concentration–time curve) with gestational age and weight strongly influencing the pharmacokinetic profile. Nonetheless, safety concerns necessitate therapeutic drug monitoring across the entire neonatal and young infant spectrum. Vancomycin, representing the glycopeptide class of antibacterials, has a long history of clinical utility, yet there is still uncertainty about the optimal pharmacodynamic index in neonates and young infants. The high degree of pharmacokinetic variability in this population makes therapeutic drug monitoring essential to ensure adequate therapeutic exposure. Among neonates treated with the triazole agent fluconazole, it has been speculated that loading doses may improve pharmacodynamic target attainment rates. The use of voriconazole necessitates therapeutic drug monitoring and dose adjustments for patients with hepatic dysfunction. Neonates treated with lipid-based formulations of the polyene amphotericin B may be at an increased risk of death, such that alternative antifungal agents should be considered for neonates with invasive fungal infections. Alternative antifungal agents such as micafungin and caspofungin also exhibit unique pharmacokinetic considerations in this population. Neonates rapidly eliminate micafungin and require nearly three times the normal adult dose to achieve comparable levels of systemic exposure. Conversely, peak caspofungin concentrations have been reported to be similar among neonates and adults. However, both of these drugs feature favorable safety profiles. Recent studies with acyclovir have suggested that current dosing regimens may not result in therapeutic central nervous system concentrations and more frequent dosing may be required for neonates at later postmenstrual ages. Though ganciclovir and valganciclovir demonstrate excellent activity against cytomegalovirus, they are associated with significant neutropenia. In summary, many pharmacokinetic and pharmacodynamic studies have been conducted in this vulnerable population; however, there are also substantial gaps in our knowledge that require further investigation. These studies will be invaluable in determining optimal neonatal dosing regimens that have the potential to improve clinical outcomes and decrease adverse effects associated with antimicrobial and antiviral treatments.


Vancomycin Fluconazole Cefotaxime Voriconazole Acyclovir 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





JKR is supported by the Pharmacotherapy Subspecialty Award from the Primary Children’s Medical Center Foundation. RMW is supported by NIH Grants: 1 R01 HD070795-01A1 and 5 R01 HD060559-05.

Transparency declarations

The University of Utah receives reimbursement for the conduct of a clinical trial involving micafungin. RMW receives no direct payment. All other authors declared no conflicts of interest.


JKR, CS, JEC, JS, MGS, RMW, and CMTS wrote the initial draft of the review. All authors also contributed to the reviewing and finalization of the document.


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Jessica K. Roberts
    • 1
  • Chris Stockmann
    • 1
    • 3
    • 4
  • Jonathan E. Constance
    • 1
  • Justin Stiers
    • 2
  • Michael G. Spigarelli
    • 1
    • 4
  • Robert M. Ward
    • 1
    • 2
  • Catherine M. T. Sherwin
    • 1
    Email author
  1. 1.Division of Clinical Pharmacology, Department of PediatricsUniversity of Utah School of Medicine, University of Utah Health Sciences CenterSalt Lake CityUSA
  2. 2.Division of Neonatology, Department of PediatricsUniversity of Utah School of MedicineSalt Lake CityUSA
  3. 3.Division of Infectious Diseases, Department of PediatricsUniversity of Utah School of MedicineSalt Lake CityUSA
  4. 4.Department of Pharmacology/ToxicologyUniversity of Utah College of PharmacySalt Lake CityUSA

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