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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

Abstract

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.

Keywords

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.

Notes

Acknowledgments

None.

Funding

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.

Contributors

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.

References

  1. 1.
    Laughon MM, Avant D, Tripathi N, Hornik CP, Cohen-Wolkowiez M, Clark RH, et al. Drug labeling and exposure in neonates. JAMA Pediatr. 2014;168:130–6.PubMedGoogle Scholar
  2. 2.
    Ward RM, Kern SE. Clinical trials in neonates: a therapeutic imperative. Clin Pharmacol Ther. 2009;86(6):585–7.PubMedGoogle Scholar
  3. 3.
    Food and Drug Administration Safety and Innovation Act. Public Law No. 112–144, Session No. 112. 2012;933.Google Scholar
  4. 4.
    Bizzarro MJ, Raskind C, Baltimore RS, Gallagher PG. Seventy-five years of neonatal sepsis at Yale: 1928–2003. Pediatrics. 2005;116(3):595–602.PubMedGoogle Scholar
  5. 5.
    Stoll BJ, Hansen NI, Adams-Chapman I, Fanaroff AA, Hintz SR, Vohr B, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004;292(19):2357–65.PubMedGoogle Scholar
  6. 6.
    Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am. 2013;60(2):367–89.PubMedGoogle Scholar
  7. 7.
    Ward RM, Lugo RA. Drug therapy in the newborn. In: MacDonald MG, Seshia MM, Mullett MD, editors. Avery’s neonatology: pathophysiology and management of the newborn. 6th ed. Philadelphia: Lippincott Williams and Wilkins; 2005. p. 1507–56.Google Scholar
  8. 8.
    Gardner P. Antimicrobial drug therapy in pediatric practice. Pediatr Clin North Am. 1974;21(3):617–48.PubMedGoogle Scholar
  9. 9.
    Patterson JE, Zervos MJ. High-level gentamicin resistance in Enterococcus: microbiology, genetic basis, and epidemiology. Rev Infect Dis. 1990;12(4):644–52.PubMedGoogle Scholar
  10. 10.
    Aurangzeb B, Hameed A. Neonatal sepsis in hospital-born babies: bacterial isolates and antibiotic susceptibility patterns. J Coll Physicians Surg Pak. 2003;13(11):629–32.PubMedGoogle Scholar
  11. 11.
    Bryan CS, John JF Jr, Pai MS, Austin TL. Gentamicin vs cefotaxime for therapy of neonatal sepsis. Relationship to drug resistance. Am J Dis Child. 1985;139(11):1086–9.PubMedGoogle Scholar
  12. 12.
    Cordero L, Sananes M, Ayers LW. Bloodstream infections in a neonatal intensive-care unit: 12 years’ experience with an antibiotic control program. Infect Control Hosp Epidemiol. 1999;20(4):242–6.PubMedGoogle Scholar
  13. 13.
    D’Angio CT, McGowan KL, Baumgart S, St Geme J, Harris MC. Surface colonization with coagulase-negative staphylococci in premature neonates. J Pediatr. 1989;114(6):1029–34.PubMedGoogle Scholar
  14. 14.
    Friedman S, Shah V, Ohlsson A, Matlow AG. Neonatal escherichia coli infections: concerns regarding resistance to current therapy. Acta Paediatr. 2000;89(6):686–9.PubMedGoogle Scholar
  15. 15.
    Toltzis P, Dul MJ, Hoyen C, Salvator A, Walsh M, Zetts L, et al. The effect of antibiotic rotation on colonization with antibiotic-resistant bacilli in a neonatal intensive care unit. Pediatrics. 2002;110(4):707–11.PubMedGoogle Scholar
  16. 16.
    Singh N, Patel KM, Leger MM, Short B, Sprague BM, Kalu N, et al. Risk of resistant infections with Enterobacteriaceae in hospitalized neonates. Pediatr Infect Dis J. 2002;21(11):1029–33.PubMedGoogle Scholar
  17. 17.
    Phillips AM, Milner RD. Tissue concentrations of netilmicin and gentamicin in neonates. J Infect Dis. 1984;149(3):474.PubMedGoogle Scholar
  18. 18.
    Fisk KL. A review of gentamicin use in neonates. Neonatal Netw. 1993;12(7):19–23 (quiz 4-8).PubMedGoogle Scholar
  19. 19.
    de Cos MA, Gomez-Ullate J, Gomez F, Armijo JA. Time course of trough serum gentamicin concentrations in preterm and term neonates. Clin Pharmacokinet. 1992;23(5):391–401.PubMedGoogle Scholar
  20. 20.
    Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26(1):1–10 quiz 1-2.PubMedGoogle Scholar
  21. 21.
    McCracken GH Jr. Clinical pharmacology of gentamicin in infants 2 to 24 months of age. Am J Dis Child. 1972;124(6):884–7.PubMedGoogle Scholar
  22. 22.
    McCracken GH Jr, Jones LG. Gentamicin in the neonatal period. Am J Dis Child. 1970;120(6):524–33.PubMedGoogle Scholar
  23. 23.
    McCracken GH, West NR, Horton LJ. Urinary excretion of gentamicin in the neonatal period. J Infect Dis. 1971;123(3):257–62.PubMedGoogle Scholar
  24. 24.
    Koren G, James A, Perlman M. A simple method for the estimation of glomerular filtration rate by gentamicin pharmacokinetics during routine drug monitoring in the newborn. Clin Pharmacol Ther. 1985;38(6):680–5.PubMedGoogle Scholar
  25. 25.
    Assael BM, Gianni V, Marini A, Peneff P, Sereni F. Gentamicin dosage in preterm and term neonates. Arch Dis Child. 1977;52(11):883–6.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Rameis H, Popow C, Graninger W. Gentamicin monitoring in low-birth-weight newborns. Biol Res Pregnancy Perinatol. 1983;4(3):123–6.PubMedGoogle Scholar
  27. 27.
    Koren G, Leeder S, Harding E, Jacques D, MacLeod SM. Optimization of gentamicin therapy in very low birth weight infants. Pediatr Pharmacol (New York). 1985;5(1):79–87.Google Scholar
  28. 28.
    Pons G, d’Athis P, Rey E, de Lauture D, Richard MO, Badoual J, et al. Gentamicin monitoring in neonates. Ther Drug Monit. 1988;10(4):421–7.PubMedGoogle Scholar
  29. 29.
    Nakae S, Yamada M, Ito T, Chiba Y, Sasaki E, Sakamoto M, et al. Gentamicin dosing and pharmacokinetics in low birth weight infants. Tohoku J Exp Med. 1988;155(3):213–23.PubMedGoogle Scholar
  30. 30.
    Shahidullah M, Talukder MQ, Chowdhury AK, Ali S, Rashid A. Serum levels of gentamicin at peak and trough in neonates and infants. Indian J Pediatr. 1991;58(2):217–21.PubMedGoogle Scholar
  31. 31.
    Faura CC, Garcia MR, Horga JF. Changes in gentamicin serum levels and pharmacokinetic parameters in the newborn in the course of treatment with aminoglycoside. Ther Drug Monit. 1991;13(3):277–80.PubMedGoogle Scholar
  32. 32.
    Dodge WF, Jelliffe RW, Richardson CJ, McCleery RA, Hokanson JA, Snodgrass WR. Gentamicin population pharmacokinetic models for low birth weight infants using a new nonparametric method. Clin Pharmacol Ther. 1991;50(1):25–31.PubMedGoogle Scholar
  33. 33.
    Faura CC, Feret MA, Horga JF. Monitoring serum levels of gentamicin to develop a new regimen for gentamicin dosage in newborns. Ther Drug Monit. 1991;13(3):268–76.PubMedGoogle Scholar
  34. 34.
    Brion LP, Fleischman AR, Schwartz GJ. Gentamicin interval in newborn infants as determined by renal function and postconceptional age. Pediatr Nephrol. 1991;5(6):675–9.PubMedGoogle Scholar
  35. 35.
    Skopnik H, Wallraf R, Nies B, Troster K, Heimann G. Pharmacokinetics and antibacterial activity of daily gentamicin. Arch Dis Child. 1992;67(1 Spec No):57–61.PubMedCentralPubMedGoogle Scholar
  36. 36.
    Sirinavin S, McCracken GH Jr, Nelson JD. Determining gentamicin dosage in infants and children with renal failure. J Pediatr. 1980;96(2):331–4.PubMedGoogle Scholar
  37. 37.
    Reimche LD, Rooney ME, Hindmarsh KW, Gorecki DK, Remillard AJ, Sankaran K. An evaluation of gentamicin dosing according to renal function in neonates with suspected sepsis. Am J Perinatol. 1987;4(3):262–5.PubMedGoogle Scholar
  38. 38.
    Kanthawatana S, Uruwannakul K, Chotinarumon S. Gentamicin pharmacokinetics in Thai neonates: recommendation for a dosing guideline. J Med Assoc Thai. 1998;81(2):136–40.PubMedGoogle Scholar
  39. 39.
    Rocha MJ, Almeida AM, Afonso E, Martins V, Santos J, Leitao F, et al. The kinetic profile of gentamicin in premature neonates. J Pharm Pharmacol. 2000;52(9):1091–7.PubMedGoogle Scholar
  40. 40.
    Tugay S, Bircan Z, Caglayan C, Arisoy AE, Gokalp AS. Acute effects of gentamicin on glomerular and tubular functions in preterm neonates. Pediatr Nephrol. 2006;21(10):1389–92.PubMedGoogle Scholar
  41. 41.
    Edgren B, Karna P, Sciamanna D, Dolanski E. Gentamicin dosing in the newborn. Use of a one-compartment open pharmacokinetic model to individualize dosing. Dev Pharmacol Ther. 1984;7(4):263–72.PubMedGoogle Scholar
  42. 42.
    Jensen PD, Edgren BE, Brundage RC. Population pharmacokinetics of gentamicin in neonates using a nonlinear, mixed-effects model. Pharmacotherapy. 1992;12(3):178–82.PubMedGoogle Scholar
  43. 43.
    Weber W, Kewitz G, Rost KL, Looby M, Nitz M, Harnisch L. Population kinetics of gentamicin in neonates. Eur J Clin Pharmacol. 1993;44(Suppl 1):S23–5.PubMedGoogle Scholar
  44. 44.
    Garcia B, Barcia E, Perez F, Molina IT. Population pharmacokinetics of gentamicin in premature newborns. J Antimicrob Chemother. 2006;58(2):372–9.PubMedGoogle Scholar
  45. 45.
    Stolk LM, Degraeuwe PL, Nieman FH, de Wolf MC, de Boer A. Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates. Ther Drug Monit. 2002;24(4):527–31.PubMedGoogle Scholar
  46. 46.
    Kasik JW, Jenkins S, Leuschen MP, Nelson RM Jr. Postconceptional age and gentamicin elimination half-life. J Pediatr. 1985;106(3):502–5.PubMedGoogle Scholar
  47. 47.
    Thomson AH, Way S, Bryson SM, McGovern EM, Kelman AW, Whiting B. Population pharmacokinetics of gentamicin in neonates. Dev Pharmacol Ther. 1988;11(3):173–9.PubMedGoogle Scholar
  48. 48.
    Botha JH, du Preez MJ, Adhikari M. Population pharmacokinetics of gentamicin in South African newborns. Eur J Clin Pharmacol. 2003;59(10):755–9.PubMedGoogle Scholar
  49. 49.
    Szefler SJ, Wynn RJ, Clarke DF, Buckwald S, Shen D, Schentag JJ. Relationship of gentamicin serum concentrations to gestational age in preterm and term neonates. J Pediatr. 1980;97(2):312–5.PubMedGoogle Scholar
  50. 50.
    Hindmarsh KW, Nation RL, Williams GL, John E, French JN. Pharmacokinetics of gentamicin in very low birth weight preterm infants. Eur J Clin Pharmacol. 1983;24(5):649–53.PubMedGoogle Scholar
  51. 51.
    Kildoo C, Modanlou HD, Komatsu G, Harralson A, Hodding J. Developmental pattern of gentamicin kinetics in very low birth weight (VLBW) sick infants. Dev Pharmacol Ther. 1984;7(6):345–56.PubMedGoogle Scholar
  52. 52.
    Hayani KC, Hatzopoulos FK, Frank AL, Thummala MR, Hantsch MJ, Schatz BM, et al. Pharmacokinetics of once-daily dosing of gentamicin in neonates. J Pediatr. 1997;131(1 Pt 1):76–80.PubMedGoogle Scholar
  53. 53.
    Krishnan L, George SA. Gentamicin therapy in preterms: a comparison of two dosage regimens. Indian Pediatr. 1997;34(12):1075–80.PubMedGoogle Scholar
  54. 54.
    Davies MW, Cartwright DW. Gentamicin dosage intervals in neonates: longer dosage interval–less toxicity. J Paediatr Child Health. 1998;34(6):577–80.PubMedGoogle Scholar
  55. 55.
    Stickland MD, Kirkpatrick CM, Begg EJ, Duffull SB, Oddie SJ, Darlow BA. An extended interval dosing method for gentamicin in neonates. J Antimicrob Chemother. 2001;48(6):887–93.PubMedGoogle Scholar
  56. 56.
    Chotigeat U, Narongsanti A, Ayudhya DP. Gentamicin in neonatal infection: once versus twice daily dosage. J Med Assoc Thai. 2001;84(8):1109–15.PubMedGoogle Scholar
  57. 57.
    Rastogi A, Agarwal G, Pyati S, Pildes RS. Comparison of two gentamicin dosing schedules in very low birth weight infants. Pediatr Infect Dis J. 2002;21(3):234–40.PubMedGoogle Scholar
  58. 58.
    Agarwal G, Rastogi A, Pyati S, Wilks A, Pildes RS. Comparison of once-daily versus twice-daily gentamicin dosing regimens in infants > or = 2500 g. J Perinatol. 2002;22(4):268–74.PubMedGoogle Scholar
  59. 59.
    Alsaedi SA. Once daily gentamicin dosing in full term neonates. Saudi Med J. 2003;24(9):978–81.PubMedGoogle Scholar
  60. 60.
    Mercado MC, Brodsky NL, McGuire MK, Hurt H. Extended interval dosing of gentamicin in preterm infants. Am J Perinatol. 2004;21(2):73–7.PubMedGoogle Scholar
  61. 61.
    Lanao JM, Calvo MV, Mesa JA, Martin-Suarez A, Carbajosa MT, Miguelez F, et al. Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates. J Antimicrob Chemother. 2004;54(1):193–8.PubMedGoogle Scholar
  62. 62.
    Kosalaraksa P, Janthep P, Jirapradittha J, Taksaphan S, Kiatchoosakun P. Once versus twice daily dose of gentamicin therapy in Thai neonates. J Med Assoc Thai. 2004;87(4):372–6.PubMedGoogle Scholar
  63. 63.
    Rao SC, Ahmed M, Hagan R. One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates. Cochrane Database Syst Rev. 2006;(1):CD005091.Google Scholar
  64. 64.
    Darmstadt GL, Hossain MM, Jana AK, Saha SK, Choi Y, Sridhar S, et al. Determination of extended-interval gentamicin dosing for neonatal patients in developing countries. Pediatr Infect Dis J. 2007;26(6):501–7.PubMedGoogle Scholar
  65. 65.
    Miranda JC, Schimmel MM, James LS, Spinelli W, Rosen TS. Gentamicin kinetics in the neonate. Pediatr Pharmacol (New York). 1985;5(1):57–61.Google Scholar
  66. 66.
    Zarowitz BJ, Wynn RJ, Buckwald S, Szefler SJ. High gentamicin trough concentrations in neonates of less than 28 weeks gestational age. Dev Pharmacol Ther. 1982;5(1–2):68–75.PubMedGoogle Scholar
  67. 67.
    Alshaikh B, Dersch-Mills D, Taylor R, Akierman AR, Yusuf K. Extended interval dosing of gentamicin in premature neonates </= 28-week gestation. Acta Paediatr. 2012;101(11):1134–9.PubMedGoogle Scholar
  68. 68.
    Mohamed AF, Nielsen EI, Cars O, Friberg LE. Pharmacokinetic-pharmacodynamic model for gentamicin and its adaptive resistance with predictions of dosing schedules in newborn infants. Antimicrob Agents Chemother. 2012;56(1):179–88.PubMedCentralPubMedGoogle Scholar
  69. 69.
    Hossain MM, Chowdhury NA, Shirin M, Saha SK, Miller-Bell M, Edwards D, et al. Simplified dosing of gentamicin for treatment of sepsis in Bangladeshi neonates. J Health Popul Nutr. 2009;27(5):640–5.PubMedCentralPubMedGoogle Scholar
  70. 70.
    Hoff DS, Wilcox RA, Tollefson LM, Lipnik PG, Commers AR, Liu M. Pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol in critically ill neonates. Pharmacotherapy. 2009;29(11):1297–305.PubMedGoogle Scholar
  71. 71.
    DiCenzo R, Forrest A, Slish JC, Cole C, Guillet R. A gentamicin pharmacokinetic population model and once-daily dosing algorithm for neonates. Pharmacotherapy. 2003;23(5):585–91.PubMedGoogle Scholar
  72. 72.
    Lopez SA, Mulla H, Durward A, Tibby SM. Extended-interval gentamicin: population pharmacokinetics in pediatric critical illness. Pediatr Crit Care Med. 2010;11(2):267–74.PubMedGoogle Scholar
  73. 73.
    Tiwari S, Rehan HS, Chandra J, Mathur NN, Singh V. Efficacy and safety of a single daily dose of gentamicin in hospitalized Indian children: a quasi-randomized trial. J Antimicrob Chemother. 2009;64(5):1096–101.PubMedGoogle Scholar
  74. 74.
    Thingvoll ES, Guillet R, Caserta M, Dicenzo R. Observational trial of a 48-hour gentamicin dosing regimen derived from Monte Carlo simulations in infants born at less than 28 weeks’ gestation. J Pediatr. 2008;153(4):530–4.PubMedGoogle Scholar
  75. 75.
    Knight JA, Davis EM, Manouilov K, Hoie EB. The effect of postnatal age on gentamicin pharmacokinetics in neonates. Pharmacotherapy. 2003;23(8):992–6.PubMedGoogle Scholar
  76. 76.
    Thomson AH, Kokwaro GO, Muchohi SN, English M, Mohammed S, Edwards G. Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya. Br J Clin Pharmacol. 2003;56(1):25–31.PubMedCentralPubMedGoogle Scholar
  77. 77.
    Vervelde ML, Rademaker CM, Krediet TG, Fleer A, van Asten P, van Dijk A. Population pharmacokinetics of gentamicin in preterm neonates: evaluation of a once-daily dosage regimen. Ther Drug Monit. 1999;21(5):514–9.PubMedGoogle Scholar
  78. 78.
    Izquierdo M, Lanao JM, Cervero L, Jimenez NV, Dominguez-Gil A. Population pharmacokinetics of gentamicin in premature infants. Ther Drug Monit. 1992;14(3):177–83.PubMedGoogle Scholar
  79. 79.
    Paisley JW, Smith AL, Smith DH. Gentamicin in newborn infants. Comparison of intramuscular and intravenous administration. Am J Dis Child. 1973;126(4):473–7.PubMedGoogle Scholar
  80. 80.
    Mulhall A. Antibiotic treatment of neonates—does route of administration matter? Dev Pharmacol Ther. 1985;8(1):1–8.PubMedGoogle Scholar
  81. 81.
    McCracken GH Jr, Threlkeld N, Thomas ML. Intravenous administration of kanamycin and gentamicin in newborn infants. Pediatrics. 1977;60(4):463–6.PubMedGoogle Scholar
  82. 82.
    Watterberg KL, Kelly HW, Angelus P, Backstrom C. The need for a loading dose of gentamicin in neonates. Ther Drug Monit. 1989;11(1):16–20.PubMedGoogle Scholar
  83. 83.
    Semchuk W, Borgmann J, Bowman L. Determination of a gentamicin loading dose in neonates and infants. Ther Drug Monit. 1993;15(1):47–51.PubMedGoogle Scholar
  84. 84.
    Gal P, Ransom JL, Weaver RL. Gentamicin in neonates: the need for loading doses. Am J Perinatol. 1990;7(3):254–7.PubMedGoogle Scholar
  85. 85.
    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(4):253–63.PubMedGoogle Scholar
  86. 86.
    Isemann BT, Kotagal UR, Mashni SM, Luckhaupt EJ, Johnson CJ. Optimal gentamicin therapy in preterm neonates includes loading doses and early monitoring. Ther Drug Monit. 1996;18(5):549–55.PubMedGoogle Scholar
  87. 87.
    Giacoia GP, Schentag JJ. Pharmacokinetics and nephrotoxicity of continuous intravenous infusion of gentamicin in low birth weight infants. J Pediatr. 1986;109(4):715–9.PubMedGoogle Scholar
  88. 88.
    Sherwin CM, McCaffrey F, Broadbent RS, Reith DM, Medlicott NJ. Discrepancies between predicted and observed rates of intravenous gentamicin delivery for neonates. J Pharm Pharmacol. 2009;61(4):465–71.PubMedGoogle Scholar
  89. 89.
    Haughey DB, Hilligoss DM, Grassi A, Schentag JJ. Two-compartment gentamicin pharmacokinetics in premature neonates: a comparison to adults with decreased glomerular filtration rates. J Pediatr. 1980;96(2):325–30.PubMedGoogle Scholar
  90. 90.
    De Cock RF, Allegaert K, Schreuder MF, Sherwin CM, de Hoog M, van den Anker JN, et al. Maturation of the glomerular filtration rate in neonates, as reflected by amikacin clearance. Clin Pharmacokinet. 2012;51(2):105–17.PubMedGoogle Scholar
  91. 91.
    Landers S, Berry PL, Kearns GL, Kaplan SL, Rudolph AJ. Gentamicin disposition and effect on development of renal function in the very low birth weight infant. Dev Pharmacol Ther. 1984;7(5):285–302.PubMedGoogle Scholar
  92. 92.
    Friedman CA, Parks BR, Rawson JE. Gentamicin disposition in asphyxiated newborns: relationship to mean arterial blood pressure and urine output. Pediatr Pharmacol (New York). 1982;2(3):189–97.Google Scholar
  93. 93.
    Bravo ME, Arancibia A, Jarpa S, Carpentier PM, Jahn AN. Pharmacokinetics of gentamicin in malnourished infants. Eur J Clin Pharmacol. 1982;21(6):499–504.PubMedGoogle Scholar
  94. 94.
    Watterberg KL, Kelly HW, Johnson JD, Aldrich M, Angelus P. Effect of patent ductus arteriosus on gentamicin pharmacokinetics in very low birth weight (less than 1,500 g) babies. Dev Pharmacol Ther. 1987;10(2):107–17.PubMedGoogle Scholar
  95. 95.
    Williams BS, Ransom JL, Gal P, Carlos RQ, Smith M, Schall SA. Gentamicin pharmacokinetics in neonates with patent ductus arteriosus. Crit Care Med. 1997;25(2):273–5.PubMedGoogle Scholar
  96. 96.
    Touw DJ, Proost JH, Stevens R, Lafeber HN, van Weissenbruch MM. Gentamicin pharmacokinetics in preterm infants with a patent and a closed ductus arteriosus. Pharm World Sci. 2001;23(5):200–4.PubMedGoogle Scholar
  97. 97.
    Southgate WM, DiPiro JT, Robertson AF. Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 1989;33(6):817–9.PubMedCentralPubMedGoogle Scholar
  98. 98.
    Cohen P, Collart L, Prober CG, Fischer AF, Blaschke TF. Gentamicin pharmacokinetics in neonates undergoing extracorporal membrane oxygenation. Pediatr Infect Dis J. 1990;9(8):562–6.PubMedGoogle Scholar
  99. 99.
    Dodge WF, Jelliffe RW, Zwischenberger JB, Bellanger RA, Hokanson JA, Snodgrass WR. Population pharmacokinetic models: effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation. Ther Drug Monit. 1994;16(6):552–9.PubMedGoogle Scholar
  100. 100.
    Munzenberger PJ, Massoud N. Pharmacokinetics of gentamicin in neonatal patients supported with extracorporeal membrane oxygenation. ASAIO Trans. 1991;37(1):16–8.PubMedGoogle Scholar
  101. 101.
    Bhatt-Mehta V, Johnson CE, Schumacher RE. Gentamicin pharmacokinetics in term neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy. 1992;12(1):28–32.PubMedGoogle Scholar
  102. 102.
    Lingvall M, Reith D, Broadbent R. The effect of sepsis upon gentamicin pharmacokinetics in neonates. Br J Clin Pharmacol. 2005;59(1):54–61.PubMedCentralPubMedGoogle Scholar
  103. 103.
    Sherwin CM, Kostan E, Broadbent RS, Medlicott NJ, Reith DM. Evaluation of the effect of intravenous volume expanders upon the volume of distribution of gentamicin in septic neonates. Biopharm Drug Dispos. 2009;30(5):276–80.PubMedGoogle Scholar
  104. 104.
    Papadatos J, Kafetzis D, Papadatos C. Influence of phototherapy on the pharmacokinetics of gentamicin. J Infect Dis. 1982;146(4):567.PubMedGoogle Scholar
  105. 105.
    Zenk KE, Miwa L, Cohen JL, Waffarn F, Huxtable RF. Effect of body weight on gentamicin pharmacokinetics in neonates. Clin Pharm. 1984;3(2):170–3.PubMedGoogle Scholar
  106. 106.
    Pacifici G. Clinical pharmacokinetics of penicillins, cephalosporins, and aminoglycosides in the neonate: a review. Pharmaceuticals. 2010;3:2568–91.PubMedCentralGoogle Scholar
  107. 107.
    Skopnik H, Wallraf R, Nies B, Troster K, Heimann G. Pharmacokinetics and antibacterial activity of daily gentamicin. Arch Dis Child. 1992;67(1 Spec No):57–61.PubMedCentralPubMedGoogle Scholar
  108. 108.
    Dahlgren JG, Anderson ET, Hewitt WL. Gentamicin blood levels: a guide to nephrotoxicity. Antimicrob Agents Chemother. 1975;8(1):58–62.PubMedCentralPubMedGoogle Scholar
  109. 109.
    Red Book. 2012 Report of the committee on infectious diseases. Elk Grove: American Academy of Pediatrics; 2012.Google Scholar
  110. 110.
    Rao SC, Srinivasjois R, Hagan R, Ahmed M. One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates. Cochrane Database Syst Rev. 2011;(11):CD005091.Google Scholar
  111. 111.
    Mohamed AF, Nielsen EI, Cars O, Friberg LE. Pharmacokinetic-pharmacodynamic model for gentamicin and its adaptive resistance with predictions of dosing schedules in newborn infants. Antimicrob Agents Chemother. 2012;56(1):179–88.PubMedCentralPubMedGoogle Scholar
  112. 112.
    Schauf V, Deveikis A, Riff L, Serota A. Antibiotic-killing kinetics of group B streptococci. J Pediatr. 1976;89(2):194–8.PubMedGoogle Scholar
  113. 113.
    Danelon C, Nestorovich EM, Winterhalter M, Ceccarelli M, Bezrukov SM. Interaction of zwitterionic penicillins with the OmpF channel facilitates their translocation. Biophys J. 2006;90(5):1617–27.PubMedCentralPubMedGoogle Scholar
  114. 114.
    Izaki K, Matsuhashi M, Strominger JL. Glycopeptide transpeptidase and d-alanine carboxypeptidase: penicillin-sensitive enzymatic reactions. Proc Natl Acad Sci U S A. 1966;55(3):656–63.PubMedCentralPubMedGoogle Scholar
  115. 115.
    de Hoog M, Mouton JW, van den Anker JN. New dosing strategies for antibacterial agents in the neonate. Semin Fetal Neonatal Med. 2005;10(2):185–94.PubMedGoogle Scholar
  116. 116.
    Tessin I, Trollfors B, Thiringer K, Larsson P. Ampicillin-aminoglycoside combinations as initial treatment for neonatal septicaemia or meningitis. A retrospective evaluation of 12 years’ experience. Acta Paediatrica Scandinavica. 1991;80(10):911–6.PubMedGoogle Scholar
  117. 117.
    Cars O. The hidden impact of antibacterial resistance in respiratory tract infection. Steering an appropriate course: principles to guide antibiotic choice. Respir Med. 2001;95(Suppl A):S20–5 discussion S6-7.PubMedGoogle Scholar
  118. 118.
    Regoes RR, Wiuff C, Zappala RM, Garner KN, Baquero F, Levin BR. Pharmacodynamic functions: a multiparameter approach to the design of antibiotic treatment regimens. Antimicrob Agents Chemother. 2004;48(10):3670–6.PubMedCentralPubMedGoogle Scholar
  119. 119.
    Craig WA. The hidden impact of antibacterial resistance in respiratory tract infection. Re-evaluating current antibiotic therapy. Respir Med. 2001;95(Suppl A):S12–9 (discussion S26-7).PubMedGoogle Scholar
  120. 120.
    Carder KR. Hypersensitivity reactions in neonates and infants. Dermatol Ther. 2005;18(2):160–75.PubMedGoogle Scholar
  121. 121.
    Marshall BC, Koch WC. Antivirals for cytomegalovirus infection in neonates and infants: focus on pharmacokinetics, formulations, dosing, and adverse events. Paediatr Drugs. 2009;11(5):309–21.PubMedGoogle Scholar
  122. 122.
    Shin HT, Chang MW. Drug eruptions in children. Curr Probl Pediatr. 2001;31(7):207–34.PubMedGoogle Scholar
  123. 123.
    Polin RA. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129(5):1006–15.PubMedGoogle Scholar
  124. 124.
    Boe RW, Williams CP, Bennett JV, Oliver TK Jr. Serum levels of methicillin and ampicillin in newborn and premature infants in relation to postnatal age. Pediatrics. 1967;39(2):194–201.PubMedGoogle Scholar
  125. 125.
    Axline SG, Yaffe SJ, Simon HJ. Clinical pharmacology of antimicrobials in premature infants. II. Ampicillin, methicillin, oxacillin, neomycin, and colistin. Pediatrics. 1967;39(1):97–107.PubMedGoogle Scholar
  126. 126.
    Silverio J, Poole JW. Serum concentrations of ampicillin in newborn infants after oral administration. Pediatrics. 1973;51(3):578–80.PubMedGoogle Scholar
  127. 127.
    Kaplan JM, McCracken GH Jr, Horton LJ, Thomas ML, Davis N. Pharmacologic studies in neonates given large dosages of ampicillin. J Pediatr. 1974;84(4):571–7.PubMedGoogle Scholar
  128. 128.
    Yoshioka H, Takimoto M, Riley HD Jr. Pharmacokinetics of ampicillin in the newborn infant. J Infect Dis. 1974;129(4):461–4.PubMedGoogle Scholar
  129. 129.
    Colburn WA, Gilbaldi M, Yoshioka H, Takimoto M, Riley HD Jr. Pharmacokinetic model for serum concentrations of ampicillin in the newborn infant. J Infect Dis. 1976;134(1):67–9.PubMedGoogle Scholar
  130. 130.
    Driessen OM, Sorgedrager N, Michel MF, Kerrebijn KF, Hermans J. Pharmacokinetic aspects of therapy with ampicillin and kanamycin in new-born infants. Eur J Clin Pharmacol. 1978;13:449–57.Google Scholar
  131. 131.
    McCracken GH Jr, Ginsburg CM, Clahsen JC, Thomas ML. Pharmacologic evaluation of orally administered antibiotics in infants and children: effect of feeding on bioavailability. Pediatrics. 1978;62(5):738–43.PubMedGoogle Scholar
  132. 132.
    Ginsburg CM, McCracken GH Jr, Thomas ML, Clahsen J. Comparative pharmacokinetics of amoxicillin and ampicillin in infants and children. Pediatrics. 1979;64(5):627–31.PubMedGoogle Scholar
  133. 133.
    Sutton AM, Turner TL, Cockburn F, McAllister TA. Pharmacokinetic study of sulbactam and ampicillin administered concomitantly by intraarterial or intravenous infusion in the newborn. Rev Infect Dis. 1986;8(Suppl 5):S518–22.PubMedGoogle Scholar
  134. 134.
    Dahl LB, Melby K, Gutteberg TJ, Storvold G. Serum levels of ampicillin and gentamycin in neonates of varying gestational age. Eur J Pediatr. 1986;145(3):218–21.PubMedGoogle Scholar
  135. 135.
    Koren G. Therapeutic drug monitoring principles in the neonate. National Academy of Clinical Biochemistry. Clin Chem. 1997;43(1):222–7.PubMedGoogle Scholar
  136. 136.
    Huang NN, High RH. Comparison of serum levels following the administration of oral and parenteral preparations of penicillin to infants and children of various age groups. J Pediatr. 1953;42(6):657–8.PubMedGoogle Scholar
  137. 137.
    Ehrnebo M, Agurell S, Jalling B, Boreus LO. Age differences in drug binding by plasma proteins: studies on human foetuses, neonates and adults. Eur J Clin Pharmacol. 1971;3(4):189–93.PubMedGoogle Scholar
  138. 138.
    Paediatric Formulary Committee. BNF for children 2011–2012. London: BMJ Group, Pharmaceutical Press and RCPCH Publications; 2011.Google Scholar
  139. 139.
    Noya FJD. Antibiotic usage in neonates. Semin Pediatr Infect Dis. 1998;9(4):322–9.Google Scholar
  140. 140.
    Jacqz-Aigrain E, Zhao W, Sharland M, van den Anker JN. Use of antibacterial agents in the neonate: 50 years of experience with vancomycin administration. Semin Fetal Neonatal Med. 2013;18(1):28–34.PubMedGoogle Scholar
  141. 141.
    Pawlotsky F, Thomas A, Kergueris MF, Debillon T, Roze JC. Constant rate infusion of vancomycin in premature neonates: a new dosage schedule. Br J Clin Pharmacol. 1998;46(2):163–7.PubMedCentralPubMedGoogle Scholar
  142. 142.
    Camaione L, Elliott K, Mitchell-Van Steele A, Lomaestro B, Pai MP. Vancomycin dosing in children and young adults: back to the drawing board. Pharmacotherapy. 2013;33(12):1278–87.PubMedGoogle Scholar
  143. 143.
    de Hoog M, Mouton JW, van den Anker JN. Vancomycin: pharmacokinetics and administration regimens in neonates. Clin Pharmacokinet. 2004;43(7):417–40.PubMedGoogle Scholar
  144. 144.
    Frymoyer A, Hersh AL, Benet LZ, Guglielmo BJ. Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus infections is inadequate. Pediatr Infect Dis J. 2009;28(5):398–402.PubMedCentralPubMedGoogle Scholar
  145. 145.
    Welsh KJ, Abbott AN, Lewis EM, Gardiner JM, Kruzel MC, Lewis CT, et al. Clinical characteristics, outcomes, and microbiologic features associated with methicillin-resistant Staphylococcus aureus bacteremia in pediatric patients treated with vancomycin. J Clin Microbiol. 2010;48(3):894–9.PubMedCentralPubMedGoogle Scholar
  146. 146.
    Marques-Minana MR, Saadeddin A, Peris JE. Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline. Br J Clin Pharmacol. 2010;70(5):713–20.PubMedCentralPubMedGoogle Scholar
  147. 147.
    Gordon CL, Thompson C, Carapetis JR, Turnidge J, Kilburn C, Currie BJ. Trough concentrations of vancomycin: adult therapeutic targets are not appropriate for children. Pediatr Infect Dis J. 2012;31(12):1269–71.PubMedGoogle Scholar
  148. 148.
    Eiland LS, English TM, Eiland EH 3rd. Assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. Ann Pharmacother. 2011;45(5):582–9.PubMedGoogle Scholar
  149. 149.
    Frymoyer A, Guglielmo BJ, Wilson SD, Scarpace SB, Benet LZ, Hersh AL. Impact of a hospitalwide increase in empiric pediatric vancomycin dosing on initial trough concentrations. Pharmacotherapy. 2011;31(9):871–6.PubMedCentralPubMedGoogle Scholar
  150. 150.
    Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18–55.PubMedGoogle Scholar
  151. 151.
    Lasky T, Greenspan J, Ernst FR, Gonzalez L. Pediatric vancomycin use in 421 hospitals in the United States, 2008. PLoS One. 2012;7(8):e43258.PubMedCentralPubMedGoogle Scholar
  152. 152.
    Kadambari S, Heath PT, Sharland M, Lewis S, Nichols A, Turner MA. Variation in gentamicin and vancomycin dosage and monitoring in UK neonatal units. J Antimicrob Chemother. 2011;66(11):2647–50.PubMedGoogle Scholar
  153. 153.
    Frymoyer A, Guglielmo BJ, Hersh AL. Desired vancomycin trough serum concentration for treating invasive methicillin-resistant Staphylococcal infections. Pediatr Infect Dis J. 2013;32(10):1077–9.PubMedGoogle Scholar
  154. 154.
    Le J, Bradley JS, Murray W, Romanowski GL, Tran TT, Nguyen N, et al. Improved vancomycin dosing in children using area under the curve exposure. Pediatr Infect Dis J. 2013;32(4):e155–63.PubMedCentralPubMedGoogle Scholar
  155. 155.
    Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18–55.PubMedGoogle Scholar
  156. 156.
    Frymoyer A, Hersh AL, Coralic Z, Benet LZ, Joseph Guglielmo B. Prediction of vancomycin pharmacodynamics in children with invasive methicillin-resistant Staphylococcus aureus infections: a Monte Carlo simulation. Clin Ther. 2010;32(3):534–42.PubMedCentralPubMedGoogle Scholar
  157. 157.
    Ward RM, Allegaert K, de Groot R, van den Anker JN. Commentary: continuous infusion of vancomycin in neonates: to use or not to use remains the question. Pediatr Infect Dis J. Epub 2013 Dec 30.Google Scholar
  158. 158.
    van den Anker JN. Getting the dose of vancomycin right in the neonate. Int J Clin Pharmacol Ther. 2011;49(4):247–9.PubMedGoogle Scholar
  159. 159.
    Butterfield JM, Patel N, Pai MP, Rosano TG, Drusano GL, Lodise TP. Refining vancomycin protein binding estimates: identification of clinical factors that influence protein binding. Antimicrob Agents Chemother. 2011;55(9):4277–82.PubMedCentralPubMedGoogle Scholar
  160. 160.
    Rodvold KA, Everett JA, Pryka RD, Kraus DM. Pharmacokinetics and administration regimens of vancomycin in neonates, infants and children. Clin Pharmacokinet. 1997;33(1):32–51.PubMedGoogle Scholar
  161. 161.
    Stockmann C, Sherwin CM, Zobell JT, Lubsch L, Young DC, Olson J, et al. Population pharmacokinetics of intermittent vancomycin in children with cystic fibrosis. Pharmacotherapy. 2013;33(12):1288–96.PubMedGoogle Scholar
  162. 162.
    Anderson BJ, Allegaert K, Van den Anker JN, Cossey V, Holford NH. Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance. Br J Clin Pharmacol. 2007;63(1):75–84.PubMedCentralPubMedGoogle Scholar
  163. 163.
    De Cock RF, Allegaert K, Schreuder MF, Sherwin CM, de Hoog M, van den Anker JN, et al. Maturation of the glomerular filtration rate in neonates, as reflected by amikacin clearance. Clin Pharmacokinet. 2012;51(2):105–17.PubMedGoogle Scholar
  164. 164.
    Smits A, Kulo A, de Hoon JN, Allegaert K. Pharmacokinetics of drugs in neonates: pattern recognition beyond compound specific observations. Curr Pharm Des. 2012;18(21):3119–46.PubMedGoogle Scholar
  165. 165.
    James A, Koren G, Milliken J, Soldin S, Prober C. Vancomycin pharmacokinetics and dose recommendations for preterm infants. Antimicrob Agents Chemother. 1987;31(1):52–4.PubMedCentralPubMedGoogle Scholar
  166. 166.
    Marsot A, Boulamery A, Bruguerolle B, Simon N. Vancomycin: a review of population pharmacokinetic analyses. Clin Pharmacokinet. 2012;51(1):1–13.PubMedGoogle Scholar
  167. 167.
    Oudin C, Vialet R, Boulamery A, Martin C, Simon N. Vancomycin prescription in neonates and young infants: toward a simplified dosage. Arch Dis Child Fetal Neonatal Ed. 2011;96(5):F365–70.PubMedGoogle Scholar
  168. 168.
    de Hoog M, Schoemaker RC, Mouton JW, van den Anker JN. Vancomycin population pharmacokinetics in neonates. Clin Pharmacol Ther. 2000;67(4):360–7.PubMedGoogle Scholar
  169. 169.
    Zhao W, Kaguelidou F, Biran V, Zhang D, Allegaert K, Capparelli EV, et al. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings. Br J Clin Pharmacol. Epub 2012 Aug 1. doi: 10.1111/j.1365-2125.2012.04406.x.
  170. 170.
    Spears RL, Koch R. The use of vancomycin in pediatrics. Antibiot Ann. 1959;7:798–803.PubMedGoogle Scholar
  171. 171.
    Rana D, Abughali N, Kumar D, Super DM, Jacobs MR, Kumar ML. Staphylococcus aureus, including community-acquired methicillin-resistant S. aureus, in a level III NICU: 2001 to 2008. Am J Perinatol. 2012;29(6):401–8.PubMedGoogle Scholar
  172. 172.
    Venkatesh MP, Placencia F, Weisman LE. Coagulase-negative staphylococcal infections in the neonate and child: an update. Semin Pediatr Infect Dis. 2006;17(3):120–7.PubMedGoogle Scholar
  173. 173.
    Broome L, So TY. An evaluation of initial vancomycin dosing in infants, children, and adolescents. Int J Pediatr. 2011;2011:470364.PubMedCentralPubMedGoogle Scholar
  174. 174.
    Sammons HM, Starkey E. Vancomycin use in neonates and children: evidence-based practice is needed. Arch Dis Child. 2013;98(6):447–8.PubMedGoogle Scholar
  175. 175.
    Goutelle S, Neely M, Bleyzac N. Comment: assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. Ann Pharmacother. 2011;45(9):1171–2.PubMedGoogle Scholar
  176. 176.
    Crumby T, Rinehart E, Carby MC, Kuhl D, Talati AJ. Pharmacokinetic comparison of nomogram-based and individualized vancomycin regimens in neonates. Am J Health Syst Pharm. 2009;66(2):149–53.PubMedGoogle Scholar
  177. 177.
    Myers AL, Gaedigk A, Dai H, James LP, Jones BL, Neville KA. Defining risk factors for red man syndrome in children and adults. Pediatr Infect Dis J. 2012;31(5):464–8.PubMedCentralPubMedGoogle Scholar
  178. 178.
    Samiee-Zafarghandy S, van den Anker JN. Do we really need continuous vancomycin infusion in neonates? Arch Dis Child. 2013;98(12):1023–4.PubMedGoogle Scholar
  179. 179.
    Patel AD, Anand D, Lucas C, Thomson AH. Continuous infusion of vancomycin in neonates. Arch Dis Child. 2013;98(6):478–9.PubMedGoogle Scholar
  180. 180.
    Chamberlain J, Coombes JD, Dell D, Fromson JM, Ings RJ, Macdonald CM, et al. Metabolism of cefotaxime in animals and man. J Antimicrob Chemother. 1980;6(Suppl A):69–78.PubMedGoogle Scholar
  181. 181.
    Ings RM, Reeves DS, White LO, Bax RP, Bywater MJ, Holt HA. The human pharmacokinetics of cefotaxime and its metabolites and the role of renal tubular secretion on their elimination. J Pharmacokinet Biopharm. 1985;13(2):121–42.PubMedGoogle Scholar
  182. 182.
    Schrinner E, Limbert M, Penasse L, Lutz A. Antibacterial activity of cefotaxime and other newer cephalosporins (in vitro and in vivo). J Antimicrob Chemother. 1980;6(Suppl A):25–30.PubMedGoogle Scholar
  183. 183.
    Mitsuhashi S, Inoue M, Masuyoshi S. Antibacterial activity of cefotaxime. J Antimicrob Chemother. 1980;6(Suppl A):37–46.PubMedGoogle Scholar
  184. 184.
    Labia R, Kazmierczak A, Guionie M, Masson JM. Some bacterial proteins with affinity for cefotaxime. J Antimicrob Chemother. 1980;6(Suppl A):19–23.PubMedGoogle Scholar
  185. 185.
    Plosker GL, Foster RH, Benfield P. Cefotaxime. A pharmacoeconomic review of its use in the treatment of infections. Pharmacoeconomics. 1998;13(1 Pt 1):91–106.PubMedGoogle Scholar
  186. 186.
    Trang JM, Jacobs RF, Kearns GL, Brown AL, Wells TG, Underwood FL, et al. Cefotaxime and desacetylcefotaxime pharmacokinetics in infants and children with meningitis. Antimicrob Agents Chemother. 1985;28(6):791–5.PubMedCentralPubMedGoogle Scholar
  187. 187.
    Bergan T. Pharmacokinetic properties of the cephalosporins. Drugs. 1987;34(Suppl 2):89–104.PubMedGoogle Scholar
  188. 188.
    Kearns GL, Young RA. Pharmacokinetics of cefotaxime and desacetylcefotaxime in the young. Diagn Microbiol Infect Dis. 1995;22(1–2):97–104.PubMedGoogle Scholar
  189. 189.
    Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death. Pediatrics. 2006;117(1):67–74.PubMedGoogle Scholar
  190. 190.
    Kafetzis DA, Brater DC, Kapiki AN, Papas CV, Dellagrammaticas H, Papadatos CJ. Treatment of severe neonatal infections with cefotaxime. Efficacy and pharmacokinetics. J Pediatr. 1982;100(3):483–9.PubMedGoogle Scholar
  191. 191.
    Schaad UB, McCracken GH Jr, Loock CA, Thomas ML. Pharmacokinetics and bacteriologic efficacy of moxalactam, cefotaxime, cefoperazone, and rocephin in experimental bacterial meningitis. J Infect Dis. 1981;143(2):156–63.PubMedGoogle Scholar
  192. 192.
    Baird-Lambert J, Doyle PE, Thomas D, Cvejic M, Buchanan N. Pharmacokinetics of cefotaxime in neonates. J Antimicrob Chemother. 1984;13(5):471–7.PubMedGoogle Scholar
  193. 193.
    Aujard Y, Brion F, Jacqz-Aigrain E, Kasse MC, Chretien P, Criqui C, et al. Pharmacokinetics of cefotaxime and desacetylcefotaxime in the newborn. Diagn Microbiol Infect Dis. 1989;12(1):87–91.PubMedGoogle Scholar
  194. 194.
    de Louvois J, Mulhall A, Hurley R. The safety and pharmacokinetics of cefotaxime in the treatment of neonates. Pediatr Pharmacol (New York). 1982;2(4):275–84.Google Scholar
  195. 195.
    von Hattingberg HM, Marget W, Belohradsky BH, Roos R. Pharmacokinetics of cefotaxime in neonates and children: clinical aspects. J Antimicrob Chemother. 1980;6(Suppl A):113–8.Google Scholar
  196. 196.
    Crooks J, White LO, Burville LJ, Speidel BD, Reeves DS. Pharmacokinetics of cefotaxime and desacetyl-cefotaxime in neonates. J Antimicrob Chemother. 1984;14(Suppl B):97–101.PubMedGoogle Scholar
  197. 197.
    Gouyon JB, Pechinot A, Safran C, Chretien P, Sandre D, Kazmierczak A. Pharmacokinetics of cefotaxime in preterm infants. Dev Pharmacol Ther. 1990;14(1):29–34.PubMedGoogle Scholar
  198. 198.
    Kearns GL, Jacobs RF, Thomas BR, Darville TL, Trang JM. Cefotaxime and desacetylcefotaxime pharmacokinetics in very low birth weight neonates. J Pediatr. 1989;114(3):461–7.PubMedGoogle Scholar
  199. 199.
    Kafetzis DA, Brater DC, Kanarios J, Sinaniotis CA, Papadatos CJ. Clinical pharmacology of cefotaxime in pediatric patients. Antimicrob Agents Chemother. 1981;20(4):487–90.PubMedCentralPubMedGoogle Scholar
  200. 200.
    Begue P, Safran C, Quiniou F, Lasfargues G, Quinet B. Comparative pharmacokinetics of four new cephalosporins: moxalactam, cefotaxime, cefoperazone and ceftazidime in neonates. Dev Pharmacol Ther. 1984;7(Suppl 1):105–8.PubMedGoogle Scholar
  201. 201.
    Ahsman MJ, Wildschut ED, Tibboel D, Mathot RA. Pharmacokinetics of cefotaxime and desacetylcefotaxime in infants during extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 2010;54(5):1734–41.PubMedCentralPubMedGoogle Scholar
  202. 202.
    Odio CM. Cefotaxime for treatment of neonatal sepsis and meningitis. Diagn Microbiol Infect Dis. 1995;22(1–2):111–7.PubMedGoogle Scholar
  203. 203.
    Muller-Pebody B, Johnson AP, Heath PT, Gilbert RE, Henderson KL, Sharland M. Empirical treatment of neonatal sepsis: are the current guidelines adequate? Arch Dis Child Fetal Neonatal Ed. 2011;96(1):F4–8.PubMedGoogle Scholar
  204. 204.
    Cotten CM, McDonald S, Stoll B, Goldberg RN, Poole K, Benjamin DK Jr. The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth-weight infants. Pediatrics. 2006;118(2):717–22.PubMedGoogle Scholar
  205. 205.
    Stockmann C, Spigarelli MG, Campbell SC, Constance JE, Courter JD, Thorell EA, et al. Considerations in the pharmacologic treatment and prevention of neonatal sepsis. Paediatr Drugs. 2014;16(1):67–81.PubMedGoogle Scholar
  206. 206.
    APP Pharmaceuticals Ltd. Gentamicin Injection, USP. 2008. http://www.baxter.ca/en/downloads/product_information/GENTAMICIN(E)_PM_AUG282012_EN.pdf. Accessed 1 Nov 2013.
  207. 207.
    Kaplan JM, McCracken GH Jr, Horton LJ, Thomas ML, Davis N. Pharmacologic studies in neonates given large dosages of ampicillin. J Pediatr. 1974;84(4):571–7.PubMedGoogle Scholar
  208. 208.
    Izaki K, Matsuhashi M, Strominger JL. Glycopeptide transpeptidase and d-alanine carboxypeptidase: penicillin-sensitive enzymatic reactions. Proc Natl Acad Sci USA. 1966;55(3):656–63.PubMedCentralPubMedGoogle Scholar
  209. 209.
    Marques-Minana MR, Saadeddin A, Peris JE. Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline. Br J Clin Pharmacol. 2010;70(5):713–20.PubMedCentralPubMedGoogle Scholar
  210. 210.
    Croes S, Stolk LM. Vancomycin therapeutic guidelines: closer examination of neonatal pharmacokinetics. Clin Infect Dis. 2011;53(9):966–7.PubMedGoogle Scholar
  211. 211.
    Boger DL. Vancomycin, teicoplanin, and ramoplanin: synthetic and mechanistic studies. Med Res Rev. 2001;21(5):356–81.PubMedGoogle Scholar
  212. 212.
    West-Ward Pharmaceuticals. Cefotaxime for injection, USP. November 2012. http://www.west-ward.com/images/files/package/Cefotaxime%20for%20Inj.%20-%20PI%20-500mg%20-%201g%20-%202g%20-%20Approved.pdf. Accessed 11 Nov 2013
  213. 213.
    Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110(2 Pt 1):285–91.PubMedGoogle Scholar
  214. 214.
    Saiman L, Ludington E, Pfaller M, Rangel-Frausto S, Wiblin RT, Dawson J, et al. Risk factors for candidemia in Neonatal Intensive Care Unit patients. The National Epidemiology of Mycosis Survey study group. Pediatr Infect Dis J. 2000;19(4):319–24.PubMedGoogle Scholar
  215. 215.
    Saxen H, Virtanen M, Carlson P, Hoppu K, Pohjavuori M, Vaara M, et al. Neonatal Candida parapsilosis outbreak with a high case fatality rate. Pediatr Infect Dis J. 1995;14(9):776–81.PubMedGoogle Scholar
  216. 216.
    Rowen JL, Atkins JT, Levy ML, Baer SC, Baker CJ. Invasive fungal dermatitis in the < or = 1000-gram neonate. Pediatrics. 1995;95(5):682–7.PubMedGoogle Scholar
  217. 217.
    Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20(1):133–63.PubMedCentralPubMedGoogle Scholar
  218. 218.
    Benjamin DK Jr, Stoll BJ, Fanaroff AA, McDonald SA, Oh W, Higgins RD, et al. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics. 2006;117(1):84–92.PubMedGoogle Scholar
  219. 219.
    Friedman S, Richardson SE, Jacobs SE, O’Brien K. Systemic Candida infection in extremely low birth weight infants: short term morbidity and long term neurodevelopmental outcome. Pediatr Infect Dis J. 2000;19(6):499–504.PubMedGoogle Scholar
  220. 220.
    Mittal M, Dhanireddy R, Higgins RD. Candida sepsis and association with retinopathy of prematurity. Pediatrics. 1998;101(4 Pt 1):654–7.PubMedGoogle Scholar
  221. 221.
    Kremer I, Naor N, Davidson S, Arbizo M, Nissenkorn I. Systemic candidiasis in babies with retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 1992;230(6):592–4.PubMedGoogle Scholar
  222. 222.
    Rowen JL. Mucocutaneous candidiasis. Semin Perinatol. 2003;27(5):406–13.PubMedGoogle Scholar
  223. 223.
    Coukell AJ, Brogden RN. Liposomal amphotericin B. Therapeutic use in the management of fungal infections and visceral leishmaniasis. Drugs. 1998;55(4):585–612.PubMedGoogle Scholar
  224. 224.
    Chapman RL. Prevention and treatment of Candida infections in neonates. Semin Perinatol. 2007;31(1):39–46.PubMedGoogle Scholar
  225. 225.
    Bliss JM, Wellington M, Gigliotti F. Antifungal pharmacotherapy for neonatal candidiasis. Semin Perinatol. 2003;27(5):365–74.PubMedGoogle Scholar
  226. 226.
    Hamilton-Miller JM. Chemistry and biology of the polyene macrolide antibiotics. Bacteriol Rev. 1973;37(2):166–96.Google Scholar
  227. 227.
    Janknegt R, de Marie S, Bakker-Woudenberg IA, Crommelin DJ. Liposomal and lipid formulations of amphotericin B. Clinical pharmacokinetics. Clin Pharmacokinet. 1992;23(4):279–91.PubMedGoogle Scholar
  228. 228.
    Gallis HA, Drew RH, Pickard WW. Amphotericin B: 30 years of clinical experience. Rev Infect Dis. 1990;12(2):308–29.PubMedGoogle Scholar
  229. 229.
    Linder N, Klinger G, Shalit I, Levy I, Ashkenazi S, Haski G, et al. Treatment of candidaemia in premature infants: comparison of three amphotericin B preparations. J Antimicrob Chemother. 2003;52(4):663–7.PubMedGoogle Scholar
  230. 230.
    Baley JE, Meyers C, Kliegman RM, Jacobs MR, Blumer JL. Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-fluorocytosine in neonates. J Pediatr. 1990;116(5):791–7.PubMedGoogle Scholar
  231. 231.
    Turkova A, Roilides E, Sharland M. Amphotericin B in neonates: deoxycholate or lipid formulation as first-line therapy—is there a ‘right’ choice? Curr Opin Infect Dis. 2011;24(2):163–71.PubMedGoogle Scholar
  232. 232.
    Le J, Adler-Shohet FC, Nguyen C, Lieberman JM. Nephrotoxicity associated with amphotericin B deoxycholate in neonates. Pediatr Infect Dis J. 2009;28(12):1061–3.PubMedGoogle Scholar
  233. 233.
    Turcu R, Patterson MJ, Omar S. Influence of sodium intake on Amphotericin B-induced nephrotoxicity among extremely premature infants. Pediatr Nephrol. 2009;24(3):497–505.PubMedGoogle Scholar
  234. 234.
    Holler B, Omar SA, Farid MD, Patterson MJ. Effects of fluid and electrolyte management on amphotericin B-induced nephrotoxicity among extremely low birth weight infants. Pediatrics. 2004;113(6):e608–16.PubMedGoogle Scholar
  235. 235.
    Starke JR, Mason EO Jr, Kramer WG, Kaplan SL. Pharmacokinetics of amphotericin B in infants and children. J Infect Dis. 1987;155(4):766–74.PubMedGoogle Scholar
  236. 236.
    Hall JE, Cox F, Karlson K, Robertson A. Amphotericin B dosage for disseminated candidiasis in premature infants. J Perinatol. 1987;7(3):194–8.PubMedGoogle Scholar
  237. 237.
    Baley JE, Kliegman RM, Fanaroff AA. Disseminated fungal infections in very low-birth-weight infants: therapeutic toxicity. Pediatrics. 1984;73(2):153–7.PubMedGoogle Scholar
  238. 238.
    Higuchi R, Kusumoto S, Ban H, Iwahashi S, Kobayashi M, Sumiyama K, et al. Increased level/dose ratio of amphotericin-B in premature infants with renal failure. Acta Paediatr Jpn. 1993;35(3):238–42.PubMedGoogle Scholar
  239. 239.
    Steinbach WJ, Perfect J. Antifungal agents. In: Yaffe SJ, Aranda JV, editors. Neonatal and pediatric pharmacology: therapeutic principles in practice. 3rd ed. Philadelphia: Lippincot Williams & Wilkins; 2005. p. 459–62.Google Scholar
  240. 240.
    Kotwani RN, Gokhale PC, Bodhe PV, Kirodian BG, Kshirsagar NA, Pandya SK. A comparative study of plasma concentrations of liposomal amphotericin B (L-AMP-LRC-1) in adults, children and neonates. Int J Pharm. 2002;238(1–2):11–5.PubMedGoogle Scholar
  241. 241.
    Ascher SB, Smith PB, Watt K, Benjamin DK, Cohen-Wolkowiez M, Clark RH, et al. Antifungal therapy and outcomes in infants with invasive Candida infections. Pediatr Infect Dis J. 2012;31(5):439–43.PubMedCentralPubMedGoogle Scholar
  242. 242.
    Williams KM, Kearns GL. Lipid amphotericin preparations. Pediatr Infect Dis J. 2000;19(6):567–9.PubMedGoogle Scholar
  243. 243.
    Klepser ME, Wolfe EJ, Jones RN, Nightingale CH, Pfaller MA. Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans. Antimicrob Agents Chemother. 1997;41(6):1392–5.PubMedCentralPubMedGoogle Scholar
  244. 244.
    Pfaller MA, Messer SA, Hollis RJ, Jones RN, Doern GV, Brandt ME, et al. Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States. Diagn Microbiol Infect Dis. 1999;33(4):217–22.PubMedGoogle Scholar
  245. 245.
    Rowen JL, Tate JM, Nordoff N, Passarell L, McGinnis MR. Candida isolates from neonates: frequency of misidentification and reduced fluconazole susceptibility. J Clin Microbiol. 1999;37(11):3735–7.PubMedCentralPubMedGoogle Scholar
  246. 246.
    Mann PA, McNicholas PM, Chau AS, Patel R, Mendrick C, Ullmann AJ, et al. Impact of antifungal prophylaxis on colonization and azole susceptibility of Candida species. Antimicrob Agents Chemother. 2009;53(12):5026–34.PubMedCentralPubMedGoogle Scholar
  247. 247.
    Dotis J, Prasad PA, Zaoutis T, Roilides E. Epidemiology, risk factors and outcome of Candida parapsilosis bloodstream infection in children. Pediatr Infect Dis J. 2012;31(6):557–60.PubMedCentralPubMedGoogle Scholar
  248. 248.
    Mandras N, Tullio V, Allizond V, Scalas D, Banche G, Roana J, et al. In vitro activities of fluconazole and voriconazole against clinical isolates of Candida spp. determined by disk diffusion testing in Turin, Italy. Antimicrob Agents Chemother. 2009;53(4):1657–9.PubMedCentralPubMedGoogle Scholar
  249. 249.
    Pfaller MA, Messer SA, Hollis RJ, Jones RN, Diekema DJ. In vitro activities of ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6,970 clinical isolates of Candida spp. Antimicrob Agents Chemother. 2002;46(6):1723–7.PubMedCentralPubMedGoogle Scholar
  250. 250.
    Diekema DJ, Messer SA, Hollis RJ, Boyken L, Tendolkar S, Kroeger J, et al. A global evaluation of voriconazole activity tested against recent clinical isolates of Candida spp. Diagn Microbiol Infect Dis. 2009;63(2):233–6.PubMedGoogle Scholar
  251. 251.
    Kelly SL, Lamb DC, Corran AJ, Baldwin BC, Kelly DE. Mode of action and resistance to azole antifungals associated with the formation of 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol. Biochem Biophys Res Commun. 1995;207(3):910–5.PubMedGoogle Scholar
  252. 252.
    Tripathi N, Watt K, Benjamin DK Jr. Treatment and prophylaxis of invasive candidiasis. Semin Perinatol. 2012;36(6):416–23.PubMedCentralPubMedGoogle Scholar
  253. 253.
    Wildfeuer A, Laufen H, Schmalreck AF, Yeates RA, Zimmermann T. Fluconazole: comparison of pharmacokinetics, therapy and in vitro susceptibility. Mycoses. 1997;40(7–8):259–65.PubMedGoogle Scholar
  254. 254.
    Fasano C, O’Keeffe J, Gibbs D. Fluconazole treatment of neonates and infants with severe fungal infections not treatable with conventional agents. Eur J Clin Microbiol Infect Dis. 1994;13(4):351–4.PubMedGoogle Scholar
  255. 255.
    Steinbach WJ, Benjamin DK. New antifungal agents under development in children and neonates. Curr Opin Infect Dis. 2005;18(6):484–9.PubMedGoogle Scholar
  256. 256.
    Walsh TJ, Lutsar I, Driscoll T, Dupont B, Roden M, Ghahramani P, et al. Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr Infect Dis J. 2002;21(3):240–8.PubMedGoogle Scholar
  257. 257.
    Celik IH, Demirel G, Oguz SS, Uras N, Erdeve O, Dilmen U. Compassionate use of voriconazole in newborn infants diagnosed with severe invasive fungal sepsis. Eur Rev Med Pharmacol Sci. 2013;17(6):729–34.PubMedGoogle Scholar
  258. 258.
    Saxen H, Hoppu K, Pohjavuori M. Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life. Clin Pharmacol Ther. 1993;54(3):269–77.PubMedGoogle Scholar
  259. 259.
    Nahata MC, Tallian KB, Force RW. Pharmacokinetics of fluconazole in young infants. Eur J Drug Metab Pharmacokinet. 1999;24(2):155–7.PubMedGoogle Scholar
  260. 260.
    Wenzl TG, Schefels J, Hornchen H, Skopnik H. Pharmacokinetics of oral fluconazole in premature infants. Eur J Pediatr. 1998;157(8):661–2.PubMedGoogle Scholar
  261. 261.
    Wade KC, Wu D, Kaufman DA, Ward RM, Benjamin DK Jr, Sullivan JE, et al. Population pharmacokinetics of fluconazole in young infants. Antimicrob Agents Chemother. 2008;52(11):4043–9.PubMedCentralPubMedGoogle Scholar
  262. 262.
    Wade KC, Benjamin DK Jr, Kaufman DA, Ward RM, Smith PB, Jayaraman B, et al. Fluconazole dosing for the prevention or treatment of invasive candidiasis in young infants. Pediatr Infect Dis J. 2009;28(8):717–23.PubMedCentralPubMedGoogle Scholar
  263. 263.
    Stockmann C, Constance J, Roberts JK, Olsen J, Doby EH, Ampofo K, et al. Pharmacokinetics and pharmacodynamics of antifungals in children and their clinical implications. Clin Pharmacokinet. 2014 May;53(5):429-54.Google Scholar
  264. 264.
    Piper L, Smith PB, Hornik CP, Cheifetz IM, Barrett JS, Moorthy G, et al. Fluconazole loading dose pharmacokinetics and safety in infants. Pediatr Infect Dis J. 2011;30(5):375–8.PubMedCentralPubMedGoogle Scholar
  265. 265.
    Spriet I, Cosaert K, Renard M, Uyttebroeck A, Meyts I, Proesmans M, et al. Voriconazole plasma levels in children are highly variable. Eur J Clin Microbiol Infect Dis. 2011;30(2):283–7.PubMedGoogle Scholar
  266. 266.
    Almirante B, Rodriguez D. Antifungal agents in neonates: issues and recommendations. Paediatr Drugs. 2007;9(5):311–21.PubMedGoogle Scholar
  267. 267.
    Scholz I, Oberwittler H, Riedel KD, Burhenne J, Weiss J, Haefeli WE, et al. Pharmacokinetics, metabolism and bioavailability of the triazole antifungal agent voriconazole in relation to CYP2C19 genotype. Br J Clin Pharmacol. 2009;68(6):906–15.PubMedCentralPubMedGoogle Scholar
  268. 268.
    Watt KM, Cohen-Wolkowiez M, Ward RM, Benjamin DK Jr. Commentary: pediatric antifungal drug development: lessons learned and recommendations for the future. Pediatr Infect Dis J. 2012;31(6):635–7.PubMedCentralPubMedGoogle Scholar
  269. 269.
    Karlsson MO, Lutsar I, Milligan PA. Population pharmacokinetic analysis of voriconazole plasma concentration data from pediatric studies. Antimicrob Agents Chemother. 2009;53(3):935–44.PubMedCentralPubMedGoogle Scholar
  270. 270.
    Shima H, Miharu M, Osumi T, Takahashi T, Shimada H. Differences in voriconazole trough plasma concentrations per oral dosages between children younger and older than 3 years of age. Pediatr Blood Cancer. 2010;54(7):1050–2.PubMedGoogle Scholar
  271. 271.
    Doby EH, Benjamin DK Jr, Blaschke AJ, Ward RM, Pavia AT, Martin PL, et al. Therapeutic monitoring of voriconazole in children less than three years of age: a case report and summary of voriconazole concentrations for ten children. Pediatr Infect Dis J. 2012;31(6):632–5.PubMedCentralPubMedGoogle Scholar
  272. 272.
    Gerin M, Mahlaoui N, Elie C, Lanternier F, Bougnoux ME, Blanche S, et al. Therapeutic drug monitoring of voriconazole after intravenous administration in infants and children with primary immunodeficiency. Ther Drug Monit. 2011;33(4):464–6.PubMedGoogle Scholar
  273. 273.
    Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(5):503–35.PubMedGoogle Scholar
  274. 274.
    Driessen M, Ellis JB, Cooper PA, Wainer S, Muwazi F, Hahn D, et al. Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Pediatr Infect Dis J. 1996;15(12):1107–12.PubMedGoogle Scholar
  275. 275.
    Wainer S, Cooper PA, Gouws H, Akierman A. Prospective study of fluconazole therapy in systemic neonatal fungal infection. Pediatr Infect Dis J. 1997;16(8):763–7.PubMedGoogle Scholar
  276. 276.
    Healy CM, Baker CJ, Zaccaria E, Campbell JR. Impact of fluconazole prophylaxis on incidence and outcome of invasive candidiasis in a neonatal intensive care unit. J Pediatr. 2005;147(2):166–71.PubMedGoogle Scholar
  277. 277.
    Austin N, McGuire W. Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. Cochrane Database Syst Rev. 2013;4:CD003850.Google Scholar
  278. 278.
    Austin N, McGuire W. Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. Cochrane Database Syst Rev 2013;4:CD003850.Google Scholar
  279. 279.
    Garcia-Effron G, Park S, Perlin DS. Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints. Antimicrob Agents Chemother. 2009;53(1):112–22.PubMedCentralPubMedGoogle Scholar
  280. 280.
    Douglas CM. Fungal beta(1,3)-D-glucan synthesis. Med Mycol. 2001;39(Suppl 1):55–66.PubMedGoogle Scholar
  281. 281.
    Kurtz MB, Douglas CM. Lipopeptide inhibitors of fungal glucan synthase. J Med Vet Mycol. 1997;35(2):79–86.PubMedGoogle Scholar
  282. 282.
    Denning DW. Echinocandin antifungal drugs. Lancet. 2003;362(9390):1142–51.PubMedGoogle Scholar
  283. 283.
    Morrison VA. Echinocandin antifungals: review and update. Expert Rev Anti Infect Ther. 2006;4(2):325–42.PubMedGoogle Scholar
  284. 284.
    Niimi K, Monk BC, Hirai A, Hatakenaka K, Umeyama T, Lamping E, et al. Clinically significant micafungin resistance in Candida albicans involves modification of a glucan synthase catalytic subunit GSC1 (FKS1) allele followed by loss of heterozygosity. J Antimicrob Chemother. 2010;65(5):842–52.PubMedGoogle Scholar
  285. 285.
    Balashov SV, Park S, Perlin DS. Assessing resistance to the echinocandin antifungal drug caspofungin in Candida albicans by profiling mutations in FKS1. Antimicrob Agents Chemother. 2006;50(6):2058–63.PubMedCentralPubMedGoogle Scholar
  286. 286.
    Pfeiffer CD, Garcia-Effron G, Zaas AK, Perfect JR, Perlin DS, Alexander BD. Breakthrough invasive candidiasis in patients on micafungin. J Clin Microbiol. 2010;48(7):2373–80.PubMedCentralPubMedGoogle Scholar
  287. 287.
    Park S, Kelly R, Kahn JN, Robles J, Hsu MJ, Register E, et al. Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob Agents Chemother. 2005;49(8):3264–73.PubMedCentralPubMedGoogle Scholar
  288. 288.
    Chen SC, Slavin MA, Sorrell TC. Echinocandin antifungal drugs in fungal infections: a comparison. Drugs. 2011;71(1):11–41.PubMedGoogle Scholar
  289. 289.
    Smith PB, Walsh TJ, Hope W, Arrieta A, Takada A, Kovanda LL, et al. Pharmacokinetics of an elevated dosage of micafungin in premature neonates. Pediatr Infect Dis J. 2009;28(5):412–5.PubMedCentralPubMedGoogle Scholar
  290. 290.
    Benjamin DK Jr, Smith PB, Arrieta A, Castro L, Sanchez PJ, Kaufman D, et al. Safety and pharmacokinetics of repeat-dose micafungin in young infants. Clin Pharmacol Ther. 2010;87(1):93–9.PubMedCentralPubMedGoogle Scholar
  291. 291.
    Heresi GP, Gerstmann DR, Reed MD, van den Anker JN, Blumer JL, Kovanda L, et al. The pharmacokinetics and safety of micafungin, a novel echinocandin, in premature infants. Pediatr Infect Dis J. 2006;25(12):1110–5.PubMedGoogle Scholar
  292. 292.
    Natarajan G, Lulic-Botica M, Aranda JV. Refractory neonatal candidemia and high-dose micafungin pharmacotherapy. J Perinatol. 2009;29(11):738–43.PubMedGoogle Scholar
  293. 293.
    Saez-Llorens X, Macias M, Maiya P, Pineros J, Jafri HS, Chatterjee A, et al. Pharmacokinetics and safety of caspofungin in neonates and infants less than 3 months of age. Antimicrob Agents Chemother. 2009;53(3):869–75.PubMedCentralPubMedGoogle Scholar
  294. 294.
    Odio CM, Araya R, Pinto LE, Castro CE, Vasquez S, Alfaro B, et al. Caspofungin therapy of neonates with invasive candidiasis. Pediatr Infect Dis J. 2004;23(12):1093–7.PubMedGoogle Scholar
  295. 295.
    Filippi L, Poggi C, Gozzini E, Meleleo R, Mirabile L, Fiorini P. Neonatal liver abscesses due to Candida infection effectively treated with caspofungin. Acta Paediatr. 2009;98(5):906–9.PubMedGoogle Scholar
  296. 296.
    Manzar S, Kamat M, Pyati S. Caspofungin for refractory candidemia in neonates. Pediatr Infect Dis J. 2006;25(3):282–3.PubMedGoogle Scholar
  297. 297.
    Merk and Compnay Inc. Cancidas (caspofungin acetate) for injection: US prescribing information. http://www.merck.com/product/usa/pi_circulars/c/cancidas/cancidas_pi.pdf. Accessed 18 Oct 2013.
  298. 298.
    Neely M, Jafri HS, Seibel N, Knapp K, Adamson PC, Bradshaw SK, et al. Pharmacokinetics and safety of caspofungin in older infants and toddlers. Antimicrob Agents Chemother. 2009;53(4):1450–6.PubMedCentralPubMedGoogle Scholar
  299. 299.
    Li CC, Sun P, Dong Y, Bi S, Desai R, Dockendorf MF, et al. Population pharmacokinetics and pharmacodynamics of caspofungin in pediatric patients. Antimicrob Agents Chemother. 2011;55(5):2098–105.PubMedCentralPubMedGoogle Scholar
  300. 300.
    Seibel NL, Schwartz C, Arrieta A, Flynn P, Shad A, Albano E, et al. Safety, tolerability, and pharmacokinetics of Micafungin (FK463) in febrile neutropenic pediatric patients. Antimicrob Agents Chemother. 2005;49(8):3317–24.PubMedCentralPubMedGoogle Scholar
  301. 301.
    Hebert MF, Smith HE, Marbury TC, Swan SK, Smith WB, Townsend RW, et al. Pharmacokinetics of micafungin in healthy volunteers, volunteers with moderate liver disease, and volunteers with renal dysfunction. J Clin Pharmacol. 2005;45(10):1145–52.PubMedGoogle Scholar
  302. 302.
    Yanni SB, Smith PB, Benjamin DK Jr, Augustijns PF, Thakker DR, Annaert PP. Higher clearance of micafungin in neonates compared with adults: role of age-dependent micafungin serum binding. Biopharm Drug Dispos. 2011;32(4):222–32.PubMedCentralPubMedGoogle Scholar
  303. 303.
    Hope WW, Smith PB, Arrieta A, Buell DN, Roy M, Kaibara A, et al. Population pharmacokinetics of micafungin in neonates and young infants. Antimicrob Agents Chemother. 2010;54(6):2633–7.PubMedCentralPubMedGoogle Scholar
  304. 304.
    Prasad PA, Coffin SE, Leckerman KH, Walsh TJ, Zaoutis TE. Pediatric antifungal utilization: new drugs, new trends. Pediatr Infect Dis J. 2008;27(12):1083–8.PubMedGoogle Scholar
  305. 305.
    Caudle KE, Inger AG, Butler DR, Rogers PD. Echinocandin use in the neonatal intensive care unit. Ann Pharmacother. 2012;46(1):108–16.PubMedGoogle Scholar
  306. 306.
    Testoni D, Smith PB, Benjamin DK Jr. The use of antifungal therapy in neonatal intensive care. Clin Perinatol. 2012;39(1):83–98.PubMedCentralPubMedGoogle Scholar
  307. 307.
    Wurthwein G, Groll AH, Hempel G, Adler-Shohet FC, Lieberman JM, Walsh TJ. Population pharmacokinetics of amphotericin B lipid complex in neonates. Antimicrob Agents Chemother. 2005;49(12):5092–8.PubMedCentralPubMedGoogle Scholar
  308. 308.
    Evdoridou J, Roilides E, Bibashi E, Kremenopoulos G. Multifocal osteoarthritis due to Candida albicans in a neonate: serum level monitoring of liposomal amphotericin B and literature review. Infection. 1997;25(2):112–6.PubMedGoogle Scholar
  309. 309.
    Bekersky I, Fielding RM, Dressler DE, Lee JW, Buell DN, Walsh TJ. Pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate in humans. Antimicrob Agents Chemother. 2002;46(3):828–33.PubMedCentralPubMedGoogle Scholar
  310. 310.
    Driessen M, Ellis JB, Cooper PA, Wainer S, Muwazi F, Hahn D, et al. Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Pediatr Infect Dis J. 1996;15(12):1107–12.PubMedGoogle Scholar
  311. 311.
    Pfaller MA, Diekema DJ, Rex JH, Espinel-Ingroff A, Johnson EM, Andes D, et al. Correlation of MIC with outcome for Candida species tested against voriconazole: analysis and proposal for interpretive breakpoints. J Clin Microbiol. 2006;44(3):819–26.PubMedCentralPubMedGoogle Scholar
  312. 312.
    Groll AH, Walsh TJ. Caspofungin: pharmacology, safety and therapeutic potential in superficial and invasive fungal infections. Expert Opin Investig Drugs. 2001;10(8):1545–58.PubMedGoogle Scholar
  313. 313.
    Watt K, Benjamin DK Jr, Cohen-Wolkowiez M. Pharmacokinetics of antifungal agents in children. Early Hum Dev. 2011;87(Suppl 1):S61–5.PubMedCentralPubMedGoogle Scholar
  314. 314.
    Eschenauer G, Depestel DD, Carver PL. Comparison of echinocandin antifungals. Ther Clin Risk Manag. 2007;3(1):71–97.PubMedCentralPubMedGoogle Scholar
  315. 315.
    Stone JA, Xu X, Winchell GA, Deutsch PJ, Pearson PG, Migoya EM, et al. Disposition of caspofungin: role of distribution in determining pharmacokinetics in plasma. Antimicrob Agents Chemother. 2004;48(3):815–23.PubMedCentralPubMedGoogle Scholar
  316. 316.
    Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA. 2003;289(2):203–9.PubMedGoogle Scholar
  317. 317.
    Whitley RJ. The use of antiviral drugs during the neonatal period. Clin Perinatol. 2012;39(1):69–81.PubMedCentralPubMedGoogle Scholar
  318. 318.
    Kimberlin DW. Management of HSV encephalitis in adults and neonates: diagnosis, prognosis and treatment. Herpes. 2007;14(1):11–6.PubMedGoogle Scholar
  319. 319.
    Demmler GJ. Infectious Diseases Society of America and Centers for Disease Control. Summary of a workshop on surveillance for congenital cytomegalovirus disease. Rev Infect Dis. 1991;13(2):315–29.PubMedGoogle Scholar
  320. 320.
    Istas AS, Demmler GJ, Dobbins JG, Stewart JA. Surveillance for congenital cytomegalovirus disease: a report from the National Congenital Cytomegalovirus Disease Registry. Clin Infect Dis. 1995;20(3):665–70.PubMedGoogle Scholar
  321. 321.
    Griffiths P. Cytomegalovirus infection of the central nervous system. Herpes. 2004;11(Suppl 2):95a–104a.PubMedGoogle Scholar
  322. 322.
    Elion GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, Schaeffer HJ. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci U S A. 1977;74(12):5716–20.PubMedCentralPubMedGoogle Scholar
  323. 323.
    Schaeffer HJ, Beauchamp L, de Miranda P, Elion GB, Bauer DJ, Collins P. 9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group. Nature. 1978;272(5654):583–5.PubMedGoogle Scholar
  324. 324.
    Englund JA, Zimmerman ME, Swierkosz EM, Goodman JL, Scholl DR, Balfour HH Jr. Herpes simplex virus resistant to acyclovir. A study in a tertiary care center. Ann Intern Med. 1990;112(6):416–22.PubMedGoogle Scholar
  325. 325.
    Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Corey L, Gruber WC, et al. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics. 2001;108(2):230–8.PubMedGoogle Scholar
  326. 326.
    Kimberlin D, Powell D, Gruber W, Diaz P, Arvin A, Kumar M, et al. Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a phase I/II trial. Pediatr Infect Dis J. 1996;15(3):247–54.PubMedGoogle Scholar
  327. 327.
    Sampson MR, Bloom BT, Lenfestey RW, Harper B, Kashuba AD, Anand R, et al. Population pharmacokinetics of intravenous acyclovir in preterm and term infants. Pediatr Infect Dis J. 2014;33:42–9.PubMedGoogle Scholar
  328. 328.
    Blum MR, Liao SH, de Miranda P. Overview of acyclovir pharmacokinetic disposition in adults and children. Am J Med. 1982;73(1A):186–92.PubMedGoogle Scholar
  329. 329.
    Hintz M, Connor JD, Spector SA, Blum MR, Keeney RE, Yeager AS. Neonatal acyclovir pharmacokinetics in patients with herpes virus infections. Am J Med. 1982;73(1A):210–4.PubMedGoogle Scholar
  330. 330.
    Englund JA, Fletcher CV, Balfour HH Jr. Acyclovir therapy in neonates. J Pediatr. 1991;119(1 Pt 1):129–35.PubMedGoogle Scholar
  331. 331.
    Sampson MR, Bloom BT, Lenfestey RW, Harper B, Kashuba AD, Anand R, et al. Population pharmacokinetics of intravenous acyclovir in preterm and term infants. Pediatr Infect Dis J. 2014;33(1):42–9.PubMedGoogle Scholar
  332. 332.
    Rabalais GP, Nusinoff-Lehrman S, Arvin AM, Levin MJ. Antiviral susceptibilities of herpes simplex virus isolates from infants with recurrent mucocutaneous lesions after neonatal infection. Pediatr Infect Dis J. 1989;8(4):221–3.PubMedGoogle Scholar
  333. 333.
    Pinninti SG, Kimberlin DW. Neonatal herpes simplex virus infections. Pediatr Clin N Am. 2013;60(2):351–65.Google Scholar
  334. 334.
    Jones CA, Walker KS, Badawi N. Antiviral agents for treatment of herpes simplex virus infection in neonates. Cochrane Database Syst Rev. 2009;(3):CD004206.Google Scholar
  335. 335.
    Shah SS, Aronson PL, Mohamad Z, Lorch SA. Delayed acyclovir therapy and death among neonates with herpes simplex virus infection. Pediatrics. 2011;128(6):1153–60.PubMedCentralPubMedGoogle Scholar
  336. 336.
    Whitley R, Arvin A, Prober C, Burchett S, Corey L, Powell D, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med. 1991;324(7):444–9.PubMedGoogle Scholar
  337. 337.
    Kimberlin DW, Whitley RJ, Wan W, Powell DA, Storch G, Ahmed A, et al. Oral acyclovir suppression and neurodevelopment after neonatal herpes. N Engl J Med. 2011;365(14):1284–92.PubMedCentralPubMedGoogle Scholar
  338. 338.
    Long SS. In defense of empiric acyclovir therapy in certain neonates. J Pediatr. 2008;153(2):157–8.PubMedGoogle Scholar
  339. 339.
    Caviness AC, Demmler GJ, Swint JM, Cantor SB. Cost-effectiveness analysis of herpes simplex virus testing and treatment strategies in febrile neonates. Arch Pediatr Adolesc Med. 2008;162(7):665–74.PubMedGoogle Scholar
  340. 340.
    Kimberlin DW. When should you initiate acyclovir therapy in a neonate? J Pediatr. 2008;153(2):155–6.PubMedGoogle Scholar
  341. 341.
    Whitley RJ. The use of antiviral drugs during the neonatal period. Clin Perinatol. 2012;39(1):69–81.PubMedCentralPubMedGoogle Scholar
  342. 342.
    Ashton WT, Karkas JD, Field AK, Tolman RL. Activation by thymidine kinase and potent antiherpetic activity of 2′-nor-2′-deoxyguanosine (2′NDG). Biochem Biophys Res Commun. 1982;108(4):1716–21.PubMedGoogle Scholar
  343. 343.
    Martin JC, Dvorak CA, Smee DF, Matthews TR, Verheyden JP. 9-[(1,3-Dihydroxy-2-propoxy)methyl]guanine: a new potent and selective antiherpes agent. J Med Chem. 1983;26(5):759–61.PubMedGoogle Scholar
  344. 344.
    Cheng YC, Huang ES, Lin JC, Mar EC, Pagano JS, Dutschman GE, et al. Unique spectrum of activity of 9-[(1,3-dihydroxy-2-propoxy)methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1. Proc Natl Acad Sci U S A. 1983;80(9):2767–70.PubMedCentralPubMedGoogle Scholar
  345. 345.
    Field AK, Davies ME, DeWitt C, Perry HC, Liou R, Germershausen J, et al. 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine: a selective inhibitor of herpes group virus replication. Proc Natl Acad Sci U S A. 1983;80(13):4139–43.PubMedCentralPubMedGoogle Scholar
  346. 346.
    Smith KO, Galloway KS, Kennell WL, Ogilvie KK, Radatus BK. A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2. Antimicrob Agents Chemother. 1982;22(1):55–61.PubMedCentralPubMedGoogle Scholar
  347. 347.
    Lin JC, Smith MC, Pagano JS. Prolonged inhibitory effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine against replication of Epstein-Barr virus. J Virol. 1984;50(1):50–5.PubMedCentralPubMedGoogle Scholar
  348. 348.
    Cheng YC, Grill SP, Dutschman GE, Nakayama K, Bastow KF. Metabolism of 9-(1,3-dihydroxy-2-propoxymethyl)guanine, a new anti-herpes virus compound, in herpes simplex virus-infected cells. J Biol Chem. 1983;258(20):12460–4.PubMedGoogle Scholar
  349. 349.
    Sullivan V, Talarico CL, Stanat SC, Davis M, Coen DM, Biron KK. A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature. 1992;359(6390):85.PubMedGoogle Scholar
  350. 350.
    Littler E, Stuart AD, Chee MS. Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir. Nature. 1992;358(6382):160–2.PubMedGoogle Scholar
  351. 351.
    Chee MS, Lawrence GL, Barrell BG. Alpha-, beta- and gammaherpesviruses encode a putative phosphotransferase. J Gen Virol. 1989;70(Pt 5):1151–60.PubMedGoogle Scholar
  352. 352.
    Erice A. Resistance of human cytomegalovirus to antiviral drugs. Clin Microbiol Rev. 1999;12(2):286–97.PubMedCentralPubMedGoogle Scholar
  353. 353.
    Whitley RJ, Cloud G, Gruber W, Storch GA, Demmler GJ, Jacobs RF, et al. Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis. 1997;175(5):1080–6.PubMedGoogle Scholar
  354. 354.
    Kimberlin DW. Antiviral therapy for cytomegalovirus infections in pediatric patients. Semin Pediatr Infect Dis. 2002;13(1):22–30.PubMedGoogle Scholar
  355. 355.
    Jacobson MA, Gambertoglio JG, Aweeka FT, Causey DM, Portale AA. Foscarnet-induced hypocalcemia and effects of foscarnet on calcium metabolism. J Clin Endocrinol Metab. 1991;72(5):1130–5.PubMedGoogle Scholar
  356. 356.
    Kimberlin DW, Lin CY, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003;143(1):16–25.PubMedGoogle Scholar
  357. 357.
    Cocohoba JM, McNicholl IR. Valganciclovir: an advance in cytomegalovirus therapeutics. Ann Pharmacother. 2002;36(6):1075–9.PubMedGoogle Scholar
  358. 358.
    Meine Jansen CF, Toet MC, Rademaker CM, Ververs TF, Gerards LJ, van Loon AM. Treatment of symptomatic congenital cytomegalovirus infection with valganciclovir. J Perinat Med. 2005;33(4):364–6.PubMedGoogle Scholar
  359. 359.
    Muller A, Eis-Hubinger AM, Brandhorst G, Heep A, Bartmann P, Franz AR. Oral valganciclovir for symptomatic congenital cytomegalovirus infection in an extremely low birth weight infant. J Perinatol. 2008;28(1):74–6.PubMedGoogle Scholar
  360. 360.
    Schulzke S, Buhrer C. Valganciclovir for treatment of congenital cytomegalovirus infection. Eur J Pediatr. 2006;165(8):575–6.PubMedGoogle Scholar
  361. 361.
    Buonuomo PS, Maurizi P, Valentini P, Mastrangelo S, Lazzareschi I, Ridola V, et al. Successful treatment with oral valganciclovir in immunocompetent infant with gastrointestinal manifestations of cytomegalovirus infection. J Perinatol. 2006;26(10):648–9.PubMedGoogle Scholar
  362. 362.
    Kimberlin DW, Acosta EP, Sanchez PJ, Sood S, Agrawal V, Homans J, et al. Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis. 2008;197(6):836–45.PubMedGoogle Scholar
  363. 363.
    Lombardi G, Garofoli F, Villani P, Tizzoni M, Angelini M, Cusato M, et al. Oral valganciclovir treatment in newborns with symptomatic congenital cytomegalovirus infection. Eur J Clin Microbiol Infect Dis. 2009;28(12):1465–70.PubMedGoogle Scholar
  364. 364.
    Trang JM, Kidd L, Gruber W, Storch G, Demmler G, Jacobs R, et al. Linear single-dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections. NIAID Collaborative Antiviral Study Group. Clin Pharmacol Ther. 1993;53(1):15–21.PubMedGoogle Scholar
  365. 365.
    Zhou XJ, Gruber W, Demmler G, Jacobs R, Reuman P, Adler S, et al. Population pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections. NIAID Collaborative Antiviral Study Group. Antimicrob Agents Chemother. 1996;40(9):2202–5.PubMedCentralPubMedGoogle Scholar
  366. 366.
    Markham A, Faulds D. Ganciclovir. An update of its therapeutic use in cytomegalovirus infection. Drugs. 1994;48(3):455–84.PubMedGoogle Scholar
  367. 367.
    Galli L, Novelli A, Chiappini E, Gervaso P, Cassetta MI, Fallani S, et al. Valganciclovir for congenital CMV infection: a pilot study on plasma concentration in newborns and infants. Pediatr Infect Dis J. 2007;26(5):451–3.PubMedGoogle Scholar
  368. 368.
    Acosta EP, Brundage RC, King JR, Sanchez PJ, Sood S, Agrawal V, et al. Ganciclovir population pharmacokinetics in neonates following intravenous administration of ganciclovir and oral administration of a liquid valganciclovir formulation. Clin Pharmacol Ther. 2007;81(6):867–72.PubMedGoogle Scholar
  369. 369.
    Kimberlin DW, Lin CY, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003;143(1):16–25.PubMedGoogle Scholar
  370. 370.
    Oliver SE, Cloud GA, Sánchez PJ, Demmler GJ, Dankner W, Shelton M, et al. Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system. J Clin Virol. 2009;46(Suppl 4):S22–6.PubMedCentralPubMedGoogle Scholar
  371. 371.
    Nassetta L, Kimberlin D, Whitley R. Treatment of congenital cytomegalovirus infection: implications for future therapeutic strategies. J Antimicrob Chemother. 2009;63(5):862–7.PubMedCentralPubMedGoogle Scholar
  372. 372.
    Frenkel LM, Capparelli EV, Dankner WM, Xu J, Smith IL, Ballow A, et al. Oral ganciclovir in children: pharmacokinetics, safety, tolerance, and antiviral effects. The Pediatric AIDS Clinical Trials Group. J Infect Dis. 2000;182(6):1616–24.PubMedGoogle Scholar

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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