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Clinical Pharmacokinetics of Antibacterial Drugs in Neonates

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Summary

Neonatal patients are surviving longer due to the rapid advances in medical knowledge and technology. Our understanding of the developmental physiology of both preterm and full term neonates has also increased. It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy.

The penicillins and cephalosporins are frequently used in neonates. Although ampicillin has replaced benzylpenicillin (penicillin G) for empirical treatment of neonatal sepsis, many of the other penicillins may be used in neonates for the management of various infections. Increased volume of distribution (Vd) and decreased total body clearance (CL) affect the disposition of penicillins and cephalosporins. Decreased renal clearance (CLR) due to decreased glomerular filtration and tubular secretion is responsible for the decreased CL for most of the β-lactams.

Aminoglycoside Vd is affected by the increased total body water content and extracellular fluid volume of neonates. The increased Vd, in part, accounts for the extended elimination half-life (t½) observed in neonates. Aminoglycoside CL is dependent on renal glomerular filtration which is markedly decreased in neonates, especially those preterm. These drugs appear to be less nephrotoxic and ototoxic in neonates than in older patients, and the role of serum concentration monitoring should be limited to specific neonatal patients.

Other antibiotics such as vancomycin, teicoplanin, chloramphenicol, rifampicin, erythromycin, clindamycin, metronidazole and cotrimoxazole (trimethoprim plus sulfamethoxazole) may be used in certain clinical situations. The emergence of staphylococcal resistance to penicillins has increased the need for vancomycin. With the exceptions of vancomycin and chloramphenicol, the efficacy and safety of these other agents in neonates have not been established. The need for serum vancomycin concentration monitoring may be limited, as with aminoglycosides, while safety concerns warrant the routine monitoring of serum chloramphenicol concentrations in neonates.

Dosing guidelines are provided, based on the pharmacokinetics of the drugs and previously published recommendations. These dosing guidelines are intended for initial therapy, and close therapeutic monitoring is recommended for maintenance dose requirements to optimise patient outcome.

There has been an enormous increase in our knowledge of neonatal physiology and drug disposition. Fortunately, many of the antibacterial drugs used in neonates (e.g. penicillins and cephalosporins) are relatively safe. It will be important to evaluate all newly developed antibiotics in neonates to assure their maximum efficacy and safety.

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References

  • Acocella G. Clinical pharmacokinetics of rifampicin. Clinical Pharmacokinetics 3: 108–127, 1978

    Article  PubMed  CAS  Google Scholar 

  • Adelman C, Linder N, Levi H. Auditory nerve and brain stem evoked response thresholds in infants treated with gentamicin as neonates. Annals of Otology, Rhinology and Larynogology 98: 283–286, 1989

    CAS  Google Scholar 

  • Agbayani MM, Khan AJ, Kemawikasit P, Rosenfeld W, Salazar D, et al. Pharmacokinetics and safety of cefamandole in newborn infants. Antimicrobial Agents and Chemotherapy 15: 674–767, 1979

    Article  PubMed  CAS  Google Scholar 

  • Arant BS. Developmental patterns of renal functional maturation compared in the human neonate. Journal of Pediatrics 92: 705–712, 1978

    Article  PubMed  CAS  Google Scholar 

  • Arbeter AM, Saccar CL, Eisner S, Sarni E, Yaffe SJ. Tobramycin sulfate elimination in premature infants. Journal of Pediatrics 103: 131–135, 1983

    Article  PubMed  CAS  Google Scholar 

  • Assael BM, Cavanna G, Jusko WJ, Marini A, et al. Multiexponential elimination of gentamicin. Developmental Pharmacology and Therapeutics 1: 171–181, 1980

    PubMed  CAS  Google Scholar 

  • Assael BM, Gianni V, Marini A, Peneff P, Sereni F. Gentamicin dosage in preterm and term neonates. Archives of Disease in Childhood 52: 883–886, 1977

    Article  PubMed  CAS  Google Scholar 

  • Aujard Y, Brion F, Jacqz-Aigrain E, Kasse MC, Chretien P, et al. Pharmacokinetics of cefotaxime and desacetylcefotaxime in the newborn. Diagnostic Microbiology and Infectious Disease 12: 87–91, 1989

    Article  PubMed  CAS  Google Scholar 

  • Axline SG, Yaffe SJ, Simon HJ. Clinical pharmacology of antimicrobials in premature infants: II. Ampicillin, methicillin, oxacillin, neomycin, and colistin. Pediatrics 39: 97–107, 1967

    PubMed  CAS  Google Scholar 

  • Baird-Lambert J, Doyle PE, Thomas D, Cvejic M, Buchanan N. Pharmacokinetics of cefotaxime in neonates. Journal of Antimicrobial Chemotherapy 13: 471–477, 1984

    Article  PubMed  CAS  Google Scholar 

  • Banner W, Gooch WM, Burckart G, Korones SB. Pharmacokinetics of nafcillin in infants with low birth weights. Antimicrobial Agents and Chemotherapy 17: 691–694, 1980

    Article  PubMed  CAS  Google Scholar 

  • Begue PC, Baron S, Challier P, Fontaine JL, Lasfargues G. Pharmacokinetic and clinical evaluation of imipenem/cilastatin in children and neonates. Scandinavian Journal of Infectious Disease (Suppl. 52): 40–45, 1987

    CAS  Google Scholar 

  • Begue P, Quiniou F, Quinet B. Efficacy and pharmacokinetics of timentin in paediatric infections. Journal of Antimicrobial Chemotherapy 17 (Suppl. C): 81–91, 1986

    Article  PubMed  Google Scholar 

  • Bell MJ, Shackelford P, Smith R, Schroeder K. Pharmacokinetics of clindamycin phosphate in the first year of life. Journal of Pediatrics 105: 482–486, 1984

    Article  PubMed  CAS  Google Scholar 

  • Bergan T. Overview of acylureidopenicillin pharmacokinetics. Scandinavian Journal of Infectious Disease (Suppl. 29): 33–48, 1981

    CAS  Google Scholar 

  • Besunder JB, Reed MD, Blumer JL. Principles of drug biodisposition in the neonate. A critical evaluation of the pharmacokinetic-pharmacodynamic interface (Part I). Clinical Pharmacokinetics 14: 189–216, 1988a

    Article  PubMed  CAS  Google Scholar 

  • Besunder JB, Reed MD, Blumer JL. Principles of drug biodis-position in the neonate. A critical evaluation of the pharmacokinetic-pharmacodynamic interface (Part II). Clinical Pharmacokinetics 14: 261–286, 1988b

    Article  PubMed  CAS  Google Scholar 

  • Blumer JL, Aronoff SC, Myers CM, O’Brien CA, Klinger JD, et al. Pharmacokinetics and cerebrospinal fluid penetration of ceftazidime in children with meningitis. Developmental Pharmacology and Therapeutics 8: 219–231, 1985

    PubMed  CAS  Google Scholar 

  • Boccazzi A, Rizzo M, Caccamo ML, Assael BM. Comparison of the concentrations of ceftazidime in the serum of newborn infants after intravenous and intramuscular administration. Antimicrobial Agents and Chemotherapy 24: 955–956, 1983

    Article  PubMed  CAS  Google Scholar 

  • Boe RW, Williams CPS, Bennett JV, Oliver TK. Serum levels of methicillin and ampicillin in newborn and premature infants in relation to postnatal age. Pediatrics 39: 194–201, 1967

    PubMed  CAS  Google Scholar 

  • Bonati M. Early neonatal drug utilization in preterm newborns in neonatal intensive care units: Italian Collaborative Group on Preterm Delivery. Developmental Pharmacology and Therapeutics 11: 1–7, 1988

    Google Scholar 

  • Bosso JA, Chan GM, Matsen JM. Cefoperazone pharmacokinetics in preterm infants. Antimicrobial Agents and Chemotherapy 23: 413–415, 1983

    Article  PubMed  CAS  Google Scholar 

  • Bradley JS. Neonatal infections. Pediatric Infectious Disease 4: 315–320, 1985

    Article  PubMed  CAS  Google Scholar 

  • Buchanan N. Aminoglycoside monitoring in neonates — a re-appraisal. Australian and New Zealand Journal of Medicine 5: 457–459, 1985

    Article  Google Scholar 

  • Buchanan N, Moodley GP. Interaction between chloramphenicol and paracetamol. British Medical Journal 2: 307–308, 1979

    Article  PubMed  CAS  Google Scholar 

  • Burns L, Hodgman J. Studies of prematures given erythromycin estolate. American Journal of Diseases of Children 106: 80–88, 1963

    Google Scholar 

  • Carlstedt BC, Uaamnuichai M, Day RB, Bowman L, Brater DC. Aminoglycoside dosing in pediatric patients. Therapeutic Drug Monitoring 11: 38–43, 1989

    Article  PubMed  CAS  Google Scholar 

  • Crooks J, White LO, Burville LJ, Speidel BD, Reeves DS. Pharmacokinetics of cefotaxime and desacetyl-cefotaxime in neonates. Journal of Antimicrobial Chemotherapy 14 (Suppl B): 97–101, 1984

    Article  PubMed  Google Scholar 

  • Deguchi Y, Koshida R. Nakashima E. Watanabe R, Taniguchi N, et al. Interindividual changes in volume of distribution of cefazolin in newborn infants and its prediction based on physiological pharmacokinetic concepts. Journal of Pharmaceutical Sciences 77: 674–678, 1988

    Article  PubMed  CAS  Google Scholar 

  • Doyle PE. Jager-Roman E, Baird-Lambert J, Cvejic M. Buchanan N. Effect of prenatal exposure to betamethasone on metronidazole elimination in premature infants. Journal of Pediatrics 101: 647, 1982

    PubMed  CAS  Google Scholar 

  • Edgren B, Karna P, Sciamanna D, Dolanski E. Gentamicin dosing in the newborn. Developmental Pharmacology and Therapeutics 7: 263–272, 1984

    PubMed  CAS  Google Scholar 

  • Edwards DJ, Dancorbo S. Routine monitoring of serum vancomycin concentrations: waiting for proof of its value. Clinical Pharmacy 6: 652–654, 1987

    PubMed  CAS  Google Scholar 

  • Evans NJ, Rutter N, Hadgraft J, Parr G. Percutaneous administration of theophylline in the preterm infant. Journal of Pediatrics 107: 307–311, 1985

    Article  PubMed  CAS  Google Scholar 

  • Fayed SB, Sutton AM, Turner TL, McAllister TA. The prophylactic use of ticarcillin/clavulanate in the neonate. Journal of Antimicrobial Chemotherapy 19: 113–118, 1987

    Article  PubMed  CAS  Google Scholar 

  • Freij BJ, McCracken GH, Olsen KD, Threlkeld N. Pharmacokinetics of imipenem-cilastatin in neonates. Antimicrobial Agents and Chemotherapy 27: 431–435, 1985

    Article  PubMed  CAS  Google Scholar 

  • Gibaldi M, Perrier D (Eds). Pharmacokinetics, 2nd ed., Marcel Dekker Inc., New York. 1982

    Google Scholar 

  • Glazer JP, Danish MA, Plotkin SA, Yaffe SJ. Disposition of chloramphenicol in low birth weight infants. Pediatrics 66: 573–578, 1980

    PubMed  CAS  Google Scholar 

  • Gouyon JB, Pechinot A, Safran C, Chretien S, Sandre D, et al. Pharmacokinetics of cefotaxime in preterm infants. Developmental Pharmacology and Therapeutics 14: 29–34, 1990

    PubMed  CAS  Google Scholar 

  • Granati B, Assael BM, Chung M, Montini C, Parini R, et al. Clinical pharmacology of netilmicin in preterm and term newborn infants. Journal of Pediatrics 106: 664–669, 1985

    Article  PubMed  CAS  Google Scholar 

  • Gross JR, Kaplan SL, Kramer WG, Mason EO. Vancomycin pharmacokinetics in premature infants. Pediatric Pharmacology 5: 17–22, 1985

    PubMed  CAS  Google Scholar 

  • Grossman M, Ticknor W. Serum levels of ampicillin, cephalothin, cloxacillin, and nafcillin in the newborn infant. Antimicrobial Agents and Chemotherapy: 214-219, 1966

  • Gruber WC, Rench MA, Garcia-Prats JA, Edwards MS, Baker CJ. Single-dose pharmacokinetics of imipenem-cilastatin in neonates. Antimicrobial Agents and Chemotherapy 27: 511–514, 1985

    Article  PubMed  CAS  Google Scholar 

  • Gulian J-M, Gonard V, Dalmasso C, Palix C. Bilirubin displacement by ceftriaxone in neonates: evaluation by determination of ‘free’ bilirubin and erythrocyte-bound bilirubin. Journal of Antimicrobial Chemotherapy 19: 823–829, 1987

    Article  PubMed  CAS  Google Scholar 

  • Hall P, Kaye CM, McIntosh N, Steele J. Intravenous metronidazole in the newborn. Archives of Disease in Childhood 58: 529–531, 1983

    Article  PubMed  CAS  Google Scholar 

  • Haughey DB, Hilligoss DM, Grassi A, Schentag JJ. Two-compartment gentamicin pharmacokinetics in premature neonates: a comparison to adults with decreased glomerular filtration rates. Journal of Pediatrics 96: 325–330, 1980

    Article  PubMed  CAS  Google Scholar 

  • Heimann G. Pharmacokinetics and clinical aspects of azlocillin in paediatrics. Journal of Antimicrobial Chemotherapy 11 (Suppl. B): 127–135, 1983

    Article  PubMed  Google Scholar 

  • Hindmarsh KW, Nation RL, Williams GL, John E, French JN. Pharmacokinetics of gentamicin in very low birth weight preterm infants. European Journal of Clinical Pharmacology 24: 649–653, 1983

    Article  PubMed  CAS  Google Scholar 

  • Howard JB, McCracken GH. Pharmacological evaluation of amikacin in neonates. Antimicrobial Agents and Chemotherapy 8: 86–90, 1975

    Article  PubMed  CAS  Google Scholar 

  • Howard JB, McCracken GH, Trujillo H, Mohs E. Amikacin in newborn infants: comparative pharmacology with kanamycin and clinical efficacy in 45 neonates with bacterial diseases. Antimicrobial Agents and Chemotherapy 10: 205–210, 1976

    Article  PubMed  CAS  Google Scholar 

  • Husson C, Chevalier JY, Jezequel M, Mathe JC, Costil J, et al. Pharmacokinetic study of gentamicin in preterm and term neonates. Developmental Pharmacology and Therapeutics 7 (Suppl. 1): 125–129, 1984

    PubMed  CAS  Google Scholar 

  • Jacobs RF, Kearns GL. Cefotaxime and desacetylcefotaxime in neonates and children: a review of microbiologic, pharmacokinetic, and clinical experience. Diagnostic Microbiology and Infectious Disease 12: 93–99, 1989

    Article  PubMed  CAS  Google Scholar 

  • Jager-Roman E, Doyle PE, Baird-Lambert J, Cvejic M, Buchanan N. Pharmacokinetics and tissue distribution of metronidazole in the newborn infant. Journal of Pediatrics 100: 651–654, 1982

    Article  PubMed  CAS  Google Scholar 

  • James A, Koren G, Milliken J, Soldin S, Prober C. Vancomycin pharmacokinetics and dose recommendations for preterm infants. Antimicrobial Agents and Chemotherapy 31: 52–54, 1987

    Article  PubMed  CAS  Google Scholar 

  • Janicke DM, Rubio TT, Wirth FH, Karotkin EH, Jusko WJ. Developmental pharmacokinetics of mezlocillin in newborn infants. Journal of Pediatrics 104: 773–781, 1984

    Article  PubMed  CAS  Google Scholar 

  • Jones RN, Barry AL, Thornsberry C. Antimicrobial activity of desacetylcefotaxime alone and in combination with cefotaxime: evidence of synergy. Reviews of Infectious Diseases 4 (Suppl.): S366–S373, 1982

    Article  PubMed  Google Scholar 

  • Jungbluth GL, Wirth FH, Rubio TT, Janicke DM, Jusko WJ. Developmental pharmacokinetics of mezlocillin in 4 newborn infants. Developmental Pharmacology and Therapeutics 11: 317–321, 1988

    PubMed  CAS  Google Scholar 

  • Kafetzis DA, Brater DC, Kapiki AN, Papas CV, Dellagrammaticus H, et al. Treatment of severe neonatal infections with cefotaxime. Efficacy and pharmacokinetics. Journal of Pediatrics 100: 483–489, 1982

    Article  PubMed  CAS  Google Scholar 

  • Kalenga M, Devos D, Moulin D, Verellen G. Bertrand JM. The need for pharmacokinetic monitoring of gentamicin therapy in critically ill neonates. Developmental Pharmacology and Therapeutics 7 (Suppl. 1): 130–133, 1984

    PubMed  Google Scholar 

  • Kaplan JM, McCracken GH. Clinical pharmacology of benzathine penicillin G in neonates with regard to its recommended use in congenital syphilis. Journal of Pediatrics 82: 1069–1072, 1973

    Article  Google Scholar 

  • Kaplan JM, McCracken GH, Horton LJ, Thomas ML, Davis N. Pharmacologic studies in neonates given large dosages of ampicillin. Journal of Pediatrics 84: 571–577, 1974

    Article  PubMed  CAS  Google Scholar 

  • Kaplan JM, McCracken GH, Thomas ML, Horton LJ, Davis N. Clinical pharmacology of tobramycin in newborns. American Journal of Diseases in Children 125: 656–660, 1973

    CAS  Google Scholar 

  • Kasik JW, Jenkins S, Leuschen MP, Nelson RM. Postconceptional age and gentamicin elimination half-life. Journal of Pediatrics 106: 502–505, 1985

    Article  PubMed  CAS  Google Scholar 

  • Kauffman RE, Miceli JN, Strebel L, Buckley JA, Done AK, et al. Pharmacokinetics of chloramphenicol and chloramphenicol succinate in infants and children. Journal of Pediatrics 98: 315–320, 1981

    Article  PubMed  CAS  Google Scholar 

  • Kearns GL, Bocchini JA, Brown RD, Cotter DL, Wilson JT. Absence of a pharmacokinetic interaction between chloramphenicol and acetaminophen in children. Journal of Pediatrics 107: 134–139, 1985

    Article  PubMed  CAS  Google Scholar 

  • Kearns GL, Jacobs RF, Thomas BR, Darville TL, Trang JM. Cefotaxime and desacetylcefotaxime pharmacokinetics in very low birth weight neonates. Journal of Pediatrics 114: 461–467, 1989

    Article  PubMed  CAS  Google Scholar 

  • Kenyon CF, Knoppert DC, Lee SK, Vandenberghe HM, Chance GW. Amikacin pharmacokinetics and suggested dosage modifications for the preterm infant. Antimicrobial Agents and Chemotherapy 34: 265–268, 1990

    Article  PubMed  CAS  Google Scholar 

  • Kildoo CW, Lin LM, Gabriel MH, Folli HL, Modanlou HD. Vancomycin pharmacokinetics in infants: relationship to post-conceptual age and serum creatinine. Developmental Pharmacology and Therapeutics 14: 77–83, 1990

    Google Scholar 

  • Kildoo C, Modanlou HD, Komatsu G, Harralson A, Hodding J. Developmental pattern of gentamicin kinetics in very low birth weight (VLBW) sick infants. Developmental Pharmacology and Therapeutics 7: 345–356, 1984

    PubMed  CAS  Google Scholar 

  • Koren G. Clinical pharmacology of antimicrobial drugs during development: are infants and children different? In Koren et al. (Eds) Antimicrobial therapy in infants and children, pp. 47–53, Marcel Dekker, Inc., New York, 1988

    Google Scholar 

  • 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. Clinical Pharmacology and Therapeutics 38: 680–685, 1985a

    Article  PubMed  CAS  Google Scholar 

  • Koren G, Leeder S, Harding E, Jacques D, MacLeod SM. Optimization of gentamicin therapy in very low birth weight infants. Pediatric Pharmacology 5: 79–87, 1985b

    PubMed  CAS  Google Scholar 

  • Koren G, Zarfin Y, Maresky D, Spiro TE, MacLeod SM. Pharmacokinetics of intravenous clindamycin in newborn infants. Pediatric Pharmacology 5: 287–292, 1986

    PubMed  CAS  Google Scholar 

  • Kuhn RJ, Nahata MC, Powell DA, Bickers RG. Pharmacokinetics of netilmicin in premature infants. European Journal of Clinical Pharmacology 29: 635–637, 1986

    Article  PubMed  CAS  Google Scholar 

  • Lanao JM, Dominguez-Gil A, Dominguez-Gil AA, Malaga S, Crespo M, et al. Modification in the pharmacokinetics of amikacin during development. European Journal of Clinical Pharmacology 23: 155–160, 1982

    Article  PubMed  CAS  Google Scholar 

  • 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. Developmental Pharmacology and Therapeutics 7: 285–302, 1984

    PubMed  CAS  Google Scholar 

  • Lee EL, Robinson MJ, Thong ML, Puthucheary SD. Rifamycin in neonatal flavobacteria meningitis. Archives of Disease in Childhood 51: 209–213, 1976

    Article  PubMed  CAS  Google Scholar 

  • Leonard MB, Koren G, Stevenson DK, Prober CG. Vancomycin pharmacokinetics in very low birth weight neonates. Pediatric Infectious Disease Journal 8: 282–286, 1989

    PubMed  CAS  Google Scholar 

  • Likitnukul S, McCracken GH, Threlkeld N, Darabi A, Olsen K. Pharmacokinetics and plasma bactericidal activity of aztreonam in low-birth-weight infants. Antimicrobial Agents and Chemotherapy 31: 81–83, 1987

    Article  PubMed  CAS  Google Scholar 

  • Lisby-Sutch SM, Nahata MC. Dosage guidelines for the use of vancomycin based on its pharmacokinetics in infants. European Journal of Clinical Pharmacology 35: 637–642, 1988

    Article  PubMed  CAS  Google Scholar 

  • Louvois J, James J, Mulhall A. Latamoxef and the newborn. Archives of Disease in Childhood 59: 346–350, 1984a

    Article  PubMed  Google Scholar 

  • Louvois J, Mulhall A, Hurley R. The safety and pharmacokinetics of cefotaxime in the treatment of neonates. Pediatric Pharmacology 2: 275–284, 1982a

    PubMed  Google Scholar 

  • Louvois J, Mulhall A, Hurley R. Cefuroxime in the treatment of neonates. Archives of Disease in Childhood 57: 59–62, 1982b

    PubMed  Google Scholar 

  • Louvois J, Mulhall A, James J. Moxalactam as an alternative to gentamicin in the treatment of clinically infected neonates. Developmental Pharmacology and Therapeutics 7 (Suppl. 1): 100–104, 1984b

    PubMed  Google Scholar 

  • Martin E, Koup JR, Paravicini U, Stoeckel K. Pharmacokinetics of ceftriaxone in neonates and infants with meningitis. Journal of Pediatrics 105: 475–481, 1984

    Article  PubMed  Google Scholar 

  • McCracken GH. Aminoglycoside toxicity in infants and children. American Journal of Medicine 80 (Suppl. 6B): 172–178, 1986

    Article  PubMed  Google Scholar 

  • McCracken GH, Ginsberg C, Chrane DF, Thomas ML, Horton LJ. Clinical pharmacology of penicillin in newborn infants. Journal of Pediatrics 82: 692–698, 1973

    Article  PubMed  Google Scholar 

  • McCracken GH, Kaplan JM. Penicillin treatment for congenital syphilis. Journal of the American Medical Association 228: 855–858, 1974

    Article  PubMed  Google Scholar 

  • McCracken GH, Mize SG, Threlkeld N. Intraventricular gentamicin therapy in Gram-negative bacillary meningitis of infancy. Lancet 1: 787–791, 1980

    PubMed  Google Scholar 

  • McCracken GH, Nelson JD (Eds). Antimicrobial therapy for newborns, Grune & Stratton, New York, 1983

    Google Scholar 

  • McCracken GH, Siegel JD, Threlkeld N, Thomas M. Ceftriaxone pharmacokinetics in newborn infants. Antimicrobial Agents and Chemotherapy 23: 341–343, 1983

    Article  PubMed  Google Scholar 

  • McCracken GH, Threlkeld N, Mize S, Baker CJ, Kaplan SL, et al. Moxalactam therapy for neonatal meningitis due to Gram-negative enteric bacilli. Journal of the American Medical Association 252: 1427–1432, 1984a

    Article  PubMed  Google Scholar 

  • McCracken GH, Threlkeld NE, Thomas ML. Pharmacokinetics of cefotaxime in newborn infants. Antimicrobial Agents and Chemotherapy 21: 683–684, 1982

    Article  PubMed  CAS  Google Scholar 

  • McCracken GH, Threlkeld N, Thomas ML. Pharmacokinetics of ceftazidime in newborn infants. Antimicrobial Agents and Chemotherapy 26: 583–584, 1984b

    Article  PubMed  CAS  Google Scholar 

  • McGee SM, Kaplan SL, Mason EO. Ventricular fluid concentrations of vancomycin in children after intravenous and intraventricular administration. Pediatric Infectious Disease Journal 9: 138–139, 1990

    Article  PubMed  CAS  Google Scholar 

  • Millar MR, Gorham P, Baxter H, Flannigan K, Congdon P. Pharmacokinetics of aztreonam in very low birthweight neonates. European Journal of Clinical Microbiology 6: 691–692, 1987

    Article  PubMed  CAS  Google Scholar 

  • Miranda JC, Schimmel MM, James LS, Spinelli W, Rosen TS. Gentamicin kinetics in the neonate. Pediatric Pharmacology 5: 57–61, 1985

    PubMed  CAS  Google Scholar 

  • Miranda JC, Schimmel MS, Mimms GM, Spinelli W, Driscoll JM, et al. Gentamicin absorption during prophylactic use for necrotizing enterocolitis. Developmental Pharmacology and Therapeutics 7: 303–306, 1984

    PubMed  CAS  Google Scholar 

  • Moore RD, Smith CR, Lietman PC. The association of aminoglycoside plasma level with therapeutic outcome in Gram-negative pneumonia. American Journal of Medicine 77: 657–662, 1984

    Article  PubMed  CAS  Google Scholar 

  • Morehead CD, Shelton S, Kusmiesz H, Nelson JD. Pharmacokinetics of carbenicillin in neonates of normal and low birth weight. Antimicrobial Agents and Chemotherapy 2: 267–271, 1972

    Article  PubMed  CAS  Google Scholar 

  • Mulhall A. Antibiotic treatment of neonates — does route of administration matter? Developmental Pharmacology and Therapeutics 8: 1–8, 1985

    PubMed  CAS  Google Scholar 

  • Mulhall A, Louvois J. The pharmacokinetics and safety of ceftazidime in the neonate. Journal of Antimicrobial Chemotherapy 15: 97–103, 1985

    Article  PubMed  CAS  Google Scholar 

  • Mulhall A, Louvois J, Hurley R. Incidence of potentially toxic concentrations of gentamicin in the neonate. Archives of Disease in Childhood 58: 897–900, 1983a

    Article  PubMed  CAS  Google Scholar 

  • Mulhall A. Louvois J, Hurley R. The pharmacokinetics of chloramphenicol in the neonate and young infant. Journal of Antimicrobial Chemotherapy 12: 629–639, 1983b

    Article  PubMed  CAS  Google Scholar 

  • Mulhall A, Louvois J, James J. Pharmacokinetics and safety of ceftriaxone in the neonate. European Journal of Pediatrics 144: 379–382, 1985

    Article  PubMed  CAS  Google Scholar 

  • Nahata MC. Lack of nephrotoxicity in pediatric patients receiving concurrent vancomycin and aminoglycoside therapy. Chemotherapy 33: 302–304, 1987a

    Article  PubMed  CAS  Google Scholar 

  • Nahata MC. Serum concentrations and adverse effects of chloramphenicol in pediatric patients. Chemotherapy 33: 322–327, 1987b

    Article  PubMed  CAS  Google Scholar 

  • Nahata MC, Durrell DE, Barson WJ. Moxalactam epimer kinetics in children. Clinical Pharmacology and Therapeutics 31: 528–532, 1982

    Article  PubMed  CAS  Google Scholar 

  • Nahata MC, Powell DA. Comparative bioavailability and pharmacokinetics of chloramphenicol after intravenous chloramphenicol succinate in premature infants and older patients. Developmental Pharmacology and Therapeutics 6: 23–32, 1983

    PubMed  CAS  Google Scholar 

  • Nahata MC, Powell DA, Durrell DE, Miller MA. Tobramycin pharmacokinetics in very low birth weight infants British Journal of Clinical Pharmacology 21: 325–327, 1986

    Article  PubMed  CAS  Google Scholar 

  • Nahata MC, Powell DA, Purrell DE, Miller MC, Glazer JP. Effect of gestational age and birth weight on tobramycin kinetics in newborn infants. Journal of Antimicrobial Chemotherapy 14: 59–65, 1984

    Article  PubMed  CAS  Google Scholar 

  • Nahata MC, Powell DA, Glazer JP, Hilty MD. Effect of intravenous flow rate and injection site on in vitro delivery of chloramphenicol succinate and in vivo kinetics. Journal of Pediatrics 99: 463–466, 1981

    Article  PubMed  CAS  Google Scholar 

  • Nahata MC, Powell DA, Gregoire RP, McClead RE, Menke JA, et al. Tobramycin kinetics in newborn infants. Journal of Pediatrics 103: 136–138, 1983

    Article  PubMed  CAS  Google Scholar 

  • Nakae S, Yamada M, Ito T, Chiba Y, Sasaki E, et al. Gentamicin dosing and pharmacokinetics in low birth weight infants. Tohoku Journal of Experimental Medicine 155: 213–223, 1988

    Article  PubMed  CAS  Google Scholar 

  • Naqvi SH, Keenan WJ, Reichley RM. Fortune KP. Vancomycin pharmacokinetics in small, seriously ill infants. American Journal of Diseases in Children 140: 107–110, 1986

    CAS  Google Scholar 

  • Naqvi SH, Maxwell MA, Dunkle LM. Cefotaxime therapy of neonatal Gram-negative bacillary meningitis. Pediatric Infectious Disease 4: 499–502, 1985

    Article  PubMed  CAS  Google Scholar 

  • Nelson JD (Ed.) Pocketbook of pediatric antimicrobial therapy, 8th ed., pp. 20–21, Williams & Wilkins, Baltimore, 1989

    Google Scholar 

  • Nelson JD, Kusmiesz H, Shelton S, Woodman E. Clinical pharmacology and efficacy of ticarcillin in infants and children. Pediatrics 61: 858–863, 1978

    PubMed  CAS  Google Scholar 

  • Nelson JD, McCracken GH. Clinical pharmacology of carbenicillin and gentamicin in the neonate and comparative efficacy with ampicillin and gentamicin. Pediatrics 52: 801–812, 1973

    PubMed  CAS  Google Scholar 

  • Nelson JD, Shelton S, Kusmiesz H. Clinical pharmacology of ticarcillin in the newborn infant: relation to age, gestational age, and weight. Journal of Pediatrics 87: 474–479, 1975

    Article  PubMed  CAS  Google Scholar 

  • O’Connor WJ, Warren GH, Edrada LS, Mandala PS, Rosenman SB. Serum concentrations of sodium nafcillin in infants during the perinatal period. Antimicrobial Agents and Chemotherapy 1965, pp. 220–222, 1966

    Google Scholar 

  • Odio C, Threlkeld N, Thomas ML, McCracken GH. Pharmacokinetic properties of mezlocillin in newborn infants. Antimicrobial Agents and Chemotherapy 25: 556–559, 1984

    Article  PubMed  CAS  Google Scholar 

  • Paap CM, Nahata MC. Clinical use of trimethoprim/sulfamethoxazole during renal dysfunction. DICP, The Annals of Pharmacotherapy 23: 646–654, 1989

    CAS  Google Scholar 

  • Patamasucon P, Kaojarern S, Kusmiesz H, Nelson JD. Pharmacokinetics of erythromycin ethylsuccinate and estolate in infants under 4 months of age. Antimicrobial Agents and Chemotherapy 19: 736–739, 1981

    Article  PubMed  CAS  Google Scholar 

  • Philips JB, Braune K, Ravis W, Cassady G, Dillon H. Pharmacokinetics of cefoperazone in newborn infants. Pediatric Pharmacology 4: 193–197, 1984

    PubMed  Google Scholar 

  • Phillips AMR, Milner RDG. Tissue concentrations of netilmicin and gentamicin in neonates. Journal of Infectious Diseases 149: 474, 1984

    Article  PubMed  CAS  Google Scholar 

  • Placzek M, Whitelaw A, Want S, Sahathevan M, Darrell J. Piperacillin in early neonatal infection. Archives of Disease in Childhood 58: 1006–1009, 1983

    Article  PubMed  CAS  Google Scholar 

  • Pons G, d’Athis P, Rey E, de Lauture D, Richard MO, et al. Gentamicin monitoring in neonates. Therapeutic Drug Monitoring 10: 421–427, 1988

    Article  PubMed  CAS  Google Scholar 

  • Powell DA, Nahata MC, Durrell DC. Interactions among chloramphenicol, phenytoin and phenobarbital in a pediatric patient. Journal of Pediatrics 98: 1001–1003, 1981

    Article  PubMed  CAS  Google Scholar 

  • Prinsloo JG, Delport SD, Moncrieff J, Paton AM. A preliminary pharmacokinetic study of ceftazidime in premature, newborn and small infants. Journal of Antimicrobial Chemotherapy 12 (Suppl. A): 361–364, 1983

    Article  PubMed  Google Scholar 

  • Prober CG. Effect of rifampin on chloramphenicol levels. New England Journal of Medicine 312: 788–789, 1985

    Article  PubMed  CAS  Google Scholar 

  • Prober CG, Stevenson DK, Benitz WE. The use of antibiotics in neonates weighing less than 1200 grams. Pediatric Infectious Disease Journal 9: 111–121, 1990

    Article  PubMed  CAS  Google Scholar 

  • Prober CG, Yeager AS, Arvin AM. The effect of chronologic age on the serum concentrations of amikacin in sick term and premature infants. Journal of Pediatrics 98: 636–640, 1981

    Article  PubMed  CAS  Google Scholar 

  • Rajchgot P, Prober C, Soldin S, Golas C, Good F, et al. Chloramphenicol pharmacokinetics in the newborn. Developmental Pharmacology and Therapeutics 6: 305–314, 1983

    PubMed  CAS  Google Scholar 

  • Reed MD, Aronoff SC, Myers CM, Husak MP, Bertino JS, et al. Developmental pharmacokinetics of moxalactam. Antimicrobial Agents and Chemotherapy 24: 383–387, 1983

    Article  PubMed  CAS  Google Scholar 

  • Reed MD, Kliegman RM, Weiner JS, Huang M, Yamashita TS, et al. The clinical pharmacology of vancomycin in seriously ill preterm infants. Pediatric Research 22: 360–363, 1987

    Article  PubMed  CAS  Google Scholar 

  • Reed MD, Myers CM, Yamashita TS, Blumer JL. Developmental pharmacology and therapeutics of piperacillin in Gram-negative infections. Developmental Pharmacology and Therapeutics 9: 102–114, 1986

    PubMed  CAS  Google Scholar 

  • Regazzi MB, Chirico G, Cristiani D, Rondini G, Rondanelli R. Cefoxitin in newborn infants: a clinical and pharmacokinetic study. European Journal of Clinical Pharmacology 25: 507–509, 1983

    Article  PubMed  CAS  Google Scholar 

  • Renlund M, Pettay O. Pharmacokinetics and clinical efficacy of cefuroxime in the newborn period. Proceedings of the Royal Society of Medicine 70 (Suppl. 9): 179–182, 1977

    PubMed  CAS  Google Scholar 

  • Ritter DA, Hansen TN, Speer ME, Kenny JD. Absorption of oral gentamicin in infants with necrotizing enterocolitis. In Nelson & Grassi (Eds) Current chemotherapy and infectious disease, Vol. II, pp. 1155–1157, American Society for Microbiology, Washington DC, 1980

    Google Scholar 

  • Roberts RJ. Intravenous administration of medication in pediatric patients: problems and solutions. Pediatric Clinics of North America 28: 23–34, 1981

    PubMed  CAS  Google Scholar 

  • Robertson A, Fink S, Karp W. Effect of cephalosporins on bilirubin-albumin binding. Journal of Pediatrics 112: 291–294, 1988

    Article  PubMed  CAS  Google Scholar 

  • Rodvold KA, Zokufa H, Rotschafer JC. Routine monitoring of serum vancomycin concentrations: can waiting be justified? Clinical Pharmacy 6: 655–658, 1987

    PubMed  CAS  Google Scholar 

  • Roos R, von Hattingberg HM, Belohradsky BH, Marget W. Pharmacokinetics of cefoxitin in premature and newborn infants studied by continuous serum level monitoring during combination therapy with penicillin and amikacin. Infection 8: 301–306, 1980

    Article  CAS  Google Scholar 

  • Rosenfeld WN, Evans HE, Batheja R, Jhaveri RC, Vohra K, et al. Pharmacokinetics of cefoperazone in full-term and premature neonates. Antimicrobial Agents and Chemotherapy 23: 866–869, 1983

    Article  PubMed  CAS  Google Scholar 

  • Rubio T, Wirth F, Karotkin E. Pharmacokinetic studies of mezlocillin in newborn infants. Journal of Antimicrobial Chemotherapy 9 (Suppl. A): 241–244, 1982

    Article  PubMed  Google Scholar 

  • Sardemann H, Colding H, Hendel J, Kampmann J, Hvidberg EF, et al. Kinetics and dose calculations of amikacin in the newborn. Clinical Pharmacology and Therapeutics 20: 59–66, 1976

    PubMed  CAS  Google Scholar 

  • Sarff LD, Deitch MW, Chiang ST. Nafcillin pharmacokinetics in neonates: dosage recommendation. In Nelson & Grassi (Eds) Current chemotherapy and infectious disease. Vol. 11, pp. 1154–1155, American Society for Microbiology, Washington DC, 1980

    Google Scholar 

  • Sarff LD, McCracken GH, Thomas ML, Horton LJ, Threlkeld N. Clinical pharmacology of methicillin in neonates. Journal of Pediatrics 90: 1005–1008, 1977

    Article  PubMed  CAS  Google Scholar 

  • Schaad UB, Hayton WL, Stoeckel K. Single-dose ceftriaxone kinetics in the newborn. Clinical Pharmacology and Therapeutics 37: 522–528, 1985

    Article  PubMed  CAS  Google Scholar 

  • Schaad UB, McCracken GH, Nelson JD. Clinical pharmacology and efficacy of vancomycin in pediatric patients. Journal of Pediatrics 96: 119–126, 1980

    Article  PubMed  CAS  Google Scholar 

  • Schaad UB, McCracken GH, Threlkeld N, Thomas ML. Clinical evaluation of a new broad-spectrum oxa-beta-lactam antibiotic, moxalactam, in neonates and infants. Journal of Pediatrics 98: 129–136, 1981

    Article  PubMed  CAS  Google Scholar 

  • Schaible DH, Rocci ML, Alpert GA, Campos JM, Paul MH, et al. Vancomycin pharmacokinetics in infants: relationships to indices of maturation. Pediatric Infectious Disease 5: 304–308, 1986

    Article  PubMed  CAS  Google Scholar 

  • Schentag JJ, Jusko WJ, Vance JW, Cumbo TJ, Abrutyn E, et al. Gentamicin disposition and tissue accumulation on multiple dosing. Journal of Pharmacokinetics and Biopharmacy 5: 559–577, 1977

    Article  CAS  Google Scholar 

  • Shankaran S, Kauffman RE. Use of chloramphenicol palmitate in neonates. Journal of Pediatrics 105: 113–115, 1984

    Article  PubMed  CAS  Google Scholar 

  • Siegel JD, McCracken GH, Thomas ML, Threlkeld N. Pharmacokinetic properties of netilmicin in newborn infants. Antimicrobial Agents and Chemotherapy 15: 246–253, 1979

    Article  PubMed  CAS  Google Scholar 

  • Sitka U, Weingartner L, Patsch R, Richter I. Pharmacokinetics of azlocillin in neonates. Chemotherapy 26: 171–176, 1980

    Article  PubMed  CAS  Google Scholar 

  • Speer ME, Mason EO, Scharnberg JT. Cerebrospinal fluid concentrations of aqueous procaine penicillin G in the neonate. Pediatrics 67: 387–388, 1981

    PubMed  CAS  Google Scholar 

  • Springer C, Eyal F, Michel J. Pharmacology of trimethoprim-sulfamethoxazole in newborn infants. Journal of Pediatrics 100: 647–650, 1982

    Article  PubMed  CAS  Google Scholar 

  • Steele RW, Eyre LB, Bradsher RW, Weinfeld RE, Patel IH, et al. Pharmacokinetics of ceftriaxone in pediatric patients with meningitis. Antimicrobial Agents and Chemotherapy 23: 191–194, 1983

    Article  PubMed  CAS  Google Scholar 

  • Stewart CF, Hampton EM. Effect of maturation on drug disposition in pediatric patients. Clinical Pharmacy 6: 548–564, 1987

    PubMed  CAS  Google Scholar 

  • St Gerne III JW, Polin RA. Neonatal sepsis. Progress in diagnosis and management. Drugs 36: 784–800, 1988

    Article  Google Scholar 

  • Stutman HR, Marks MI, Swabb EA. Single-dose pharmacokinetics of aztreonam in pediatric patients. Antimicrobial Agents and Chemotherapy 26: 196–199, 1984

    Article  PubMed  CAS  Google Scholar 

  • Stutman HR, Parker KM, Marks MI. Potential of moxalactam and other new antimicrobial agents for bilirubin-albumin displacement in neonates. Pediatrics 75: 294–298, 1985

    PubMed  CAS  Google Scholar 

  • Szefler SJ, Wynn RJ, Clarke DF, Buckwald S, Shen D, et al. Relationship of gentamicin serum concentrations to gestational age in preterm and term neonates. Journal of Pediatrics 97: 312–315, 1980

    Article  PubMed  CAS  Google Scholar 

  • Tarral E, Jehl F, Tarral A, Simeoni U, Monteil H, et al. Pharmacokinetics of teicoplanin in children. Journal of Antimicrobial Chemotherapy (Suppl. A): 47–51, 1988

    Article  Google Scholar 

  • Thirumoorthi MC, Dajani AS. Treatment of bacterial infections. Seminars in Perinatology 9: 38–46, 1985

    PubMed  CAS  Google Scholar 

  • Thomson AH, Way S, Bryson SM, McGovern EM, Kelman AW, et al. Population pharmacokinetics of gentamicin in neonates. Developmental Pharmacology and Therapeutics 11: 173–179, 1988

    PubMed  CAS  Google Scholar 

  • Trang JM, Jacobs RF, Kearns GL, Brown AL, Wells TG, et al. Cefotaxime and desacetylcefotaxime pharmacokinetics in infants and children with meningitis. Antimicrobial Agents and Chemotherapy 28: 791–795, 1985

    Article  PubMed  CAS  Google Scholar 

  • Watterberg KL, Kelly HW, Johnson JD, Aldrich M, Angelus P. Effect of patent ductus arteriosus on gentamicin pharmacokinetics in very low birth weight (< l,500g) babies. Developmental Pharmacology and Therapeutics 10: 107–117, 1987

    PubMed  CAS  Google Scholar 

  • Weiss CF, Glazko AJ, Weston JK. Chloramphenicol in the newborn infant. New England Journal of Medicine 262: 787–794, 1960

    Article  PubMed  CAS  Google Scholar 

  • Wilson CB, Koup JR. Clinical pharmacology of extended-spectrum penicillins in infants and children. Journal of Pediatrics 106: 1049–1056, 1985

    Article  PubMed  CAS  Google Scholar 

  • Windorfer A, Pringsheim W. Studies on the concentrations of chloramphenicol in the serum and cerebrospinal fluid of neonates, infants and small children. European Journal of Pediatrics 124: 129–138, 1977

    Article  PubMed  CAS  Google Scholar 

  • Wright PF, Kaiser AB, Bowman CM, McKee KT, Trujillo H, et al. The pharmacokinetics and efficacy of an aminoglycoside administered into the cerebral ventricles in neonates: implications for further evaluation of this route of therapy in meningitis. Journal of Infectious Diseases 143: 141–147, 1981

    Article  PubMed  CAS  Google Scholar 

  • Yogev R, Kolling WM. Intraventricular levels of amikacin after intravenous administration. Antimicrobial Agents and Chemotherapy 20: 583–586, 1981

    Article  PubMed  CAS  Google Scholar 

  • Yogev R, Williams T. Ventricular fluid levels of chloramphenicol in infants. Antimicrobial Agents and Chemotherapy 16: 7–8, 1979

    Article  PubMed  CAS  Google Scholar 

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  1. Colleges of Pharmacy and Medicine, Ohio State University, 500 West 12th Avenue, 150 Parks Hall, Columbus, Ohio, 43210, USA

    Christopher M. Paap &  Milap C. Nahata

  2. Columbus Children’s Hospital Wexner Institute for Pediatric Research, Columbus, Ohio, USA

    Christopher M. Paap &  Milap C. Nahata

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Paap, C.M., Nahata, M.C. Clinical Pharmacokinetics of Antibacterial Drugs in Neonates. Clin Pharmacokinet 19, 280–318 (1990). https://doi.org/10.2165/00003088-199019040-00003

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