Summary
Cefotaxime is a third generation cephalosporin antimicrobial agent which has received wide acceptance as a first-line antibiotic for many infections in neonates, infants and children. With an average elimination half-life of about 1h, cefotaxime is not considered to be a ‘long half-life cephalosporin’ like ceftriaxone. For this reason, currently accepted dosage regimens for cefotaxime in infants and children employ a dosage of 50 mg/kg every 6h.
Re-examination of the paediatric pharmacokinetic data for cefotaxime and use of simple multiple-dose pharmacokinetic simulation of alternative dosage regimens was performed. From this analysis, regimens administering 75 mg/kg of the drug every 8h or every 12h were projected to produce serum cefotaxime concentrations adequate to effectively kill many of the common pathogens against which the drug is currently indicated for use in children. The clinical utility of these alternative dosage regimens was supported by a review of the medical literature and examination of the clinical results from studies in neonates, infants and children where cefotaxime was administered in 2 to 3 divided doses daily. It would appear, therefore, that increasing the cefotaxime dosage to 75 mg/kg administered at 8h intervals would result in less frequent drug administration which would not be expected to compromise safety and efficacy. Alternative dosage regimens for cefotaxime merit further consideration and clinical evaluation before they become commonly used in paediatric therapeutics.
Similar content being viewed by others
References
Andriono T, Susanta I, Makmuri M, Santosa G. Acute mediastinitis. Paediatrica Indonesiana 29: 116–120, 1989
Aufrant C, Lambert-Zechovsky N, Aujard Y, Bingin E, Blum C, et al. Cefotaxime and Gram-negative infections in children: effectiveness and tolerance. Nouvelle Presse Medicale 10: 639–646, 1981
Badelon O, Bingen E, Sauzeau C, Lambert-Zechovsky N, Ribier A, et al. First line antibiotic treatment in bone and joint sepsis in children. Pathologie Biologie 36: 746–749, 1988
Baird-Lambert J, Doyle PE, Thomas D, Cvejic M, Buchanan N. Pharmacokinetics of cefotaxime in neonates. Journal of Antimicrobial Chemotherapy 13: 471–477, 1984
Bingen E, Lambert-Zechovsky N, Aujard Y, Blondin G, Mariani P, et al. Beta-lactamase activity in bronchial sputum and treatment failure against penicillin-sensitive bacteria in pulmonary infections. Journal of Antimicrobial Chemotherapy 24: 622–624, 1989
Blumer JL, Stern RC, Yamashita TS, Myers CM, Reed MD. Cephalosporin therapeutics in cystic fibrosis. Journal of Pediatrics 108: 854–860, 1986
Cho N, Fukunaga K, Kuni K. A study of clinical application of cefotaxime in perinatal period. Japanese Journal of Antibiotics 35: 1855–1876, 1982
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
De Louvois J, Mulhall A, Hurley R. The safety and pharmacokinetics of cefotaxime in the treatment of neonates. Pediatric Pharmacology 2: 275–284, 1983
Doraiswamy B, Hammerschlag MR, Pringle GF, Du Bouchet L. Ophthalmia neonatorum caused by β-lactamase-producing Neisseria gonorrhoeae. Journal of the American Medical Association 250: 790–791, 1983
Feldstein TJ, Uden DL, Larson TA. Cefotaxime for treatment of Gram-negative bacterial meningitis in infants and children. Pediatric Infectious Disease Journal 6: 471–475, 1987
Fraise AP, Meeks ACG, Richards JE. Meningitis due to Haemophilus influenzae resistant to ampicillin and chloramphenicol. Archives of Disease in Childhood 61: 1134–1135, 1986
Friis H. Antibacterial activity of cefotaxime, desacetylcefotaxime and the combination of the two. Diagnostic Microbiology and Infectious Diseases 12: 67–72, 1989
Garnier JM, Giraud F. Cefotaxime in childhood infections. Nouvelle Presse Medicale 10: 629–633, 1981
Gekle D, Rangoonwala R, Seeger K. Clinical and kinetic studies on cefotaxime in the treatment of bacterial infections in children. Infection 8 (Suppl. 4): S509–S512, 1980
Gouyon JB, Duez JM, Portier H, Brichon P, Kohli E, et al. The fosfomycin-cefotaxime combination in severe staphylococcal infections in neonates. Presse Medicale 14: 2135–2138, 1985
Haffejee IE. Cefotaxime versus penicillin-chloramphenicol in purulent meningitis: a controlled single-blind clinical trial. Annals of Tropical Paediatrics 8: 225–229, 1988
Haffejee IE. A therapeutic trial of cefotaxime versus penicillin-gentamicin for severe infections in children. Journal of Antimicrobial Chemotherapy 14 (Suppl. B): 147–152, 1984
Hall MA, Ducker DA, Lowes JA, McMichael J, Clarke P, et al. A randomised prospective comparison of cefotaxime versus netilmicin/penicillin for treatment of suspected neonatal sepsis. Drugs 35 (Suppl. 2): 169–177, 1988
Hall MA, Beech RC, Seal DV. The use of cefotaxime for treating suspected neonatal sepsis: 2 years’ experience. Journal of Hospital Infection 8: 57–63, 1986
Hashira S, Koike Y, Fujii R. Fundamental and clinical investigations of cefotaxime in neonates. Japanese Journal of Antibiotics 35: 1737–1748, 1982
Helwig H, Schlegel P. Cefotaxime monotherapy in bacterial meningitis of childhood. Monatsschrift für Kinderheilkunde 134: 733–737, 1986
Helwig H, Nelson JD, Grassi C. Cefotaxime in pediatrics. In Nelson & Grassi (Eds) Current chemotherapy of infectious disease: Proceedings of the 11th ICC and 19th ICAAC, pp. 128–129, American Society of Microbiology, Boston, Oct 1–5, 1979
Helwig H. Experience with cefotaxime in children. Infection 8 (Suppl. 4): S506–S508, 1980
Helwig HF. Cefotaxime in pediatrics. In Abstracts of the 11th ICC and 19th ICAAC, American Society of Microbiology, Boston, Oct 1–5, 1979
Hervas JA, Ciria L, Henales V, Lopez P, De La Fuente A, et al. Nonsurgical management of neonatal multiple brain abscesses due to Proteus mirabilis. Helvetica Paediatrica Acta 42: 451–456, 1987
Ichioka T, Miyao M. Clinical experience with cefotaxime in bacterial infections of children. Chemotherapy 28 (Suppl. 1): 556–559, 1980
Ings RMJ, Fillastre JP, Godin M, Leroy A, Humbert G. The pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired renal function. Reviews of Infectious Diseases 4 (Suppl.): S366–373, 1982
Iwai N, Sasaki A, Taneda Y, Mizoguchi F, Nakamura H. Study on use of cefotaxime in neonates. Japanese Journal of Antibiotics 35: 1783–1792, 1982
Jacobs RF. Cefotaxime treatment of Gram-negative enteric meningitis in infants and children. Drugs 35 (Suppl. 2): 185–189, 1988
Jacobs RF, Kearns GL. Cefotaxime and desacetylcefotaxime in neonates and children: a review of microbiologic, pharmacokinetic and clinical experience. Diagnostic Microbiology and Infectious Diseases 12: 93–99, 1989
Kafetzis DA, Brater DG, Kanarios J, Sinaniotis CA, Papadatos CJ. Clinical pharmacology of cefotaxime in pediatric patients. Antimicrobial Agents and Chemotherapy 20: 487–490, 1981
Kafetzis DA, Brater DG, Kapiki AN, Papas CV, Dellagrammaticas H, et al. Treatment of severe neonatal infections with cefotaxime: efficacy and pharmacokinetics. Journal of Pediatrics 100: 483–489, 1982
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
Kearns GL, Reed MD. Clinical pharmacokinetics in infants and children: a reappraisal. Clinical Pharmacokinetics 17 (Suppl. 1): 29–67, 1989
Lecour H, Seara A, Cordeiro J, Miranda M. Treatment of childhood bacterial meningitis. Infection 17: 343–346, 1989
Lolekha S, Poojenapun A. Cefotaxime in serious and antibiotic-resistant infections in children. Journal of the Medical Association of Thailand 67: 392–396, 1984
Marget W, Belohradsky B, Roos R. Effect of revised drug schedules with the cephalosporine HR756 on the treatment of severe infections. Abstract A296. In Abstracts of the 18th ICAAC, American Society for Microbiology, Atlanta, October, 1978
Marquardt DW. An algorithm for least-squares estimation of nonlinear parameters. Journal of the Society of Industrial and Applied Mathematics 11: 431–441, 1963
McCracken GH Jr, Threlkeld NE, Thomas ML. Pharmacokinetics of cefotaxime in newborn infants. Antimicrobial Agents and Chemotherapy 21: 683–684, 1982
Morselli PL. Clinical pharmacology of the perinatal period and early infancy. Clinical Pharmacokinetics 17 (Suppl. 1): 13–28, 1989
Nakazawa S, Sato H, Suzuki H, Iwasaki A, Niino K, et al. Cefotaxime in pediatrics: basic and clinical studies. Chemotherapy 28 (Suppl. 1): 468–478, 1980
Nanri S, Akita H, Jozaki K, Iwata S, Twasaki Y, et al. Fundamental and clinical studies of cefotaxime in neonates and immature infants. Japanese Journal of Antibiotics 35: 1749–1760, 1982
Nishibayashi Y, Hamawaki M, Ozaki H, Kitamura I. The therapeutic effects of cefotaxime on various infectious diseases in children. Chemotherapy 28 (Suppl. 1): 560–569, 1980
Odio CM, Faingezicht I, Mohs E, Salas JL, McCracken GH. Cefotaxime (CTX) versus conventional therapy for bacterial meningitis in infants and children. Abstract 132. In Abstracts of the 24th ICAAC, American Society for Microbiology, Washington, DC, October 8–10, 1984
Ohkawa M, Okasho A, Motoi I, Togunaga S, Shoda R, et al. Elimination kinetics of cefotaxime and desacetylcefotaxime in patients with renal insufficiency and during hemodialysis. Chemotherapy 29: 4–12, 1983
Oran O, Yurdakok M, Tekinalp G, Kanra G. Cefotaxime and amikacin combination in the treatment of salmonella infection in premature infants. Turkish Journal of Pediatrics 30: 247–252, 1988
Papadatos CJ, Kafetzis DA, Kanarios J. Cefotaxime in the treatment of severe paediatric infections. Journal of Antimicrobial Chemotherapy 6 (Suppl. A): 243–248, 1980
Peters HH, Tillmann W, Schroeter W. Clinical experience with cefotaxime in anti-infection therapy of children treated with cytotoxic drugs. Infection 8(Supp. 4): S513–S515, 1980
Pils P, Schmidt P, Zazgornik J, Graninger W, Kopsa H, et al. Azlocillin and HR 756 in urosepsis and urinary tract infections with multiresistant Pseudomonas and Proteus morganii. Deutsche Medizinische Wochenschrift 104: 66–67, 1979
Porras-Ramirez G, Mendez Calderon E, Garcia Fernandeaz J, Animas Astorga S. Clinical trial of cefotaxime in severe pediatric infections. Investagación Medica Internacional 9: 51–61, 1982
Reynolds V, Oates jk, Newsom SWB. Prepubertal gonococcal vulvovaginitis: a penicillin-resistant infection treated with cefotaxime. Lancet 2: 206–207, 1979
Roos R, Marget W, Trujillo H, Kafetzis DA, Papadatos CJ, et al. Multicenter study on cefotaxime in meningitis and septicemia in children: clinica;l results, serum pharmacokinetics and concentrations in cerebrospinal fluid. Infection 8 (Suppl. 4): S501–S505, 1980
Rosch W, Welte WA, Clinical experiences with cefotaxim in pediatric surgery. Medizinische Welt 40: 149–153, 1989
Rusconi F, Rancilio L, Cerri MA, Parizzi F, Pietrogrande MC, et al. Cefotaxime in the treatment of severe bacterial pneumonia in paediatric patients. Drugs 35 (Suppl. 2): 203–204, 1988
Scheifele DW, Ginter GL, Olsen E, Fussell S, Pendray M. Comparison of two antibiotic regimens for neonatal necrotizing enterocolitis. Journal of Antimicrobial Chemotherapy 20: 421–429, 1987
Sow A. Cefotaxime treatment of meningitis in children. Journal of Antimicrobial Chemotherapy 14 (Suppl. B): 191–194, 1984
Steele RW. Ceftriaxone: increasing the half-life and activity of the third generation cephalosporins. Pediatric Infectious Diseases Journal 4: 188–191, 1985
Steele RW, Eyre LB, Bradsher RW, et al. Pharmacokinetics of ceftriaxone in pediatric patients with meningitis. Antimicrobial Agents and Chemotherapy 23: 191–194, 1983
Steele RW, Kearns GL. Antimicrobial therapy for pediatric patients. Pediatric Clinics of North America 36: 1321–1349, 1989
Stevens DL, Bergstrom R, Gibbons A. Synergistic interaction of cefotaxime and its metabolite desacetylcefotaxime demonstrated by drug-impregnated disks. Diagnostic Microbiology and Infectious Diseases 12: 73–80, 1989
Toyonaga Y, Kurosu Y, Sugita M, Hori M. Basic and clinical studies on use of cefotaxime in neonates. Japanese Journal of Antibiotics 35: 1767–1782, 1982
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
Varghese M, Khan AJ, Kumar K, Schaeffer HA, Pierro M, et al. Evaluation of cefotaxime in bacterial infections. Clinical Pediatrics 23: 220–222, 1984
Vogelman B, Craig WA. Kinetics of antimicrobial activity. Journal of Pediatrics 108: 835–840, 1986
von Loewenich V, Miething R, Uihlein M, Knothe M, Greipel-Zamorski M. Cefotaxime and deacetyl-cefotaxime in cerebrospinal fluid of newborn and premature infants. Pediatrie und Padologie 18: 361–366, 1983
Weber SA, Tuohy P. Bacteroides fragilis meningitis in a premature infant successfully treated with metronidazole. Pediatric Infectious Disease Journal 7: 886–887, 1988
Wise R, Wright N, Wills PJ. Pharmacology of cefotaxime and its desacetyl metabolite in renal and hepatic disease. Antimicrobial Agents and Chemotherapy 19: 526–531, 1981
Yamaoka K, Nakagawa T, Uno T. Application of Akaike’s information criterion (AIC) in the evaluation of linear pharmacokinetic equations. Journal of Pharmacokinetics and Biopharmaceutics 6: 165175, 1978
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kearns, G.L., Young, R.A. & Jacobs, R.F. Cefotaxime Dosage in Infants and Children. Clin. Pharmacokinet. 22, 284–297 (1992). https://doi.org/10.2165/00003088-199222040-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199222040-00004