Advertisement

The Indian Journal of Pediatrics

, Volume 59, Issue 2, pp 213–219 | Cite as

Chloramphenicol clearance in typhoid fever: Implications for therapy

  • Zulfiqar A. Bhutta
  • Sarfaraz K. Niazi
  • Amin Suria
Original Articles

Abstract

We prospectively studied the pharmacokinetics of intravenous Chloramphenicol succinate (CS) in children (age 6 months-14 years) with culture proven typhoid fever (n=30) and non typhoidal illnesses (n=10). CS was administered in three different dosage regimens (50, 75 and 100 mg/kg/d-q 6 hourly). Liver function tests were monitored. Plasma trough and peak chloramphenicol concentrations were measured by HPLC analysis after 42 hrs. The 50 mg/kg/day dosage schedule was terminated midway through the study, as blood levels were consistently low and two patients with typhoid relapsed. children with typhoid has significantly lower clearance of CS in comparison with those with non-typhoidal illness (0.29±0.1 versus 0.5±0.37 1/kg/hr, P 0.05). There was no significant difference between mean peak and trough concentrations of chloramphenicol on 100 mg/kg/day and 75 mg/kg/day in children with typhoid. However, two children on 100 mg/kg/day dosage developed trough concentrations >20 mcg/ml. No correlation was found between CS clearance and serum bilirubin, SGPT (alanine transaminase) and alkaline phosphatase. Our data show altered clearance of CS in children with typhoid and suggests that 75 mg/kg/day may be a safer dose in children with hepatic dysfunction in typhoid.

Key Words

Chloramphenicol succinate (CS) Typhoid 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Pankey GA, Horton JM. Chloramphenicol. In: Ristucia AM, Cunha BA, Eds.Antimicrobial Therapy, New York: Taven Press, 1984: 249–253.Google Scholar
  2. 2.
    Smith AS, Weber A. Pharmacology of chloramphenicol.Pediatr Clin N Am 1983; 30: 209–236.Google Scholar
  3. 3.
    Pickering LK, Hoecker JL, Kramer WG et al. Clinical pharmacology of two chloramphenicol preparations in children: sodium succinate (IV) and palmitate (oral) esters.J Pediatr 1980; 96: 757–761.PubMedCrossRefGoogle Scholar
  4. 4.
    Leitman PS. Oral chloramphenicol therapy (editorial).J Pediatr 1981; 99: 905–960.CrossRefGoogle Scholar
  5. 5.
    Watson KB. Entric fevers. In: Jelliffe DB, Stanfield JP, Eds. Disease of Children in Tropics and Subtropics. Second edition, London: Edward Arnold, 1978; 692–669.Google Scholar
  6. 6.
    Feigin RD. Typhoid fever. In: Behrman RE, Vaughan VC, Eds. Nelson Textbook of Paediatrics. Thirteenth Edition, Tokyo: WB Saunders, 1987: 603–611.Google Scholar
  7. 7.
    Roy TE, Kreiger E, Craig G et al. Studies on the absorption of chloramphenicol in normal children in relation to the treatment of meningities.J Antimicrob Chemother 1952; 2: 505–512.Google Scholar
  8. 8.
    Kelly RS, Hunt AD Jr, Tashman SG. Studies on the absorption and distribution of chloramphenicol.Paediatrics 1951; 8: 362–368.Google Scholar
  9. 9.
    Scott JL, Finegold SM, Belkin GA et al. A controlled study of the hematologic toxicity of chloramphenicol.N Engl J Med 1965; 272: 1137–1141.PubMedCrossRefGoogle Scholar
  10. 10.
    Mulhall A, Louvois de J, Hurley R. The pharmacokinetics of chloramphenicol in the neonate and young infant.J Antimicrob Chemother 1933; 12: 629–639.CrossRefGoogle Scholar
  11. 11.
    Weiss CF, Glazko AJ, Weston JK. Chloramphenicol in the newborn infants.N Engl J Med 1960; 262: 787–795.PubMedCrossRefGoogle Scholar
  12. 12.
    Evans LS, Kleiman MB. Acidosis as a presenting feature of chloramphenicol toxicity.J Pediatr 1986; 108: 475–477.PubMedCrossRefGoogle Scholar
  13. 13.
    Wilkinson JD, Pollack MM, Costello J. Chloramphenicol toxicity: hemodynamic and oxygen utilization effects.Pediatr Infect Dis J 1985; 4: 69–71.Google Scholar
  14. 14.
    Kauffman RE, Thirumoorthi MC, Buckley JA et al. Relative bioavailability of intravenous chloramphenicol palmitate in infants and children.J Pediatr 1981; 99: 963–967.PubMedCrossRefGoogle Scholar
  15. 15.
    Meissner Cody H, Smith AL. The current Status of Chloramphenicol.Pediatrics 1979; 64: 348–355.Google Scholar
  16. 16.
    Azzollini F, Gazzaniga A, Lodola E, Natangelo R. elemination of chloramphenicol and thiamphenicol in subjects with cirrhosis of the liver.Int J Clin Pharmacol 1972; 62: 130–134.Google Scholar
  17. 17.
    Suhrland LG, Weisberger AS. Chloramphenicol toxicity in liver and renal disease.Arch Intern Med 1963; 112: 747–754.PubMedGoogle Scholar
  18. 18.
    Khosla SN, Singh R, Singh GP, Trehans VK. The spectrum of hepatic injury in exteric fever.Am J Gastroenterol 1988; 83: 413–416.PubMedGoogle Scholar
  19. 19.
    Ehle-Nilsson I, Kahlmeter G, Ehle-Nilsson P. Determination of chloramphenicol in serum and cerbrospinal fluid with high pressure liquid chromatography.J Antimicrob Chemother 1978; 4: 169–176.CrossRefGoogle Scholar
  20. 20.
    Sack CM, Koup JR, Smith AL. Chloramphenicol pharamacokinetics in infants and young children.Paediatric 1980; 66: 579–584.Google Scholar
  21. 21.
    Niazi SK. Pharmacokientic principles. In:Textbook of Biopharmaceutics and Clinical Pharmacokinetics. New York: Appleton Centry Crofts. 1979: 141.Google Scholar
  22. 22.
    Spika JS, Davis DJ, Martin SR et al. Interaction between chloramphenicol and acetaminophen.Arch Dis Child 1986; 61: 1121–1124.PubMedCrossRefGoogle Scholar
  23. 23.
    Ramachandran S, Godfrey JJ, Perera MVF. Typhoid hepatitis.JAMA 1974; 230: 236–240.PubMedCrossRefGoogle Scholar
  24. 24.
    Klotz SA, Jorgensen JH, Buckwold FJ, Craven PC. An epidemic with remarkably few clinical signs and symptoms.Arch Int Med 1984; 144: 544–537.CrossRefGoogle Scholar
  25. 25.
    Nolan JP. Bacteria and the liver.N Engl J Med 1978; 299: 1069–1071.PubMedCrossRefGoogle Scholar
  26. 26.
    Cava JJ, Guillermo MR. Salmonella antigens in the liver of patients with typhoid fever.J Infect Dis 1986; 154: 373–374.Google Scholar
  27. 27.
    Slaugher RL, Pieper JA, Cerra FB et al. Chloramphenicol sodium sucinate kinetics in critically ill patients.Clin Phamacol Ther 1980; 28: 69–77.CrossRefGoogle Scholar
  28. 28.
    Koup JP, Lay AH, Brodsky B, Slaughter RL. Chloramphenicol pharmacokinetics in hospitalized patients.Antimicrob Agents Chemother 1979; 15: 651–657.PubMedGoogle Scholar
  29. 29.
    Narang APS, Datta DV, Nath N, Mathur VS. Pharmacokinetic study of chloramphenicol in patients with liver Disease.Eur J Clin Pharmacol 1981; 20: 479–483.PubMedCrossRefGoogle Scholar
  30. 30.
    Kauffman RE, Miceli JN, Strebel L et al. of chloramphenicol and chloramphenicol succinate in infants and children.Pediatr Pharmacol Therap 1981; 98: 315–320.Google Scholar
  31. 31.
    Friedman CA, Lovejoy FC, Smith AL. Chloramphenicol disposition in infants and children.Pediatrics 1979; 95: 1071–1077.CrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 1992

Authors and Affiliations

  • Zulfiqar A. Bhutta
    • 1
  • Sarfaraz K. Niazi
    • 1
  • Amin Suria
    • 1
  1. 1.Department of Pediatrics and Pharmacology, Faculty of Health SciencesThe Aga Khan UniversityKarachiPakistan

Personalised recommendations