Main Article Content
cystic fibrosis, multi-resistant bacterial infection, lactic acidosis, mitochondria, chloramphenicol
Children with cystic fibrosis are commonly colonized with multi-resistant bacteria. In such patients, infectious exacerbation may require salvage therapy with uncommonly used antimicrobials, including chloramphenicol. Chloramphenicol is rarely used nowadays because of the associated severe adverse events. We describe the case of a 15-year-old female with terminal cystic fibrosis who required intravenous (IV) chloramphenicol treatment for a Burkholderia cepacia ( B. cepacia ) exacerbation. The child subsequently developed lactic acidosis and secondary respiratory compensation adding to her baseline respiratory distress. Based on the Naranjo scale, the probability of chloramphenicol being the cause of the hyperlactatemia and associated respiratory distress was rated as probable, as the adverse effects resolved upon discontinuation of the drug. Subsequent genotyping for mitochondrial polymorphism (G3010A) confirmed a possible susceptibility to lactic acidosis from mitochondrial RNA-inhibiting agents such as chloramphenicol. Hyperlac - tatemia is a rare but life threatening adverse effect that has been previously reported with chloramphenicol exposure, but is not generally thought of. Clinicians should be aware of this potentially life threatening, but reversible adverse event. Lactate should be monitored under chloramphenicol and it should be discontinued as soon as this complication is suspected, especially in patients with low respiratory reserve.
2. Evans LS, Kleiman MB. Acidosis as a presenting feature of chloramphenicol toxicity. J Pediatr 1986;108(3):475–7.
3. Wiest DB, Cochran JB, Tecklenburg FW. Chloramphenicol toxicity revisited: a 12-year-old patient with a brain abcess. J Pediatr Pharmacol Ther 2012;17(2):182–8.
4. Duewelhenke N, Krut O, Eysel P. Influence on mitochondria and cytotoxicity of different antibiotics administered in high concentrations on primary human osteoblasts and cell lines. Antimicrob Agents Chemother 2007;51(1):54–63.
5. Riesbeck K, Bredberg A, Forsgren A. Ciprofloxacin does not inhibit mitochondrial functions but other antibiotics do. Antimicrob Agents Chemother1990 ; 34(1):167–9.
6. Kroon AM, Van den BC. Antibacterial drugs and their interference with the biogenesis of mitochondria in animal and human cells. Pharm Weekbl Sci1983; 5(3):81–7.
7. Del Pozo JL, Fernández-Ros N, Sáez E, et al. Linezolid-induced lactic acidosis in two liver transplant patients with the mitochondrial DNA A2706G polymorphism. Antimicrob Agents Chemother 2014;58(7):4227–9.
8. Palenzuela L, Hahn NM, Nelson RP, Jr., et al. Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis? Clin Infect Dis 2005;40(12):e113–6.
9. Su E, Crowley K, Carcillo J et al. Linezolid and lactic acidosis – A role for lactate monitoring with long-term linezolid use in children.Pediatr Infect Dis J 2011;30(9):804–6.
10. Carson J, Cerda J, Chae JH, et al. Severe lactic acidosis associated with linezolid use in a patient with the mitochondrial DNA A2706G polymorphism. Pharmacotherapy 2007;27(5):771–4.
11. Triton Pharma Inc. PR Septra ® Injection – Product Monograph. Concord, ON: Author; 2010. Available at: http://www.compagnonsdelatransplantation.ca/assets/ Product%20Monographs/Septra.PDF
12. Nordt SP, Vivero LE. Pharmaceutical additives. In: Hoff - man RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank’sToxicologic Emergencies, 10 th ed. New York, NY: McGraw-Hill; 2010. Available at: http://accesspharmacy.mhmedical.com/content.aspx?bookid =1163&Sectionid=65095471.
13. Naranjo CA, Busto U, Sellers EM et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30(2), 239–45.
14. The World Health Organization. Standardized treatment of bacterial meningitis in Africa in epidemic and non epidemic situations. Geneva: Author; 2007. Available at: http://www.who.int/csr/resources/publications/ meningitis/WHO_CDS_EPR_2007_3.pdf.
15. Long K, Vester B. Resistance to linezolid caused by modifications at its binding site on the ribosome. Antimicrob Agents Chemother 2012;56(2):603–12.
16. Plock N, Buerger C, Joukhadar, C et al. Does linezolid inhibit its own metabolism? – Population pharmacokinetics as a tool to explain the observed nonlinearity in both healthy volunteers and septic patients. Drug Metab Dispos 2007;35(10):1816–23.
17. Soriano A, Miro O, Mensa J. Mitochondrial toxicity associated with linezolid. N Engl J Med 2005;353(21):2305–6.
18. Flanagan S, McKee EE, Das D, et al. Nonclinical and pharmacokinetic assessments to evaluate the potential of tedizolid and linezolid to affect mitochondrial function. Antimicrob Agents Chemother 2015;59(1):178–85.
19. Kraut JA, Madias NE. Lacticacidosis. N Engl J Med 2014;371(24):2309–19.
20. Gunnerson KJ, Saul M, He S, et al. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care 2006;10(1):R22.
21. Nichol AD, Egi M, Pettila V, et al. Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study. Crit Care 2010;14(1):R25.
22. Okorie ON, Dellinger P. Lactate: biomarker and potential therapeutic target. Crit Care Clin 2011;27:299–26.