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Linezolid-induced hyperlactatemia in a burn patient
Annales Franc¸aises d’Anesthe´sie et de Re´animation 32 (2013) e117–e118
Letter to editor Linezolid-induced hyperlactatemia in a burn patient Hyperlactate´mie induite par le linezolid chez une patiente bruˆle´e Linezolid is an oxazolidinone antibiotic used for Gram-positive infections, especially those due to methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci [1]. It has been reported to induce lactic acidosis, especially after prolonged administration [2]. We report the case of a burn patient with severe hyperlactatemia concomitant to linezolid administration. A 90-year-old woman, without medical history, was admitted for 3rd degree burn injury of the right shoulder (burn skin surface: 1%). A skin graft was performed at day 1. At day 7, she developed a skin infection due to Staphylococcus epidermidis complicated by a sepsis. Because S. epidermidis is mainly methicillin-resistant despite methicillin-sensitive sub-population, a treatment with linezolid and gentamicin was instituted. Use of linezolid was justified by our fear of renal failure with the gold standard vancomycin [3]. At that time, renal function was normal with creatininemia at 54 mmol/L (MDRD = 98 mL/min). At day 11, hyperlactatemia occurred with values up to 8.1 mmol/ L (normal < 1.6 mmol/L). Despite this hyperlactatemia, pH was within normal values. Sepsis was immediately excluded in the absence of hyperthermia and state of shock. A trans-esophageal echography was negative for endocarditis. There was no liver insufficiency (prothrombin time = 76%, total bilirubin = 8.6 m-
mol/l [N = 1.7 and 17.1]). Thiamine deficiency was then suspected, but a treatment by thiamine did not correct hyperlactatemia. We then hypothesized linezolid-induced hyperlactatemia and this treatment was discontinued at day 20. During the following hours, lactatemia decreased drastically and was within normal values 2 days later (Fig. 1). Patient died of severe pneumonia at day 30. The most commonly reported adverse events associated with linezolid are gastrointestinal disturbances, myelopathy and optic neuropathy. Since 2003, 17 cases of linezolid-induced lactic acidosis have been reported [2]. Pathophysiology of this adverse event is thought to arise from mitochondrial toxicity by inhibition of protein synthesis. Indeed linezolid, a bacteriostatic antibiotic, inhibits bacterial growth by its fixation on bacterial 23S ribosomal RNA (rRNA) of the 50S subunit. This fixation prevents the formation of a functional 70S initiation complex. Linezolid may also inhibit mitochondrial 16S rRNA by a similar mechanism [4]. To date, no risk factor of linezolid-induced hyperlactatemia was clearly identified, but it seems that its occurrence is more frequent in patients with preexisting renal insufficiency or liver dysfunction. As illustrated in our case, hyperlactatemia appears rapidly reversible after drug withdrawal. Our case report has several interests. Firstly, it confirms rapid reversibility of this adverse event, even in elderly patients. Secondly, despite their renal safety, use of recent antibiotics has to be justified not only because of their consequences on unit bacterial ecology, but also because of their potential secondary adverse events.
Fig. 1. Evolution of lactatemia during hospitalization. Note hyperlactatemia starting 4 days after initiation of linezolid treatment and return to normal 2 days after the end of treatment. Normal value of lactatemia: less than 1.6 mmol/L. 0750-7658/$ – see front matter ß 2013 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Published by Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.annfar.2013.06.003
Letter to editor / Annales Franc¸aises d’Anesthe´sie et de Re´animation 32 (2013) e117–e118
However, linezolid seems to have some interest in burn center. Indeed, in France, linezolid is currently available for the treatment of skin and soft tissue infections, which are common complications in burn patient. Moreover, its efficacy seems to be superior to vancomycin in the treatment of complicated skin infections due to MRSA [5]. To conclude, although linezolid appears to be an excellent alternative to vancomycin in the treatment of skin and soft tissue infections, our case recalls that a few severe rare complications can occur and have to be searched. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Diekema DJ, Jones RN. Oxazolidinone antibiotics. Lancet 2001;358:1975–82.
[2] Apodaca AA, Rakita RM. Linezolid-induced lactic acidosis. N Engl J Med 2003;348:86–7. [3] Vance-Bryan K, Rotschafer JC, Gilliland SS, Rodvold KA, Fitzgerald CM, Guay DR. A comparative assessment of vancomycin-associated nephrotoxicity in the young versus the elderly hospitalized patient. J Antimicrob Chemother 1994;33:811–21. [4] Palenzuela L, Hahn N, Nelson R, Arno J, Schobert C, Bethel R, et al. Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis? Clin Infect Dis 2005;40:e113–6. [5] Weigelt J, Itani K, Stevens D, Lau W, Dryden M, Knirsch C, et al. Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother 2005;49:2260–6.
P. Esnault*, J. Cotte, P.-J. Cungi, P.-E. Romanat, H. Boret De´partement d’anesthe´sie-re´animation-bruˆle´s, HIA Sainte-Anne, 83000 Toulon, France *Corresponding author E-mail address: [email protected] (P. Esnault)
Letter to editor Linezolid-induced hyperlactatemia in a burn patient Hyperlactate´mie induite par le linezolid chez une patiente bruˆle´e Linezolid is an oxazolidinone antibiotic used for Gram-positive infections, especially those due to methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci [1]. It has been reported to induce lactic acidosis, especially after prolonged administration [2]. We report the case of a burn patient with severe hyperlactatemia concomitant to linezolid administration. A 90-year-old woman, without medical history, was admitted for 3rd degree burn injury of the right shoulder (burn skin surface: 1%). A skin graft was performed at day 1. At day 7, she developed a skin infection due to Staphylococcus epidermidis complicated by a sepsis. Because S. epidermidis is mainly methicillin-resistant despite methicillin-sensitive sub-population, a treatment with linezolid and gentamicin was instituted. Use of linezolid was justified by our fear of renal failure with the gold standard vancomycin [3]. At that time, renal function was normal with creatininemia at 54 mmol/L (MDRD = 98 mL/min). At day 11, hyperlactatemia occurred with values up to 8.1 mmol/ L (normal < 1.6 mmol/L). Despite this hyperlactatemia, pH was within normal values. Sepsis was immediately excluded in the absence of hyperthermia and state of shock. A trans-esophageal echography was negative for endocarditis. There was no liver insufficiency (prothrombin time = 76%, total bilirubin = 8.6 m-
mol/l [N = 1.7 and 17.1]). Thiamine deficiency was then suspected, but a treatment by thiamine did not correct hyperlactatemia. We then hypothesized linezolid-induced hyperlactatemia and this treatment was discontinued at day 20. During the following hours, lactatemia decreased drastically and was within normal values 2 days later (Fig. 1). Patient died of severe pneumonia at day 30. The most commonly reported adverse events associated with linezolid are gastrointestinal disturbances, myelopathy and optic neuropathy. Since 2003, 17 cases of linezolid-induced lactic acidosis have been reported [2]. Pathophysiology of this adverse event is thought to arise from mitochondrial toxicity by inhibition of protein synthesis. Indeed linezolid, a bacteriostatic antibiotic, inhibits bacterial growth by its fixation on bacterial 23S ribosomal RNA (rRNA) of the 50S subunit. This fixation prevents the formation of a functional 70S initiation complex. Linezolid may also inhibit mitochondrial 16S rRNA by a similar mechanism [4]. To date, no risk factor of linezolid-induced hyperlactatemia was clearly identified, but it seems that its occurrence is more frequent in patients with preexisting renal insufficiency or liver dysfunction. As illustrated in our case, hyperlactatemia appears rapidly reversible after drug withdrawal. Our case report has several interests. Firstly, it confirms rapid reversibility of this adverse event, even in elderly patients. Secondly, despite their renal safety, use of recent antibiotics has to be justified not only because of their consequences on unit bacterial ecology, but also because of their potential secondary adverse events.
Fig. 1. Evolution of lactatemia during hospitalization. Note hyperlactatemia starting 4 days after initiation of linezolid treatment and return to normal 2 days after the end of treatment. Normal value of lactatemia: less than 1.6 mmol/L. 0750-7658/$ – see front matter ß 2013 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Published by Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.annfar.2013.06.003
Letter to editor / Annales Franc¸aises d’Anesthe´sie et de Re´animation 32 (2013) e117–e118
However, linezolid seems to have some interest in burn center. Indeed, in France, linezolid is currently available for the treatment of skin and soft tissue infections, which are common complications in burn patient. Moreover, its efficacy seems to be superior to vancomycin in the treatment of complicated skin infections due to MRSA [5]. To conclude, although linezolid appears to be an excellent alternative to vancomycin in the treatment of skin and soft tissue infections, our case recalls that a few severe rare complications can occur and have to be searched. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Diekema DJ, Jones RN. Oxazolidinone antibiotics. Lancet 2001;358:1975–82.
[2] Apodaca AA, Rakita RM. Linezolid-induced lactic acidosis. N Engl J Med 2003;348:86–7. [3] Vance-Bryan K, Rotschafer JC, Gilliland SS, Rodvold KA, Fitzgerald CM, Guay DR. A comparative assessment of vancomycin-associated nephrotoxicity in the young versus the elderly hospitalized patient. J Antimicrob Chemother 1994;33:811–21. [4] Palenzuela L, Hahn N, Nelson R, Arno J, Schobert C, Bethel R, et al. Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis? Clin Infect Dis 2005;40:e113–6. [5] Weigelt J, Itani K, Stevens D, Lau W, Dryden M, Knirsch C, et al. Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother 2005;49:2260–6.
P. Esnault*, J. Cotte, P.-J. Cungi, P.-E. Romanat, H. Boret De´partement d’anesthe´sie-re´animation-bruˆle´s, HIA Sainte-Anne, 83000 Toulon, France *Corresponding author E-mail address: [email protected] (P. Esnault)