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Comparative analysis of lactic acidosis induced by linezolid and vancomycin therapy using cohort and case–control studies of incidence and associated risk factors

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Abstract

Purpose

Lactic acidosis is a rare complication of linezolid (LZD) therapy, and its incidence and risk factors remain unknown. This study aimed to compare the incidence of LZD-associated lactic acidosis (LALA) and vancomycin (VAN)-associated lactic acidosis (VALA) and investigate the risk factors for LALA.

Methods

We performed a retrospective cohort study using propensity score-matched analyses comparing the incidence of lactic acidosis between LZD and VAN therapy. We included adult patients administered LZD or VAN between April 2014 and March 2016 and extracted patient baseline data. In a case–control study, we identified the risk factors of lactic acidosis in patients treated with LZD.

Results

We identified 94 and 313 patients who were administered LZD and VAN, respectively. The incidence of lactic acidosis after LZD and VAN therapy was 10.6 and 0.3%, respectively. After propensity score-matched analyses, the incidence of lactic acidosis with LZD therapy was significantly higher than that with VAN therapy [10.0% (8/80) vs. 0% (0/80), respectively; risk difference, 0.1; 95% confidence interval (CI), 0.03–0.17; p = 0.004]. In a case–control study, 10 patients with LALA were matched to 20 non-lactic acidosis patients by age and sex. Patients with LALA were more likely to have renal insufficiency than non-lactic acidosis patients that were in the univariate analysis (odds ratio, 7.4; 95% CI, 1.0–84.4; p = 0.02).

Conclusions

This study indicates that LALA occurs more frequently than VALA does and is associated with renal insufficiency. Therefore, close monitoring of kidney function and serum lactate is recommended during LZD therapy.

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References

  1. Sazdanovic P, Jankovic SM, Kostic M, Dimitrijevic A, Stefanovic S (2016) Pharmacokinetics of linezolid in critically ill patients. Expert Opin Drug Metab Toxicol 12(6):595–600. https://doi.org/10.1517/17425255.2016.1170807

    Article  CAS  PubMed  Google Scholar 

  2. Narita M, Tsuji BT, Yu VL (2007) Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy 27(8):1189–1197. https://doi.org/10.1592/phco.27.8.1189

    Article  CAS  PubMed  Google Scholar 

  3. Apodaca AA, Rakita RM (2003) Linezolid-induced lactic acidosis. N Engl J Med 348(1):86–87. https://doi.org/10.1056/NEJM200301023480123

    Article  PubMed  Google Scholar 

  4. Im JH, Baek JH, Kwon HY, Lee J-S (2015) Incidence and risk factors of linezolid-induced lactic acidosis. Int J Infect Dis 31:47–52. https://doi.org/10.1016/j.ijid.2014.12.009

    Article  CAS  PubMed  Google Scholar 

  5. Beekmann SE, Gilbert DN, Polgreen PM (2008) Toxicity of extended courses of linezolid: results of an Infectious Diseases Society of America Emerging Infections Network survey. Diagn Microbiol Infect Dis 62(4):407–410. https://doi.org/10.1016/j.diagmicrobio.2008.08.009

    Article  CAS  PubMed  Google Scholar 

  6. Huang W, Castelino RL, Peterson GM (2016) Lactic acidosis and the relationship with metformin usage: case reports. Medicine 95(46):e4998. https://doi.org/10.1097/MD.0000000000004998

    Article  PubMed  PubMed Central  Google Scholar 

  7. Palenzuela L, Hahn NM, Nelson RP et al (2005) Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis? Clin Infect Dis 40(12):e113–e116. https://doi.org/10.1086/430441

    Article  PubMed  Google Scholar 

  8. Soriano A, Miró O, Mensa J (2005) Mitochondrial toxicity associated with linezolid. N Engl J Med 353(21):2305–2306. https://doi.org/10.1056/NEJM200511243532123

    Article  CAS  PubMed  Google Scholar 

  9. Sujata LM, Russell GB, Hire D, Cardona C, Bleyer AJ (2009) Lactic acidosis from linezolid in a hospitalized patient with kidney failure. Infect Dis Clin Prac 17(6):404–406. https://doi.org/10.1097/IPC.0b013e31819b8bf4

    Article  Google Scholar 

  10. Wiener M, Guo Y, Patel G, Fries BC (2007) Lactic acidosis after treatment with linezolid. Infection 35(4):278–281. https://doi.org/10.1007/s15010-007-6302-x

    Article  CAS  PubMed  Google Scholar 

  11. Lee YR, Powell N, Bonatti H, Sawyer RG, Barroso L, Pruett TL, Sifri CD, Volles D (2008) Early development of lactic acidosis with short term linezolid treatment in a renal recipient. J Chemother 20(6):766–767. https://doi.org/10.1179/joc.2008.20.6.766

    Article  CAS  PubMed  Google Scholar 

  12. Contou D, Fichet J, Grimaldi D, Cariou A (2011) Early life-threatening lactic acidosis following a single infusion of linezolid. Int J Antimicrob Agents 38(1):84–85. https://doi.org/10.1016/j.ijantimicag.2011.01.025

    Article  CAS  PubMed  Google Scholar 

  13. Velez JCQ, Janech MG (2010) A case of lactic acidosis induced by linezolid. Nat Rev Nephrol 6(4):236–242. https://doi.org/10.1038/nrneph.2010.20

    Article  PubMed  Google Scholar 

  14. Garrabou G, Soriano A, López S et al (2007) Reversible inhibition of mitochondrial protein synthesis during linezolid-related hyperlactatemia. Antimicrob Agents Chemother 51(3):962–967. https://doi.org/10.1128/AAC.01190-06

    Article  CAS  PubMed  Google Scholar 

  15. Del Pozo JL, Fernandez-Ros N, Saez E, Herrero JI, Yuste JR, Banales JM (2014) Linezolid-induced lactic acidosis in two liver transplant patients with the mitochondrial DNA A2706G polymorphism. Antimicrob Agents Chemother 58(7):4227–4229. https://doi.org/10.1128/AAC.02856-14

    Article  PubMed  PubMed Central  Google Scholar 

  16. Carson J, Cerda J, Chae J-H, Hirano M, Maggiore P (2007) Severe lactic acidosis associated with linezolid use in a patient with the mitochondrial DNA A2706G polymorphism. Pharmacotherapy 27(5):771–774. https://doi.org/10.1592/phco.27.5.771

    Article  CAS  PubMed  Google Scholar 

  17. Tanaka M, Takeyasu T, Fuku N (2004) Mitochondrial genome single nucleotide polymorphisms and their phenotypes in the Japanese. Ann N Y Acad Sci 1011(1):7–20. https://doi.org/10.1196/annals.1293.002

    Article  CAS  PubMed  Google Scholar 

  18. Tanaka M, Cabrera VM, González AM, Larruga JM, Takeyasu T, Fuku N, Guo LJ, Hirose R, Fujita Y, Kurata M, Shinoda K, Umetsu K, Yamada Y, Oshida Y, Sato Y, Hattori N, Mizuno Y, Arai Y, Hirose N, Ohta S, Ogawa O, Tanaka Y, Kawamori R, Shamoto-Nagai M, Maruyama W, Shimokata H, Suzuki R, Shimodaira H (2004) Mitochondrial genome variation in eastern Asia and the peopling of Japan. Genome Res 14(10a):1832–1850. https://doi.org/10.1101/gr.2286304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Song T, Lee M, Jeon H-S et al (2015) Linezolid trough concentrations correlate with mitochondrial toxicity-related adverse events in the treatment of chronic extensively drug-resistant tuberculosis. EBioMedicine 2(11):1627–1633. https://doi.org/10.1016/j.ebiom.2015.09.051

    Article  PubMed  PubMed Central  Google Scholar 

  20. Palanichamy MG, Sun C, Agrawal S et al (2003) Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia. Am J Hum Genet 75:966–978

    Article  Google Scholar 

  21. Achilli A, Rengo C, Magri C, Battaglia V, Olivieri A, Scozzari R, Cruciani F, Zeviani M, Briem E, Carelli V, Moral P, Dugoujon JM, Roostalu U, Kivisild T, Bandelt HJ, Richards M, Villems R, Santachiara-Benerecetti AS, Semino O, Torroni A (2004) The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool. Am J Hum Genet 75(5):910–918. https://doi.org/10.1086/425590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Matsumoto K, Takeshita A, Ikawa K, Shigemi A, Yaji K, Shimodozono Y, Morikawa N, Takeda Y, Yamada K (2010) Higher linezolid exposure and higher frequency of thrombocytopenia in patients with renal dysfunction. Int J Antimicrobial Agents 36(2):179–181. https://doi.org/10.1016/j.ijantimicag.2010.02.019

    Article  CAS  Google Scholar 

  23. Nukui Y, Hatakeyama S, Okamoto K, Yamamoto T, Hisaka A, Suzuki H, Yata N, Yotsuyanagi H, Moriya K (2013) High plasma linezolid concentration and impaired renal function affect development of linezolid-induced thrombocytopenia. J Antimicrob Chemother 68(9):2128–2133. https://doi.org/10.1093/jac/dkt133

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Editage (www.editage.com) for the English language editing and Publication Support.

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Authors and Affiliations

Authors

Contributions

NM, YK, and SB contributed to conception and design of the study. All authors contributed to acquisition of data and data analysis. NM mainly contributed to drafting this article. All authors contributed to the critical revision and gave final approval of the manuscript.

Corresponding author

Correspondence to Nobuaki Mori.

Ethics declarations

This study was approved by the NTMC ethics committee (IRB protocol number: R16-102) and was carried out in accordance with the Declaration of Helsinki principles. The need for patient consent was waived owing to the retrospective nature of the study. Information about the study was made public through postings on facility notice boards and webpages. Patients and their representative agents had the right to refuse study participation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Mori, N., Kamimura, Y., Kimura, Y. et al. Comparative analysis of lactic acidosis induced by linezolid and vancomycin therapy using cohort and case–control studies of incidence and associated risk factors. Eur J Clin Pharmacol 74, 405–411 (2018). https://doi.org/10.1007/s00228-017-2377-1

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  • DOI: https://doi.org/10.1007/s00228-017-2377-1

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