Skip to content
2000
image of Linezolid Related Adverse Effects in Different Populations: A Practical Review

Abstract

Linezolid, an oxazolidinone antibiotic, is used to treat gram-positive infections. Linezolid, an oxazolidinone antibiotic, is used to treat gram-positive infections. However, it may also lead to serious adverse effects, including bone marrow suppression, optic neuropathy it may also lead to serious adverse effects, including bone marrow suppression, optic neuropathy, peripheral neuropathy, hyponatremia, and lactic acidosis. This review evaluates the existing evidence concerning the adverse effects of linezolid in patients undergoing treatment with this medication, both in the short and long term. The objective of this review is to summarize the most significant adverse effects associated with linezolid. A search of PubMed was conducted for articles related to linezolid and its potential adverse effects, which include thrombocytopenia, anemia, neutropenia, lactic acidosis, optic neuropathy, and peripheral neuropathy. Thrombocytopenia frequently develops within the first two weeks of therapy, whereas anemia is more likely to manifest during prolonged treatment courses. Risk factors for linezolid-induced thrombocytopenia include elevated trough concentrations (>8 mg/L), renal impairment, low body weight, and severe liver dysfunction. Patients with multidrug-resistant tuberculosis and bone infections are at an increased risk for anemia, peripheral neuropathy, and optic neuropathy. Additionally, lactic acidosis and hyponatremia can occur at any stage during treatment.

Loading

Article metrics loading...

/content/journals/cds/10.2174/0115748863352325250311080624
2025-03-25
2025-10-15
Loading full text...

Full text loading...

References

  1. Swaney S.M. Aoki H. Ganoza M.C. Shinabarger D.L. The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria. Antimicrob. Agents Chemother. 1998 42 12 3251 3255 10.1128/AAC.42.12.3251 9835522
    [Google Scholar]
  2. Diekema D.J. Jones R.N. Oxazolidinones. Drugs 2000 59 1 7 16 10.2165/00003495‑200059010‑00002 10718097
    [Google Scholar]
  3. Azzouz A Preuss CV Linezolid. StatPearls StatPearls Publishing Treasure Island (FL) 2024
    [Google Scholar]
  4. Dryden M.S. Linezolid pharmacokinetics and pharmacodynamics in clinical treatment. J. Antimicrob. Chemother. 2011 66 Suppl. 4 iv7 iv15 10.1093/jac/dkr072 21521707
    [Google Scholar]
  5. Bandín-Vilar E. García-Quintanilla L. Castro-Balado A. Zarra-Ferro I. González-Barcia M. Campos-Toimil M. Mangas-Sanjuan V. Mondelo-García C. Fernández-Ferreiro A. A review of population pharmacokinetic analyses of linezolid. Clin. Pharmacokinet. 2022 61 6 789 817 10.1007/s40262‑022‑01125‑2 35699914
    [Google Scholar]
  6. Obach R.S. Linezolid metabolism is catalyzed by cytochrome P450 2J2, 4F2, and 1B1. Drug Metab. Dispos. 2022 50 4 413 421 10.1124/dmd.121.000776 35042700
    [Google Scholar]
  7. Oehadian A. Santoso P. Menzies D. Ruslami R. Concise clinical review of hematologic toxicity of linezolid in multidrug-resistant and extensively drug-resistant tuberculosis: Role of mitochondria. Tuberc. Respir. Dis. 2022 85 2 111 121 10.4046/trd.2021.0122 35045688
    [Google Scholar]
  8. Milosevic T.V. Payen V.L. Sonveaux P. Muccioli G.G. Tulkens P.M. Van Bambeke F. Mitochondrial alterations (inhibition of mitochondrial protein expression, oxidative metabolism, and ultrastructure) induced by linezolid and tedizolid at clinically relevant concentrations in cultured human HL-60 promyelocytes and THP-1 monocytes. Antimicrob. Agents Chemother. 2018 62 3 e01599-17 10.1128/AAC.01599‑17 29263063
    [Google Scholar]
  9. Milosevic TV Vertenoeil G Payen VL Sonveaux P Tulkens PM Constantinescu SN Prolonged inhibition and incomplete recovery of mitochondrial function in oxazolidinone-treated megakaryoblastic cell lines. Int. J. Antimicrob. Agents 2019 54 5 661 667 10.1016/j.ijantimicag.2019.07.021
    [Google Scholar]
  10. Tajima M. Kato Y. Matsumoto J. Hirosawa I. Suzuki M. Takashio Y. Yamamoto M. Nishi Y. Yamada H. Linezolid-induced thrombocytopenia is caused by suppression of platelet production via phosphorylation of myosin light chain 2. Biol. Pharm. Bull. 2016 39 11 1846 1851 10.1248/bpb.b16‑00427 27803456
    [Google Scholar]
  11. Tsuji Y. Holford N.H.G. Kasai H. Ogami C. Heo Y.A. Higashi Y. Mizoguchi A. To H. Yamamoto Y. Population pharmacokinetics and pharmacodynamics of linezolid‐induced thrombocytopenia in hospitalized patients. Br. J. Clin. Pharmacol. 2017 83 8 1758 1772 10.1111/bcp.13262 28186644
    [Google Scholar]
  12. Bernstein W.B. Trotta R.F. Rector J.T. Tjaden J.A. Barile A.J. Mechanisms for linezolid-induced anemia and thrombocytopenia. Ann. Pharmacother. 2003 37 4 517 520 10.1345/aph.1C361 12659607
    [Google Scholar]
  13. Choi G.W. Lee J.Y. Chang M.J. Kim Y.K. Cho Y. Yu Y.M. Lee E. Risk factors for linezolid‐induced thrombocytopenia in patients without haemato‐oncologic diseases. Basic Clin. Pharmacol. Toxicol. 2019 124 2 228 234 10.1111/bcpt.13123 30171804
    [Google Scholar]
  14. Sasaki T. Takane H. Ogawa K. Isagawa S. Hirota T. Higuchi S. Horii T. Otsubo K. Ieiri I. Population pharmacokinetic and pharmacodynamic analysis of linezolid and a hematologic side effect, thrombocytopenia, in Japanese patients. Antimicrob. Agents Chemother. 2011 55 5 1867 1873 10.1128/AAC.01185‑10 21357301
    [Google Scholar]
  15. Niwa T. Suzuki A. Sakakibara S. Kasahara S. Yasuda M. Fukao A. Matsuura K. Goto C. Murakami N. Itoh Y. Retrospective cohort chart review study of factors associated with the development of thrombocytopenia in adult Japanese patients who received intravenous linezolid therapy. Clin. Ther. 2009 31 10 2126 2133 10.1016/j.clinthera.2009.10.017 19922883
    [Google Scholar]
  16. Maray I Rodríguez-Ferreras A Álvarez-Asteinza C Alaguero-Calero M Valledor P Fernández J Linezolid induced thrombocytopenia in critically ill patients: Risk factors and development of a machine learning-based prediction model. J. Infect. Chemother. 2022 28 9 1249 1254 10.1016/j.jiac.2022.05.004
    [Google Scholar]
  17. Inoue Y. Takekuma Y. Miyai T. Kashiwagi H. Sato Y. Sugawara M. Imai S. Use of Japanese big data from electronic medical records to investigate risk factors and identify their high-risk combinations for linezolid-induced thrombocytopenia. Eur. J. Clin. Pharmacol. 2023 79 3 415 425 10.1007/s00228‑023‑03455‑x 36715711
    [Google Scholar]
  18. Zhang D. Xu Y. Wang X. Hou L. Xing M. Xu S. Guo R. Luo Y. Risk factors for thrombocytopenia in patients receiving linezolid therapy: A systematic review and meta-analysis. Eur. J. Clin. Pharmacol. 2023 79 10 1303 1314 10.1007/s00228‑023‑03542‑z 37578552
    [Google Scholar]
  19. Dai Y. Jiang S. Chen X. Han L. Zhang C. Yu X. Zhang X. Analysis of the risk factors of linezolid‐related haematological toxicity in Chinese patients. J. Clin. Pharm. Ther. 2021 46 3 807 813 10.1111/jcpt.13359 33555057
    [Google Scholar]
  20. Cojutti P.G. Merelli M. Bassetti M. Pea F. Proactive therapeutic drug monitoring (TDM) may be helpful in managing long-term treatment with linezolid safely: Findings from a monocentric, prospective, open-label, interventional study. J. Antimicrob. Chemother. 2019 74 12 3588 3595 10.1093/jac/dkz374 31504570
    [Google Scholar]
  21. Pea F. Cojutti P.G. Baraldo M. A 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a hospital-wide population of patients receiving conventional dosing: Is there enough evidence for suggesting TDM in the majority of patients? Basic Clin. Pharmacol. Toxicol. 2017 121 4 303 308 10.1111/bcpt.12797 28419737
    [Google Scholar]
  22. Dong H.Y. Xie J. Chen L.H. Wang T.T. Zhao Y.R. Dong Y.L. Therapeutic drug monitoring and receiver operating characteristic curve prediction may reduce the development of linezolid-associated thrombocytopenia in critically ill patients. Eur. J. Clin. Microbiol. Infect. Dis. 2014 33 6 1029 1035 10.1007/s10096‑013‑2041‑3 24515096
    [Google Scholar]
  23. Zhang L. Yan Y. Liao R. Dong H. Effect of platelet parameters on linezolid-related thrombocytopenia in hospitalized patients. Infect. Drug Resist. 2023 16 6145 6154 10.2147/IDR.S408102 37719650
    [Google Scholar]
  24. Fang J. Chen C. Wu Y. Zhang M. Zhang Y. Shi G. Yao Y. Chen H. Bian X. Does the conventional dosage of linezolid necessitate therapeutic drug monitoring?—Experience from a prospective observational study. Ann. Transl. Med. 2020 8 7 493 10.21037/atm.2020.03.207 32395537
    [Google Scholar]
  25. Cazavet J. Bounes F.V. Ruiz S. Seguin T. Crognier L. Rouget A. Fourcade O. Minville V. Conil J.M. Georges B. Risk factor analysis for linezolid-associated thrombocytopenia in critically ill patients. Eur. J. Clin. Microbiol. Infect. Dis. 2020 39 3 527 538 10.1007/s10096‑019‑03754‑1 31853741
    [Google Scholar]
  26. Nukui Y. Hatakeyama S. Okamoto K. Yamamoto T. Hisaka A. Suzuki H. Yata N. Yotsuyanagi H. Moriya K. High plasma linezolid concentration and impaired renal function affect development of linezolid-induced thrombocytopenia. J. Antimicrob. Chemother. 2013 68 9 2128 2133 10.1093/jac/dkt133 23625638
    [Google Scholar]
  27. Matsumoto K. Shigemi A. Takeshita A. Watanabe E. Yokoyama Y. Ikawa K. Morikawa N. Takeda Y. Analysis of thrombocytopenic effects and population pharmacokinetics of linezolid: A dosage strategy according to the trough concentration target and renal function in adult patients. Int. J. Antimicrob. Agents 2014 44 3 242 247 10.1016/j.ijantimicag.2014.05.010 25108880
    [Google Scholar]
  28. Dong H. Xie J. Chen L. Wang T. Sun J. Zhao Y. Dong Y. Developments in the pharmacokinetic/pharmacodynamic index of linezolid: A step toward dose optimization using Monte Carlo simulation in critically ill patients. Int. J. Infect. Dis. 2014 22 35 40 10.1016/j.ijid.2014.01.016 24603161
    [Google Scholar]
  29. Lau C. Marriott D. Bui J. Figtree M. Gould M. Chubaty A. Su Y. Adhikari S. Konecny P. Kozierowski K. Holland T. Milliken E. Akram A. Mcnamara A. Sun Y. Van Hal S. Patanwala A.E. Shahabi-Sirjani A. Gray T. Yeo C.Y. Netluch A. Halena S. Appay M. Alameddine R. Yin F. Nguyen Q. So M.Y. Sandaradura I. Kim H.Y. Galimam S. Cerruto N. Lai T. Gilbey T. Daveson K. Reuter S.E. Penm J. Alffenaar J.W. LInezolid monitoring to minimise toxicity (LIMMIT1): A multicentre retrospective review of patients receiving linezolid therapy and the impact of therapeutic drug monitoring. Int. J. Antimicrob. Agents 2023 61 5 106783 10.1016/j.ijantimicag.2023.106783 36921808
    [Google Scholar]
  30. Abdul-Aziz M.H. Alffenaar J.W.C. Bassetti M. Bracht H. Dimopoulos G. Marriott D. Neely M.N. Paiva J.A. Pea F. Sjovall F. Timsit J.F. Udy A.A. Wicha S.G. Zeitlinger M. De Waele J.J. Roberts J.A. Infection Section of European Society of Intensive Care Medicine (ESICM) Pharmacokinetic/pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Infectious Diseases Group of International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) Infections in the ICU and Sepsis Working Group of International Society of Antimicrobial Chemotherapy (ISAC) Antimicrobial therapeutic drug monitoring in critically ill adult patients: A position paper. Intensive Care Med. 2020 46 6 1127 1153 10.1007/s00134‑020‑06050‑1 32383061
    [Google Scholar]
  31. Zhao W. Kong L. Wu C. Wu X. Prolonged infusion of linezolid is associated with improved pharmacokinetic/pharmacodynamic (PK/PD) profiles in patients with external ventricular drains. Eur. J. Clin. Pharmacol. 2021 77 1 79 86 10.1007/s00228‑020‑02978‑x 32812063
    [Google Scholar]
  32. AL Qamariat Z. Aljaffar A. Alabdulaal Z. Alnezir F. Al-Zawad W. Alqattan M. Almahdi A. Rapid onset and recovery linezolid-induced thrombocytopenia: A large-sample, single-center retrospective cohort study. Drug Healthc. Patient Saf. 2024 16 43 49 10.2147/DHPS.S458284 38800628
    [Google Scholar]
  33. French G. Safety and tolerability of linezolid. J. Antimicrob. Chemother. 2003 51 90002 Suppl. 2 45ii 53 10.1093/jac/dkg253 12730142
    [Google Scholar]
  34. Theil C. Schmidt-Braekling T. Gosheger G. Schwarze J. Dieckmann R. Schneider K.N. Möllenbeck B. Clinical use of linezolid in periprosthetic joint infections – A systematic review. J. Bone Jt. Infect. 2020 6 1 7 16 10.5194/jbji‑6‑7‑2020 32983842
    [Google Scholar]
  35. Imperial M.Z. Nedelman J.R. Conradie F. Savic R.M. Proposed linezolid dosing strategies to minimize adverse events for treatment of extensively drug-resistant tuberculosis. Clin. Infect. Dis. 2022 74 10 1736 1747 10.1093/cid/ciab699 34604901
    [Google Scholar]
  36. Pratama N.Y.I. Zulkarnain B.S. Soedarsono Fatmawati U. Hematological side effect analysis of linezolid in MDR-TB patients with individual therapy. J. Basic Clin. Physiol. Pharmacol. 2021 32 4 777 781 10.1515/jbcpp‑2020‑0468 34214355
    [Google Scholar]
  37. Wasserman S. Brust J.C.M. Abdelwahab M.T. Little F. Denti P. Wiesner L. Gandhi N.R. Meintjes G. Maartens G. Linezolid toxicity in patients with drug-resistant tuberculosis: A prospective cohort study. J. Antimicrob. Chemother. 2022 77 4 1146 1154 10.1093/jac/dkac019 35134182
    [Google Scholar]
  38. Migliori G.B. Eker B. Richardson M.D. Sotgiu G. Zellweger J-P. Skrahina A. Ortmann J. Girardi E. Hoffmann H. Besozzi G. Bevilacqua N. Kirsten D. Centis R. Lange C. TBNET Study Group A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis. Eur. Respir. J. 2009 34 2 387 393 10.1183/09031936.00009509 19282348
    [Google Scholar]
  39. Minson Q. Gentry C.A. Analysis of linezolid-associated hematologic toxicities in a large veterans affairs medical center. Pharmacotherapy 2010 30 9 895 903 10.1592/phco.30.9.895 20795845
    [Google Scholar]
  40. Hanai Y. Matsuo K. Ogawa M. Higashi A. Kimura I. Hirayama S. Kosugi T. Nishizawa K. Yoshio T. A retrospective study of the risk factors for linezolid-induced thrombocytopenia and anemia. J. Infect. Chemother. 2016 22 8 536 542 10.1016/j.jiac.2016.05.003 27321773
    [Google Scholar]
  41. Padmapriyadarsini C. Solanki R. Jeyakumar S.M. Bhatnagar A. Muthuvijaylaksmi M. Jeyadeepa B. Reddy D. Shah P. Sridhar R. Vohra V. Bhui N.K. Linezolid pharmacokinetics and its association with adverse drug reactions in patients with drug-resistant pulmonary tuberculosis. Antibiotics 2023 12 4 714 10.3390/antibiotics12040714 37107075
    [Google Scholar]
  42. Olayanju O. Esmail A. Limberis J. Gina P. Dheda K. Linezolid interruption in patients with fluoroquinolone-resistant tuberculosis receiving a bedaquiline-based treatment regimen. Int. J. Infect. Dis. 2019 85 74 79 10.1016/j.ijid.2019.04.028 31100421
    [Google Scholar]
  43. Zhang X. Falagas M.E. Vardakas K.Z. Wang R. Qin R. Wang J. Liu Y. Systematic review and meta-analysis of the efficacy and safety of therapy with linezolid containing regimens in the treatment of multidrug-resistant and extensively drug-resistant tuberculosis. J. Thorac. Dis. 2015 7 4 603 615 10.3978/j.issn.2072‑1439.2015.03.10 25973226
    [Google Scholar]
  44. Sotgiu G. Centis R. D’Ambrosio L. Alffenaar J.W.C. Anger H.A. Caminero J.A. Castiglia P. De Lorenzo S. Ferrara G. Koh W.J. Schecter G.F. Shim T.S. Singla R. Skrahina A. Spanevello A. Udwadia Z.F. Villar M. Zampogna E. Zellweger J.P. Zumla A. Migliori G.B. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: Systematic review and meta-analysis. Eur. Respir. J. 2012 40 6 1430 1442 10.1183/09031936.00022912 22496332
    [Google Scholar]
  45. Mase A. Lowenthal P. True L. Henry L. Barry P. Flood J. Low-dose linezolid for treatment of patients with multidrug-resistant tuberculosis. Open Forum Infect. Dis. 2022 9 12 ofac500 10.1093/ofid/ofac500 36601556
    [Google Scholar]
  46. Carbajo T. Fenollosa M. Pons R. Calvo C. Lactic acidosis and linezolid-induced pancytopaenia. Nefrologia 2011 31 1 107 108 10.3265/nefrologia.pre2010.jul.10552 21270922
    [Google Scholar]
  47. Gorchynski J. Rose J.K. Complications of MRSA treatment: Linezolid-induced myelosuppression presenting with pancytopenia. West. J. Emerg. Med. 2008 9 3 177 178 19561739
    [Google Scholar]
  48. Halpern M. Linezolid-induced pancytopenia. Clin. Infect. Dis. 2002 35 3 347 348 10.1086/341309 12115109
    [Google Scholar]
  49. Li M.M. Shen W.C. Li Y.J. Teng J. Linezolid-induced pancytopenia in patients using dapagliflozin: A case series. Infect. Drug Resist. 2022 15 5509 5517 10.2147/IDR.S375694 36158232
    [Google Scholar]
  50. Kuter D.J. Tillotson G.S. Hematologic effects of antimicrobials: Focus on the oxazolidinone linezolid. Pharmacotherapy 2001 21 8 1010 1013 10.1592/phco.21.11.1010.34517 11718489
    [Google Scholar]
  51. Liu X. Aoki M. Osa S. Ito C. Saiki R. Nagai T. Enoki Y. Taguchi K. Matsumoto K. Safety of linezolid in patients with decreased renal function and trough monitoring: A systematic review and meta-analysis. BMC Pharmacol. Toxicol. 2022 23 1 89 10.1186/s40360‑022‑00628‑9 36451204
    [Google Scholar]
  52. Jordan K. Linezolid-induced myelosuppression. Ann. Intern. Med. Clin. Cases 2024 3 8 e240263 10.7326/aimcc.2024.0263
    [Google Scholar]
  53. Kobayashi S. Tagawa S. Ogura T. Kitaoka A. Yasu T. Safety of linezolid, rifampicin, and clindamycin combination therapy in patients with prosthetic joint infection. Drug Discov. Ther. 2022 16 3 142 144 10.5582/ddt.2022.01038 35753771
    [Google Scholar]
  54. Faguer S Kamar N Fillola G Guitard J Rostaing L Linezolid-related pancytopenia in organ-transplant patients: Report of two cases. Infection 2007 35 4 275 277 10.1007/s15010‑007‑6197‑6
    [Google Scholar]
  55. Spellberg B. Yoo T. Bayer A.S. Reversal of linezolid-associated cytopenias, but not peripheral neuropathy, by administration of vitamin B6. J. Antimicrob. Chemother. 2004 54 4 832 835 10.1093/jac/dkh405 15317746
    [Google Scholar]
  56. Anger H.A. Dworkin F. Sharma S. Munsiff S.S. Nilsen D.M. Ahuja S.D. Linezolid use for treatment of multidrug-resistant and extensively drug-resistant tuberculosis, New York City, 2000-06. J. Antimicrob. Chemother. 2010 65 4 775 783 10.1093/jac/dkq017 20150181
    [Google Scholar]
  57. Brandariz-Núñez D. Hernández-Corredoira V. Guarc-Prades E. García-Navarro B. Optic neuropathy associated with linezolid: Systematic review of cases. Farm. Hosp. 2019 43 2 61 65 10.7399/fh.11133 30848179
    [Google Scholar]
  58. Joshi L. Taylor S.R.J. Large O. Yacoub S. Lightman S. A case of optic neuropathy after short-term linezolid use in a patient with acute lymphocytic leukemia. Clin. Infect. Dis. 2009 48 7 e73 e74 10.1086/597298 19231981
    [Google Scholar]
  59. Azamfirei L. Copotoiu S.M. Branzaniuc K. Szederjesi J. Copotoiu R. Berteanu C. Complete blindness after optic neuropathy induced by short‐term linezolid treatment in a patient suffering from muscle dystrophy. Pharmacoepidemiol. Drug Saf. 2007 16 4 402 404 10.1002/pds.1320 16998949
    [Google Scholar]
  60. Karuppannasamy D. Raghuram A. Sundar D. Linezolid-induced optic neuropathy. Indian J. Ophthalmol. 2014 62 4 497 500 10.4103/0301‑4738.118451 24088636
    [Google Scholar]
  61. Miller H.V. Cao A.A. McClelland C.M. Lee M.S. Linezolid optic neuropathy. Curr. Opin. Ophthalmol. 2023 34 6 481 486 10.1097/ICU.0000000000000995 37603423
    [Google Scholar]
  62. Yu J.J. Lee D.H. Gallagher S.P. Kenney M.C. Boisvert C.J. Mitochondrial impairment in antibiotic induced toxic optic neuropathies. Curr. Eye Res. 2018 43 10 1199 1204 10.1080/02713683.2018.1504086 30040491
    [Google Scholar]
  63. Toolan K.J. Fondriest J. Keenan K. Mizen T. Stosic M. Linezolid toxic optic neuropathy: A case report and review of visual prognosis. Am. J. Ophthalmol. Case Rep. 2023 32 101922 10.1016/j.ajoc.2023.101922 37680308
    [Google Scholar]
  64. Zhang P. Li W. Liu M. Zhan S. Zhang H. Deng G. Chen X. Linezolid-associated neuropathy in patients with MDR/XDR tuberculosis in Shenzhen, China. Infect. Drug Resist. 2022 15 2617 2624 10.2147/IDR.S365371 35634579
    [Google Scholar]
  65. Conradie F. Bagdasaryan T.R. Borisov S. Howell P. Mikiashvili L. Ngubane N. Samoilova A. Skornykova S. Tudor E. Variava E. Yablonskiy P. Everitt D. Wills G.H. Sun E. Olugbosi M. Egizi E. Li M. Holsta A. Timm J. Bateson A. Crook A.M. Fabiane S.M. Hunt R. McHugh T.D. Tweed C.D. Foraida S. Mendel C.M. Spigelman M. ZeNix Trial Team Bedaquiline–pretomanid–linezolid regimens for drug-resistant tuberculosis. N. Engl. J. Med. 2022 387 9 810 823 10.1056/NEJMoa2119430 36053506
    [Google Scholar]
  66. Conradie F. Diacon A.H. Ngubane N. Howell P. Everitt D. Crook A.M. Mendel C.M. Egizi E. Moreira J. Timm J. McHugh T.D. Wills G.H. Bateson A. Hunt R. Van Niekerk C. Li M. Olugbosi M. Spigelman M. Nix-TB Trial Team Treatment of highly drug-resistant pulmonary tuberculosis. N. Engl. J. Med. 2020 382 10 893 902 10.1056/NEJMoa1901814 32130813
    [Google Scholar]
  67. Lee S. Kang B.H. Ryu W.Y. Um S.J. Roh M.S. Son C. Is severe and long-lasting linezolid-induced optic neuropathy reversible? Intern. Med. 2018 57 24 3611 3613 10.2169/internalmedicine.1344‑18 30101940
    [Google Scholar]
  68. Jaspard M. Butel N. El Helali N. Marigot-Outtandy D. Guillot H. Peytavin G. Veziris N. Bodaghi B. Flandre P. Petitjean G. Caumes E. Pourcher V. Linezolid-associated neurologic adverse events in patients with multidrug-resistant tuberculosis, France. Emerg. Infect. Dis. 2020 26 8 1792 1800 10.3201/eid2608.191499 32687026
    [Google Scholar]
  69. Libershteyn Y. Ethambutol/linezolid toxic optic neuropathy. Optom. Vis. Sci. 2016 93 2 211 217 10.1097/OPX.0000000000000783 26636399
    [Google Scholar]
  70. Chung C. Jo K-W. Shim T.S. Treatment outcome, recurrence and safety of multidrug-resistant TB treated with low-dose linezolid. Int. J. Tuberc. Lung Dis. 2023 27 12 918 924 10.5588/ijtld.23.0068 38042970
    [Google Scholar]
  71. Tang S. Yao L. Hao X. Zhang X. Liu G. Liu X. Wu M. Zen L. Sun H. Liu Y. Gu J. Lin F. Wang X. Zhang Z. Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: A study in China. Eur. Respir. J. 2015 45 1 161 170 10.1183/09031936.00035114 25234807
    [Google Scholar]
  72. Bolhuis M.S. Tiberi S. Sotgiu G. De Lorenzo S. Kosterink J.G.W. van der Werf T.S. Migliori G.B. Alffenaar J.W.C. Linezolid tolerability in multidrug-resistant tuberculosis: A retrospective study. Eur. Respir. J. 2015 46 4 1205 1207 10.1183/13993003.00606‑2015 26160870
    [Google Scholar]
  73. Yuan Y. Li J. Chen Y. Cai Q. Xu Y. Lin L. Lang Y. Guo S. Zhang R. Cai X. Mechanism underlying linezolid-induced peripheral neuropathy in multidrug-resistant tuberculosis. Front. Pharmacol. 2022 13 946058 10.3389/fphar.2022.946058 36160387
    [Google Scholar]
  74. Rho J.P. Sia I.G. Crum B.A. Dekutoski M.B. Trousdale R.T. Linezolid-associated peripheral neuropathy. Mayo Clin. Proc. 2004 79 7 927 930 10.4065/79.7.927 15244392
    [Google Scholar]
  75. Bobylev I. Maru H. Joshi A.R. Lehmann H.C. Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy. J. Antimicrob. Chemother. 2016 71 3 685 691 10.1093/jac/dkv386 26612872
    [Google Scholar]
  76. Santini A. Ronchi D. Garbellini M. Piga D. Protti A. Linezolid-induced lactic acidosis: The thin line between bacterial and mitochondrial ribosomes. Expert Opin. Drug Saf. 2017 16 7 833 843 10.1080/14740338.2017.1335305 28538105
    [Google Scholar]
  77. Mao Y. Dai D. Jin H. Wang Y. The risk factors of linezolid-induced lactic acidosis. Medicine 2018 97 36 e12114 10.1097/MD.0000000000012114 30200095
    [Google Scholar]
  78. Liu T. Hu C. Wu J. Liu M. Que Y. Wang J. Fang X. Xu G. Li H. Incidence and associated risk factors for lactic acidosis induced by linezolid therapy in a case–control study in patients older than 85 years. Front. Med. 2021 8 604680 10.3389/fmed.2021.604680 33732712
    [Google Scholar]
  79. Ghandour M. Alkassis S. Bhat Z.Y. Linezolid-induced lactic acidosis. Am. J. Ther. 2023 30 2 175 178 10.1097/MJT.0000000000001337 33538490
    [Google Scholar]
  80. Mori N. Kamimura Y. Kimura Y. Hirose S. Aoki Y. Bito S. 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. 2018 74 4 405 411 10.1007/s00228‑017‑2377‑1 29222713
    [Google Scholar]
  81. Bai A.D. McKenna S. Wise H. Loeb M. Gill S.S. Safety profile of linezolid in older adults with renal impairment: A population-based retrospective cohort study. Open Forum Infect. Dis. 2022 9 12 ofac669 10.1093/ofid/ofac669 36601560
    [Google Scholar]
  82. Im J.H. Baek J.H. Kwon H.Y. Lee J.S. Incidence and risk factors of linezolid-induced lactic acidosis. Int. J. Infect. Dis. 2015 31 47 52 10.1016/j.ijid.2014.12.009 25499040
    [Google Scholar]
  83. Kronen T Agrawal A Reddy P. Acute onset lactic acidosis secondary to linezolid. Cureus 2023 15 3 e35891 10.7759/cureus.35891
    [Google Scholar]
  84. Cheng C.N. Lin S.W. Wu C.C. Early linezolid-associated lactic acidosis in a patient with Child’s class C liver cirrhosis and end stage renal disease. J. Infect. Chemother. 2018 24 10 841 844 10.1016/j.jiac.2018.02.002 29503228
    [Google Scholar]
  85. Zhang N. Zhang F. Chen Z. Huang R. Xia J. Liu J. Successful treatment of linezolid-induced severe lactic acidosis with continuous venovenous hemodiafiltration: A case report. Saudi Pharm. J. 2022 30 2 108 111 10.1016/j.jsps.2021.12.021 35528852
    [Google Scholar]
  86. Sawyer A.J. Haley H.L. Baty S.R. McGuffey G.E. Eiland E.H. III Linezolid-induced lactic acidosis corrected with sustained low-efficiency dialysis: A case report. Am. J. Kidney Dis. 2014 64 3 457 459 10.1053/j.ajkd.2014.04.032 24961626
    [Google Scholar]
  87. De Bus L. Depuydt P. Libbrecht L. Vandekerckhove L. Nollet J. Benoit D. Vogelaers D. Van Vlierberghe H. Severe drug-induced liver injury associated with prolonged use of linezolid. J. Med. Toxicol. 2010 6 3 322 326 10.1007/s13181‑010‑0047‑0 20358416
    [Google Scholar]
  88. Tanaka R. Morinaga Y. Iwao M. Tatsuta R. Hashimoto T. Hiramatsu K. Itoh H. Comparison of incidence of hyponatremia between linezolid and vancomycin by propensity score matching analysis. Biol. Pharm. Bull. 2023 46 10 1365 1370 10.1248/bpb.b23‑00038 37779038
    [Google Scholar]
  89. Dong Q.W. Tang L. Ge D.D. Zhou T.Y. Zhao Y.C. Ma C.H. Sun P. A case of linezolid-induced SIADH in elderly and a review of the literature. Eur. Rev. Med. Pharmacol. Sci. 2022 26 16 5706 5709 10.26355/eurrev_202208_29505 36066143
    [Google Scholar]
  90. Nishi Y. Ogami C. Tsuji Y. Kawasuji H. Yamada H. Kawai S. Sakamaki I. To H. Yamamoto Y. Evaluation of the relationship between linezolid exposure and hyponatremia. J. Infect. Chemother. 2021 27 2 165 171 10.1016/j.jiac.2020.08.017 32933858
    [Google Scholar]
  91. Tanaka R. Suzuki Y. Morinaga Y. Iwao M. Takumi Y. Hashinaga K. Tatsuta R. Hiramatsu K. Kadota J. Itoh H. A retrospective test for a possible relationship between linezolid-induced thrombocytopenia and hyponatraemia. J. Clin. Pharm. Ther. 2021 46 2 343 351 10.1111/jcpt.13287 33016566
    [Google Scholar]
  92. Tanaka R. Suzuki Y. Takumi Y. Iwao M. Sato Y. Hashinaga K. Hiramatsu K. Kadota J. Itoh H. A retrospective analysis of risk factors for linezolid-associated hyponatremia in japanese patients. Biol. Pharm. Bull. 2016 39 12 1968 1973 10.1248/bpb.b16‑00418 27904038
    [Google Scholar]
  93. Shibata Y. Hagihara M. Asai N. Shiota A. Hirai J. Mori N. Mikamo H. A retrospective study to compare the incidence of hyponatremia after administration between linezolid and tedizolid. Antibiotics 2023 12 2 345 10.3390/antibiotics12020345 36830256
    [Google Scholar]
  94. Singhania S.V.K. Shenoy S. Kapoor D. Linezolid-induced rare triad of hypoglycaemia, bone marrow suppression and hyponatraemia in elderly. J. Clin. Pharm. Ther. 2020 45 2 376 378 10.1111/jcpt.13069 31657870
    [Google Scholar]
  95. Ioannou P. Stavroulaki M. Mavrikaki V. Papakitsou I. Panagiotakis S. A case of severe hyponatremia due to linezolid-induced SIADH. J. Clin. Pharm. Ther. 2018 43 3 434 436 10.1111/jcpt.12681 29542179
    [Google Scholar]
  96. Baik S.H. Choi Y.K. Kim H.S. Yoon Y.K. Sohn J.W. Kim M.J. A probable case of syndrome of inappropriate antidiuretic hormone secretion associated with linezolid. Am. J. Health Syst. Pharm. 2015 72 21 1865 1869 10.2146/ajhp150208 26490820
    [Google Scholar]
  97. Swart R.M. Hoorn E.J. Betjes M.G. Zietse R. Hyponatremia and inflammation: The emerging role of interleukin-6 in osmoregulation. Nephron, Physiol. 2011 118 2 p45 p51 10.1159/000322238 21196778
    [Google Scholar]
  98. Ide T. Takesue Y. Ikawa K. Morikawa N. Ueda T. Takahashi Y. Nakajima K. Takeda K. Nishi S. Population pharmacokinetics/pharmacodynamics of linezolid in sepsis patients with and without continuous renal replacement therapy. Int. J. Antimicrob. Agents 2018 51 5 745 751 10.1016/j.ijantimicag.2018.01.021 29425834
    [Google Scholar]
  99. Brier M.E. Stalker D.J. Aronoff G.R. Batts D.H. Ryan K.K. O’Grady M. Hopkins N.K. Jungbluth G.L. Pharmacokinetics of linezolid in subjects with renal dysfunction. Antimicrob. Agents Chemother. 2003 47 9 2775 2780 10.1128/AAC.47.9.2775‑2780.2003 12936973
    [Google Scholar]
  100. Zheng J. Sun Z. Sun L. Zhang X. Hou G. Han Q. Li X. Liu G. Gao Y. Ye M. Wang H. Yu K. Pharmacokinetics and pharmacodynamics of linezolid in patients with sepsis receiving continuous venovenous hemofiltration and extended daily hemofiltration. J. Infect. Dis. 2020 221 Suppl. 2 S279 S287 10.1093/infdis/jiz566 32176792
    [Google Scholar]
  101. Swoboda S. Ober M.C. Lichtenstern C. Saleh S. Schwenger V. Sonntag H.G. Haefeli W.E. Hempel G. Hoppe-Tichy T. Weigand M.A. Pharmacokinetics of linezolid in septic patients with and without extended dialysis. Eur. J. Clin. Pharmacol. 2010 66 3 291 298 10.1007/s00228‑009‑0766‑9 20013257
    [Google Scholar]
  102. El-Assal M.I. Helmy S.A. Single-dose linezolid pharmacokinetics in critically ill patients with impaired renal function especially chronic hemodialysis patients. Biopharm. Drug Dispos. 2014 35 7 405 416 10.1002/bdd.1910 25044219
    [Google Scholar]
  103. Wang X. Wang Y. Yao F. Chen S. Hou Y. Zheng Z. Luo J. Qiu B. Li Z. Wang Y. Wu Z. Lan J. Chen C. Pharmacokinetics of linezolid dose adjustment for creatinine clearance in critically Ill patients: A multicenter, prospective, open-label, observational study. Drug Des. Devel. Ther. 2021 15 2129 2141 10.2147/DDDT.S303497 34040351
    [Google Scholar]
  104. Crass R.L. Cojutti P.G. Pai M.P. Pea F. Reappraisal of linezolid dosing in renal impairment to improve safety. Antimicrob. Agents Chemother. 2019 63 8 e00605-19 10.1128/AAC.00605‑19 31109977
    [Google Scholar]
  105. Kawasuji H. Tsuji Y. Ogami C. Kimoto K. Ueno A. Miyajima Y. Kawago K. Sakamaki I. Yamamoto Y. Proposal of initial and maintenance dosing regimens with linezolid for renal impairment patients. BMC Pharmacol. Toxicol. 2021 22 1 13 10.1186/s40360‑021‑00479‑w 33663616
    [Google Scholar]
  106. Kato H. Hamada Y. Hagihara M. Hirai J. Yamagishi Y. Matsuura K. Mikamo H. Bicytopenia, especially thrombocytopenia in hemodialysis and non-hemodialysis patients treated with linezolid therapy. J. Infect. Chemother. 2015 21 10 707 712 10.1016/j.jiac.2015.06.007 26231318
    [Google Scholar]
  107. Laarhuis S.R.E. Kerskes C.H.M. Nijziel M.R. van Wensen R.J.A. Touw D.J. Linezolid-induced thrombocytopenia in patients with renal impairment: A case series, review and dose advice. Drugs R D. 2024 24 1 109 115 10.1007/s40268‑024‑00458‑6 38480595
    [Google Scholar]
  108. Luque S. Muñoz-Bermudez R. Echeverría-Esnal D. Sorli L. Campillo N. Martínez-Casanova J. González-Colominas E. Álvarez-Lerma F. Horcajada J.P. Grau S. Roberts J.A. Linezolid dosing in patients with liver cirrhosis: Standard dosing risk toxicity. Ther. Drug Monit. 2019 41 6 732 739 10.1097/FTD.0000000000000665 31259884
    [Google Scholar]
  109. Liao R. Dong Y. Chen L. Wang T. Li H. Dong H. A standard dose of linezolid puts patients with hepatic impairment at risk of overexposure. Eur. J. Clin. Pharmacol. 2023 79 1 149 157 10.1007/s00228‑022‑03427‑7 36434292
    [Google Scholar]
  110. Zhang S. Zhu Z. Chen Z. Li Y. Zou Y. Yan M. Xu Y. Wang F. Liu M. Zhang M. Zhang B. Population pharmacokinetics and dosage optimization of linezolid in patients with liver dysfunction. Antimicrob. Agents Chemother. 2020 64 6 e00133-20 10.1128/AAC.00133‑20 32253210
    [Google Scholar]
  111. Tikiso T. Fuhrmann V. König C. Jarczak D. Iwersen-Bergmann S. Kluge S. Wicha S.G. Grensemann J. Acute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: An observational study. Ann. Intensive Care 2023 13 1 83 10.1186/s13613‑023‑01184‑z 37698659
    [Google Scholar]
  112. Zhang Y.M. Yu W. Zhou N. Li J.Z. Xu L.C. Xie Z.Y. Lu Y.F. Li L.J. High frequency of thrombocytopenia in patients with acute-on-chronic liver failure treated with linezolid. Hepatobiliary Pancreat. Dis. Int. 2015 14 3 287 292 10.1016/S1499‑3872(15)60379‑4 26063030
    [Google Scholar]
  113. Alraish R. Wicha S.G. Frey O.R. Roehr A.C. Pratschke J. Stockmann M. Wuensch T. Kaffarnik M. Liver function, quantified by the LiMAx test, as a predictor for the clinical outcome of critically ill patients treated with linezolid. Technol. Health Care 2022 30 2 309 321 10.3233/THC‑191847 34180433
    [Google Scholar]
  114. Wicha S.G. Frey O.R. Roehr A.C. Pratschke J. Stockmann M. Alraish R. Wuensch T. Kaffarnik M. Linezolid in liver failure: Exploring the value of the maximal liver function capacity (LiMAx) test in a pharmacokinetic pilot study. Int. J. Antimicrob. Agents 2017 50 4 557 563 10.1016/j.ijantimicag.2017.06.023 28711678
    [Google Scholar]
  115. Cremaschi E. Maggiore U. Maccari C. Cademartiri C. Andreoli R. Fiaccadori E. Linezolid levels in a patient with biliary tract sepsis, severe hepatic failure and acute kidney injury on sustained low-efficiency dialysis (SLED). Minerva Anestesiol. 2010 76 11 961 964 21102392
    [Google Scholar]
  116. Asadi M.R. Torkaman G. Hedayati M. Mohajeri-Tehrani M.R. Ahmadi M. Gohardani R.F. Angiogenic effects of low-intensity cathodal direct current on ischemic diabetic foot ulcers: A randomized controlled trial. Diabetes Res. Clin. Pract. 2017 127 147 155 10.1016/j.diabres.2017.03.012 28371685
    [Google Scholar]
  117. WHO consolidated guidelines on tuberculosis. Module 4: Treatment - Drug-resistant tuberculosis treatment Geneva World Health Organization 2022
    [Google Scholar]
  118. Borisov S.E. Dheda K. Enwerem M. Romero Leyet R. D’Ambrosio L. Centis R. Sotgiu G. Tiberi S. Alffenaar J.W. Maryandyshev A. Belilovski E. Ganatra S. Skrahina A. Akkerman O. Aleksa A. Amale R. Artsukevich J. Bruchfeld J. Caminero J.A. Carpena Martinez I. Codecasa L. Dalcolmo M. Denholm J. Douglas P. Duarte R. Esmail A. Fadul M. Filippov A. Davies Forsman L. Gaga M. Garcia-Fuertes J.A. García-García J.M. Gualano G. Jonsson J. Kunst H. Lau J.S. Lazaro Mastrapa B. Teran Troya J.L. Manga S. Manika K. González Montaner P. Mullerpattan J. Oelofse S. Ortelli M. Palmero D.J. Palmieri F. Papalia A. Papavasileiou A. Payen M.C. Pontali E. Robalo Cordeiro C. Saderi L. Sadutshang T.D. Sanukevich T. Solodovnikova V. Spanevello A. Topgyal S. Toscanini F. Tramontana A.R. Farokh Udwadia Z. Viggiani P. White V. Zumla A. Migliori G.B. Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: A multicentre study. Eur. Respir. J. 2017 49 5 1700387 10.1183/13993003.00387‑2017 28529205
    [Google Scholar]
  119. Zhang H. He Y. Davies Forsman L. Paues J. Werngren J. Niward K. Schön T. Bruchfeld J. Alffenaar J.W. Hu Y. Population pharmacokinetics and dose evaluations of linezolid in the treatment of multidrug-resistant tuberculosis. Front. Pharmacol. 2023 13 1032674 10.3389/fphar.2022.1032674 36699070
    [Google Scholar]
  120. Cheng J. Yuan Y. Li J. Zhang R. Fan X. Xu Z. Lin H. Cai X. Zheng M. Therapeutic drug monitoring of linezolid in drug-resistant tuberculosis patients: Clinical factors and hematological toxicities. Infect. Drug Resist. 2024 17 2531 2540 10.2147/IDR.S464429 38933777
    [Google Scholar]
  121. Zou F. Cui Z. Lou S. Ou Y. Zhu C. Shu C. Chen J. Zhao R. Wu Z. Wang L. Chen Z. Chen H. Lan Y. Adverse drug events associated with linezolid administration: A real-world pharmacovigilance study from 2004 to 2023 using the FAERS database. Front. Pharmacol. 2024 15 1338902 10.3389/fphar.2024.1338902 38434706
    [Google Scholar]
  122. Veerman K. Goosen J. Spijkers K. Jager N. Heesterbeek P. Telgt D. Prolonged use of linezolid in bone and joint infections: A retrospective analysis of adverse effects. J. Antimicrob. Chemother. 2023 78 11 2660 2666 10.1093/jac/dkad276 37681570
    [Google Scholar]
  123. Senneville E. Legout L. Valette M. Yazdanpanah Y. Giraud F. Beltrand E. Obert G. Dubreuil L. Migaud H. Mouton Y. Risk factors for anaemia in patients on prolonged linezolid therapy for chronic osteomyelitis: A case–control study. J. Antimicrob. Chemother. 2004 54 4 798 802 10.1093/jac/dkh409 15329363
    [Google Scholar]
  124. Morata L. Senneville E. Bernard L. Nguyen S. Buzelé R. Druon J. Tornero E. Mensa J. Soriano A. A retrospective review of the clinical experience of linezolid with or without rifampicin in prosthetic joint infections treated with debridement and implant retention. Infect. Dis. Ther. 2014 3 2 235 243 10.1007/s40121‑014‑0032‑z 25139552
    [Google Scholar]
  125. Muzevich K.M. Lee K.B. Subtherapeutic linezolid concentrations in a patient with morbid obesity and methicillin-resistant Staphylococcus aureus pneumonia: Case report and review of the literature. Ann. Pharmacother. 2013 47 6 e25 10.1345/aph.1R707 23673532
    [Google Scholar]
  126. Simon P. Busse D. Petroff D. Dorn C. Ehmann L. Hochstädt S. Girrbach F. Dietrich A. Zeitlinger M. Kees F. Kloft C. Wrigge H. Linezolid concentrations in plasma and subcutaneous tissue are reduced in obese patients, resulting in a higher risk of underdosing in critically ill patients: A controlled clinical pharmacokinetic study. J. Clin. Med. 2020 9 4 1067 10.3390/jcm9041067 32283731
    [Google Scholar]
  127. Cojutti P. Pai M.P. Pea F. Population pharmacokinetics and dosing considerations for the use of linezolid in overweight and obese adult patients. Clin. Pharmacokinet. 2018 57 8 989 1000 10.1007/s40262‑017‑0606‑5 29080937
    [Google Scholar]
  128. Blackman A.L. Jarugula P. Nicolau D.P. Chui S.H. Joshi M. Heil E.L. Gopalakrishnan M. Evaluation of linezolid pharmacokinetics in critically ill obese patients with severe skin and soft tissue infections. Antimicrob. Agents Chemother. 2021 65 2 e01619-20 10.1128/AAC.01619‑20 33257446
    [Google Scholar]
  129. Xie F. Mantzarlis K. Malliotakis P. Koulouras V. Degroote S. Koulenti D. Blot S. Boussery K. Van Bocxlaer J. Colin P. Zakynthinos E. Georgopoulos D. Papathanasiou A. Arvaniti K. Matamis D. Spring A. Bekos V. Komnos A. Zafeiridis T. Vogelaers D. LIMOP study collaborators Pharmacokinetic evaluation of linezolid administered intravenously in obese patients with pneumonia. J. Antimicrob. Chemother. 2019 74 3 667 674 10.1093/jac/dky500 30535122
    [Google Scholar]
  130. Ehmann L. Simon P. Busse D. Petroff D. Dorn C. Huisinga W. Dietrich A. Zeitlinger M. Wrigge H. Kloft C. Risk of target non-attainment in obese compared to non-obese patients in calculated linezolid therapy. Clin. Microbiol. Infect. 2020 26 9 1222 1228 10.1016/j.cmi.2020.04.009 32311473
    [Google Scholar]
/content/journals/cds/10.2174/0115748863352325250311080624
Loading
/content/journals/cds/10.2174/0115748863352325250311080624
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: hyponatremia ; lactic acidosis ; anemia ; neuropathy ; thrombocytopenia ; oxazolidinone ; Linezolid
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test