Antibiotic-Induced Neurotoxicity

  • Shamik BhattacharyyaEmail author
  • Ryan Darby
  • Aaron L. Berkowitz
Central Nervous System Infections (J Lyons, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Central Nervous System Infections


Antibiotic neurotoxicity is rare but can cause significant morbidity when it occurs. The risk of antibiotic neurotoxicity appears to be highest in patients who are older, have impaired renal function, or have preexisting neurologic conditions. This review describes the clinical features of the most common antibiotic toxicities affecting the nervous system: seizures, encephalopathy, optic neuropathy, peripheral neuropathy, and exacerbation of myasthenia gravis.


Neurotoxicity Antibiotics Seizures Encephalopathy Neuropathy Myasthenia gravis 


Compliance with Ethics Guidelines

Conflict of Interest

Ryan Darby and Shamik Bhattacharyya have no conflict of interest relevant to the manuscript. Dr. Berkowitzhas no conflicts of interests relevant to the manuscript, but receives royalties from Clinical Pathophysiology Made Ridiculously Simple (Medmaster) and The Improvising Mind (Oxford).

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.


  1. 1.
    Frytak S, Moertel CH, Childs DS. Neurologic toxicity associated with high-dose metronidazole therapy. Ann Intern Med. 1978;88:361–2.PubMedCrossRefGoogle Scholar
  2. 2.
    Maw G, Aitken P. Isoniazid overdose: a case series, literature review and survey of antidote availability. Clin Drug Investig. 2003;23:479–85.PubMedCrossRefGoogle Scholar
  3. 3.
    Grøndahl TO, Langmoen IA. Epileptogenic effect of antibiotic drugs. J Neurosurg. 1993;78:938–43.PubMedCrossRefGoogle Scholar
  4. 4.
    Lode H. Potential interactions of the extended-spectrum fluoroquinolones with the CNS. Drug Saf Int J Med Toxicol Drug Exp. 1999;21:123–35.CrossRefGoogle Scholar
  5. 5.
    Linden P. Safety profile of meropenem: an updated review of over 6,000 patients treated with meropenem. Drug Saf Int J Med Toxicol Drug Exp. 2007;30:657–68.CrossRefGoogle Scholar
  6. 6.
    Arcieri GM, Becker N, Esposito B, Griffith E, Heyd A, Neumann C, et al. Safety of intravenous ciprofloxacin. A review. Am J Med. 1989;87:92S–7S.PubMedCrossRefGoogle Scholar
  7. 7.
    Yagawa K. Latest industry information on the safety profile of levofloxacin in Japan. Chemotherapy. 2001;47 Suppl 3:38–43. discussion 44–48.PubMedCrossRefGoogle Scholar
  8. 8.
    Moellering Jr RC, Eliopoulos GM, Sentochnik DE. The carbapenems: new broad spectrum beta-lactam antibiotics. J Antimicrob Chemother. 1989;24(Suppl A):1–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Cannon JP, Lee TA, Clark NM, Setlak P, Grim SA. The risk of seizures among the carbapenems: a meta-analysis. J Antimicrob Chemother 2014Google Scholar
  10. 10.
    Schliamser SE, Cars O, Norrby SR. Neurotoxicity of beta-lactam antibiotics: predisposing factors and pathogenesis. J Antimicrob Chemother. 1991;27:405–25.PubMedCrossRefGoogle Scholar
  11. 11.
    Lerner PI, Smith H, Weinstein L. Penicillin neurotoxicity. Ann N Y Acad Sci. 1967;145:310–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Chang Y-M. Cefepime-induced nonconvulsive status epilepticus as a cause of confusion in an elderly patient: a case report. J Formos Med Assoc Taiwan Yi Zhi 2013Google Scholar
  13. 13.
    Towne AR, Waterhouse EJ, Boggs JG, Garnett LK, Brown AJ, Smith JR, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology. 2000;54:340–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Holtkamp M, Meierkord H. Nonconvulsive status epilepticus: a diagnostic and therapeutic challenge in the intensive care setting. Ther Adv Neurol Disord. 2011;4:169–81.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Mancl EE, Gidal BE. The effect of carbapenem antibiotics on plasma concentrations of valproic acid. Ann Pharmacother. 2009;43:2082–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Spriet I, Goyens J, Meersseman W, Wilmer A, Willems L, Van Paesschen W. Interaction between valproate and meropenem: a retrospective study. Ann Pharmacother. 2007;41:1130–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Gu J, Huang Y. Effect of concomitant administration of meropenem and valproic acid in an elderly Chinese patient. Am J Geriatr Pharmacother. 2009;7:26–33.PubMedCrossRefGoogle Scholar
  18. 18.
    Rose JQ, Choi HK, Schentag JJ, Kinkel WR, Jusko WJ. Intoxication caused by interaction of chloramphenicol and phenytoin. J Am Med Assoc. 1977;237:2630–1.CrossRefGoogle Scholar
  19. 19.
    O’Connor NK, Fris J. Clarithromycin-carbamazepine interaction in a clinical setting. J Am Board Fam Pract. 1994;7:489–92.PubMedGoogle Scholar
  20. 20.
    Tagawa T, Mimaki T, Ono J, Tanaka J, Suzuki Y, Itagaki T, et al. Erythromycin-induced carbamazepine intoxication in two epileptic children. Jpn J Psychiatr Neurol. 1989;43:513–4.Google Scholar
  21. 21.
    Block SH. Carbamazepine-isoniazid interaction. Pediatrics. 1982;69:494–5.PubMedGoogle Scholar
  22. 22.
    Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis and treatment. Crit Care Clin. 2008;24:657–722. vii.PubMedCrossRefGoogle Scholar
  23. 23.
    Bischoff A, Meier C, Roth F. Gentamicin neurotoxicity (polyneuropathy–encephalopathy). Schweiz Med Wochenschr. 1977;107:3–8.PubMedGoogle Scholar
  24. 24.
    Fletcher J, Aykroyd LE, Feucht EC, Curtis JM. Early onset probable linezolid-induced encephalopathy. J Neurol. 2010;257:433–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Saidinejad M, Ewald MB, Shannon MW. Transient psychosis in an immune-competent patient after oral trimethoprim-sulfamethoxazole administration. Pediatrics. 2005;115:e739–741.PubMedCrossRefGoogle Scholar
  26. 26.
    Cooper GS, Blades EW, Remler BF, Salata RA, Bennert KW, Jacobs GH. Central nervous system Whipple’s disease: relapse during therapy with trimethoprim-sulfamethoxazole and remission with cefixime. Gastroenterology. 1994;106:782–6.PubMedGoogle Scholar
  27. 27.
    Grill MF, Maganti RK. Neurotoxic effects associated with antibiotic use: management considerations. Br J Clin Pharmacol. 2011;72:381–93.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Kuriyama A, Jackson JL, Doi A, Kamiya T. Metronidazole-induced central nervous system toxicity: a systematic review. Clin Neuropharmacol. 2011;34:241–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Bandettini di Poggio M, Anfosso S, Audenino D, Primavera A. Clarithromycin-induced neurotoxicity in adults. J Clin Neurosci Off J Neurosurg Soc Australas. 2011;18:313–8.Google Scholar
  30. 30.
    Sharma P, Sharma R. Toxic optic neuropathy. Indian J Ophthalmol. 2011;59:137–41.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Melamud A, Kosmorsky GS, Lee MS. Ocular ethambutol toxicity. Mayo Clin Proc. 2003;78:1409–11.PubMedCrossRefGoogle Scholar
  32. 32.
    Samarakoon N, Harrisberg B, Ell J. Ciprofloxacin-induced toxic optic neuropathy. Clin Exp Ophthalmol. 2007;35:102–4.CrossRefGoogle Scholar
  33. 33.
    Das S, Mondal S. Oral levofloxacin-induced optic neuritis progressing in loss of vision. Ther Drug Monit. 2012;34:124–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Godel V, Nemet P, Lazar M. Chloramphenicol optic neuropathy. Arch Ophthalmol. 1980;98:1417–21.PubMedCrossRefGoogle Scholar
  35. 35.
    McGrath NM, Kent-Smith B, Sharp DM. Reversible optic neuropathy due to metronidazole. Clin Exp Ophthalmol. 2007;35:585–6.CrossRefGoogle Scholar
  36. 36.
    Van Stavern GP. Metabolic, hereditary, traumatic, and neoplastic optic neuropathies. Continuum (Minneap Minn). 2014;20:877–906.Google Scholar
  37. 37.
    Lessell S. Histopathology of experimental ethambutol intoxication. Invest Ophthalmol Vis Sci. 1976;15:765–9.PubMedGoogle Scholar
  38. 38.
    Choi SY, Hwang JM. Optic neuropathy associated with ethambutol in Koreans. Korean J Ophthalmol. 1997;11:106–10.PubMedCrossRefGoogle Scholar
  39. 39.
    Javaheri M, Khurana RN, O’hearn TM, Lai MM, Sadun AA. Linezolid-induced optic neuropathy: a mitochondrial disorder? Br J Ophthalmol. 2007;91:111–5.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Rucker JC, Hamilton SR, Bardenstein D, Isada CM, Lee MS. Linezolid-associated toxic optic neuropathy. Neurology. 2006;66:595–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Weimer LH, Sachdev N. Update on medication-induced peripheral neuropathy. Curr Neurol Neurosci Rep. 2009;9:69–75.PubMedCrossRefGoogle Scholar
  42. 42.
    Manji H. Drug-induced neuropathies. Handb Clin Neurol. 2013;115:729–42.PubMedCrossRefGoogle Scholar
  43. 43.
    Pratt RW, Weimer LH. Medication and toxin-induced peripheral neuropathy. Semin Neurol. 2005;25:204–16.PubMedCrossRefGoogle Scholar
  44. 44.
    Hobson-Webb LD, Roach ES, Donofrio PD. Metronidazole: newly recognized cause of autonomic neuropathy. J Child Neurol. 2006;21:429–31.PubMedGoogle Scholar
  45. 45.
    Saqueton AC, Lorincz AL, Vick NA, Hamer RD. Dapsone and peripheral motor neuropathy. Arch Dermatol. 1969;100:214–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Narita M, Tsuji BT, Yu VL. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy. 2007;27:1189–97.PubMedCrossRefGoogle Scholar
  47. 47.
    Carroll MW, Jeon D, Mountz JM, Lee JD, Jeong YJ, Zia N, et al. Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis. Antimicrob Agents Chemother. 2013;57:3903–9.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Sotgiu G, Centis R, D’Ambrosio L, Alffenaar J-WC, Anger HA, Caminero JA, et al. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J. 2012;40:1430–42.PubMedCrossRefGoogle Scholar
  49. 49.
    Boyce EG, Cookson ET, Bond WS. Persistent metronidazole-induced peripheral neuropathy. DICP Ann Pharmacother. 1990;24:19–21.Google Scholar
  50. 50.
    Bressler AM, Zimmer SM, Gilmore JL, Somani J. Peripheral neuropathy associated with prolonged use of linezolid. Lancet Infect Dis. 2004;4:528–31.PubMedCrossRefGoogle Scholar
  51. 51.
    Rhodes LE, Coleman MD, Lewis-Jones MS. Dapsone-induced motor peripheral neuropathy in pemphigus foliaceus. Clin Exp Dermatol. 1995;20:155–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Dalakas MC. Peripheral neuropathy and antiretroviral drugs. J Peripher Nerv Syst. 2001;6:14–20.PubMedCrossRefGoogle Scholar
  53. 53.
    Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 2009;8:475–90.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Wittbrodt ET. Drugs and myasthenia gravis. An update. Arch Intern Med. 1997;157:399–408.PubMedCrossRefGoogle Scholar
  55. 55.
    Hokkanen E. Antibiotics in myasthenia gravis. Br Med J. 1964;1:1111–2.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Hokkanen E. The aggravating effect of some antibiotics on the neuromuscular blockade in myasthenia gravis. Acta Neurol Scand. 1964;40:346–52.PubMedCrossRefGoogle Scholar
  57. 57.
    Jones SC, Sorbello A, Boucher RM. Fluoroquinolone-associated myasthenia gravis exacerbation: evaluation of postmarketing reports from the US FDA adverse event reporting system and a literature review. Drug Saf Int J Med Toxicol Drug Exp. 2011;34:839–47.CrossRefGoogle Scholar
  58. 58.
    Pradhan S, Pardasani V, Ramteke K. Azithromycin-induced myasthenic crisis: reversibility with calcium gluconate. Neurol India. 2009;57:352–3.PubMedCrossRefGoogle Scholar
  59. 59.
    Pijpers E, van Rijswijk RE, Takx-Köhlen B, Schrey G. A clarithromycin-induced myasthenic syndrome. Clin Infect Dis Off Publ Infect Dis Soc Am. 1996;22:175–6.CrossRefGoogle Scholar
  60. 60.
    Absher JR, Bale JF. Aggravation of myasthenia gravis by erythromycin. J Pediatr. 1991;119:155–6.PubMedCrossRefGoogle Scholar
  61. 61.
    May EF, Calvert PC. Aggravation of myasthenia gravis by erythromycin. Ann Neurol. 1990;28:577–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Argov Z, Mastaglia FL. Drug therapy: disorders of neuromuscular transmission caused by drugs. N Engl J Med. 1979;301:409–13.PubMedCrossRefGoogle Scholar
  63. 63.
    Dobrev D, Ravens U. Therapeutically relevant concentrations of neomycin selectively inhibit P-type Ca2+ channels in rat striatum. Eur J Pharmacol. 2003;461:105–11.PubMedCrossRefGoogle Scholar
  64. 64.
    Harnett MT, Chen W, Smith SM. Calcium-sensing receptor: a high-affinity presynaptic target for aminoglycoside-induced weakness. Neuropharmacology. 2009;57:502–5.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Sieb JP, Milone M, Engel AG. Effects of the quinoline derivatives quinine, quinidine, and chloroquine on neuromuscular transmission. Brain Res. 1996;712:179–89.PubMedCrossRefGoogle Scholar
  66. 66.
    Sieb JP. Fluoroquinolone antibiotics block neuromuscular transmission. Neurology. 1998;50:804–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Bertrand D, Bertrand S, Neveu E, Fernandes P. Molecular characterization of off-target activities of telithromycin: a potential role for nicotinic acetylcholine receptors. Antimicrob Agents Chemother. 2010;54:5399–402.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Shamik Bhattacharyya
    • 1
    • 2
    Email author
  • Ryan Darby
    • 1
    • 2
  • Aaron L. Berkowitz
    • 2
  1. 1.Department of NeurologyMassachusetts General HospitalBostonUSA
  2. 2.Department of NeurologyBrigham & Women’s HospitalBostonUSA

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