Abstract
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.
Similar content being viewed by others
References
Frytak S, Moertel CH, Childs DS. Neurologic toxicity associated with high-dose metronidazole therapy. Ann Intern Med. 1978;88:361–2.
Maw G, Aitken P. Isoniazid overdose: a case series, literature review and survey of antidote availability. Clin Drug Investig. 2003;23:479–85.
Grøndahl TO, Langmoen IA. Epileptogenic effect of antibiotic drugs. J Neurosurg. 1993;78:938–43.
Lode H. Potential interactions of the extended-spectrum fluoroquinolones with the CNS. Drug Saf Int J Med Toxicol Drug Exp. 1999;21:123–35.
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.
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.
Yagawa K. Latest industry information on the safety profile of levofloxacin in Japan. Chemotherapy. 2001;47 Suppl 3:38–43. discussion 44–48.
Moellering Jr RC, Eliopoulos GM, Sentochnik DE. The carbapenems: new broad spectrum beta-lactam antibiotics. J Antimicrob Chemother. 1989;24(Suppl A):1–7.
Cannon JP, Lee TA, Clark NM, Setlak P, Grim SA. The risk of seizures among the carbapenems: a meta-analysis. J Antimicrob Chemother 2014
Schliamser SE, Cars O, Norrby SR. Neurotoxicity of beta-lactam antibiotics: predisposing factors and pathogenesis. J Antimicrob Chemother. 1991;27:405–25.
Lerner PI, Smith H, Weinstein L. Penicillin neurotoxicity. Ann N Y Acad Sci. 1967;145:310–8.
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 2013
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.
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.
Mancl EE, Gidal BE. The effect of carbapenem antibiotics on plasma concentrations of valproic acid. Ann Pharmacother. 2009;43:2082–7.
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.
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.
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.
O’Connor NK, Fris J. Clarithromycin-carbamazepine interaction in a clinical setting. J Am Board Fam Pract. 1994;7:489–92.
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.
Block SH. Carbamazepine-isoniazid interaction. Pediatrics. 1982;69:494–5.
Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis and treatment. Crit Care Clin. 2008;24:657–722. vii.
Bischoff A, Meier C, Roth F. Gentamicin neurotoxicity (polyneuropathy–encephalopathy). Schweiz Med Wochenschr. 1977;107:3–8.
Fletcher J, Aykroyd LE, Feucht EC, Curtis JM. Early onset probable linezolid-induced encephalopathy. J Neurol. 2010;257:433–5.
Saidinejad M, Ewald MB, Shannon MW. Transient psychosis in an immune-competent patient after oral trimethoprim-sulfamethoxazole administration. Pediatrics. 2005;115:e739–741.
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.
Grill MF, Maganti RK. Neurotoxic effects associated with antibiotic use: management considerations. Br J Clin Pharmacol. 2011;72:381–93.
Kuriyama A, Jackson JL, Doi A, Kamiya T. Metronidazole-induced central nervous system toxicity: a systematic review. Clin Neuropharmacol. 2011;34:241–7.
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.
Sharma P, Sharma R. Toxic optic neuropathy. Indian J Ophthalmol. 2011;59:137–41.
Melamud A, Kosmorsky GS, Lee MS. Ocular ethambutol toxicity. Mayo Clin Proc. 2003;78:1409–11.
Samarakoon N, Harrisberg B, Ell J. Ciprofloxacin-induced toxic optic neuropathy. Clin Exp Ophthalmol. 2007;35:102–4.
Das S, Mondal S. Oral levofloxacin-induced optic neuritis progressing in loss of vision. Ther Drug Monit. 2012;34:124–5.
Godel V, Nemet P, Lazar M. Chloramphenicol optic neuropathy. Arch Ophthalmol. 1980;98:1417–21.
McGrath NM, Kent-Smith B, Sharp DM. Reversible optic neuropathy due to metronidazole. Clin Exp Ophthalmol. 2007;35:585–6.
Van Stavern GP. Metabolic, hereditary, traumatic, and neoplastic optic neuropathies. Continuum (Minneap Minn). 2014;20:877–906.
Lessell S. Histopathology of experimental ethambutol intoxication. Invest Ophthalmol Vis Sci. 1976;15:765–9.
Choi SY, Hwang JM. Optic neuropathy associated with ethambutol in Koreans. Korean J Ophthalmol. 1997;11:106–10.
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.
Rucker JC, Hamilton SR, Bardenstein D, Isada CM, Lee MS. Linezolid-associated toxic optic neuropathy. Neurology. 2006;66:595–8.
Weimer LH, Sachdev N. Update on medication-induced peripheral neuropathy. Curr Neurol Neurosci Rep. 2009;9:69–75.
Manji H. Drug-induced neuropathies. Handb Clin Neurol. 2013;115:729–42.
Pratt RW, Weimer LH. Medication and toxin-induced peripheral neuropathy. Semin Neurol. 2005;25:204–16.
Hobson-Webb LD, Roach ES, Donofrio PD. Metronidazole: newly recognized cause of autonomic neuropathy. J Child Neurol. 2006;21:429–31.
Saqueton AC, Lorincz AL, Vick NA, Hamer RD. Dapsone and peripheral motor neuropathy. Arch Dermatol. 1969;100:214–7.
Narita M, Tsuji BT, Yu VL. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy. 2007;27:1189–97.
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.
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.
Boyce EG, Cookson ET, Bond WS. Persistent metronidazole-induced peripheral neuropathy. DICP Ann Pharmacother. 1990;24:19–21.
Bressler AM, Zimmer SM, Gilmore JL, Somani J. Peripheral neuropathy associated with prolonged use of linezolid. Lancet Infect Dis. 2004;4:528–31.
Rhodes LE, Coleman MD, Lewis-Jones MS. Dapsone-induced motor peripheral neuropathy in pemphigus foliaceus. Clin Exp Dermatol. 1995;20:155–6.
Dalakas MC. Peripheral neuropathy and antiretroviral drugs. J Peripher Nerv Syst. 2001;6:14–20.
Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 2009;8:475–90.
Wittbrodt ET. Drugs and myasthenia gravis. An update. Arch Intern Med. 1997;157:399–408.
Hokkanen E. Antibiotics in myasthenia gravis. Br Med J. 1964;1:1111–2.
Hokkanen E. The aggravating effect of some antibiotics on the neuromuscular blockade in myasthenia gravis. Acta Neurol Scand. 1964;40:346–52.
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.
Pradhan S, Pardasani V, Ramteke K. Azithromycin-induced myasthenic crisis: reversibility with calcium gluconate. Neurol India. 2009;57:352–3.
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.
Absher JR, Bale JF. Aggravation of myasthenia gravis by erythromycin. J Pediatr. 1991;119:155–6.
May EF, Calvert PC. Aggravation of myasthenia gravis by erythromycin. Ann Neurol. 1990;28:577–9.
Argov Z, Mastaglia FL. Drug therapy: disorders of neuromuscular transmission caused by drugs. N Engl J Med. 1979;301:409–13.
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.
Harnett MT, Chen W, Smith SM. Calcium-sensing receptor: a high-affinity presynaptic target for aminoglycoside-induced weakness. Neuropharmacology. 2009;57:502–5.
Sieb JP, Milone M, Engel AG. Effects of the quinoline derivatives quinine, quinidine, and chloroquine on neuromuscular transmission. Brain Res. 1996;712:179–89.
Sieb JP. Fluoroquinolone antibiotics block neuromuscular transmission. Neurology. 1998;50:804–7.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Shamik Bhattacharyya and Ryan Darby contributed equally to the work.
This article is part of the Topical Collection on Central Nervous System Infections
Rights and permissions
About this article
Cite this article
Bhattacharyya, S., Darby, R. & Berkowitz, A.L. Antibiotic-Induced Neurotoxicity. Curr Infect Dis Rep 16, 448 (2014). https://doi.org/10.1007/s11908-014-0448-3
Published:
DOI: https://doi.org/10.1007/s11908-014-0448-3