The absolute risk with current oral fluoroquinolone exposure was 2.4 (95% CI, 1.8-3.1) per 10000 patients per year of current use. All rights reserved. One of the most common causes is diabetes. J Neuroophthalmol 2014;34(3):257-8. Nguyen GH, Guo EL, Norris D. A rare case of erythema elevatum diutinum presenting as diffuse neuropathy. A meta-analysis of available data from multiple registries found neuropathy and anemia to be the most common toxicities; overall neuropathy occurred in 31% on chronic therapy (97). The incidence of optic neuropathy in 84 patients treated with ethambutol. swelling of the feet or lower legs. Heckmann JG, Dutsch M, Schwab S. Linezolid-associated small-fiber neuropathy. A Swedish paper describes 37 patients who reported sensory disturbances to an adverse drug reaction advisory committee after having taken fluoroquinolones; over 80% described paresthesias and half described numbness; in the majority of cases, symptoms occurred within one week of starting treatment and resolved within 2 weeks after stopping the drug (39). Isolated case reports continue to be uncovered. information and will only use or disclose that information as set forth in our notice of In this article, the author discusses antibiotics that have been associated with peripheral neuropathy, focusing on those in general use and with the most established associations, and detailing the possible underlying pathophysiologic mechanisms leading to neuropathy. All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias. Takeuchi H, Takahashi M, Kang J, et al. A 60-year-old woman developed severe axonal neuropathy after starting nitrofurantoin; superficial radial nerve biopsy demonstrated vasculitis (01). Boston: Butterworth-Heinemann, 2000:2045-130. The drug caused loss of neurons, myelin, and increased autophagy indicators in a rat model and suppression of Schwann cells in an in vitro model (96). Any use of this site constitutes your agreement to the Terms and Conditions and Privacy Policy linked below. Waldinger TP, Siegle RJ, Weber W, Voorhees JJ. A distal pansensory neuropathy characterized by pain, burning paresthesias, and dysesthesias in the feet and hands is typical. Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press. Physician reports in medicolegal journals highlight the contentious and typically anecdotal evidence (25). Med Lett Drugs Ther 2013;55(1429):89. Isoniazid causes a predominantly sensory, predominantly large-fiber symmetric axonal peripheral neuropathy (15). A rare but well-characterized, primarily motor axonal neuropathy may develop (37; 69). A systematic review of dysglycemic and neuropathic effects of fluoroquinolones. Drug-Induced Neurological Disorders. J Peripher Nerv Syst 2008;13(2):157-8. Peripheral neuropathy is the most common form of diabetic neuropathy. Doxycycline / adverse effects*. include protected health information. Slow acetylators are at increased risk for peripheral neuropathy due to isoniazid and dapsone. Prolonged linezolid treatment induced a mild, predominantly small sensory fiber neuropathy in mice (08). Side effects can include drowsiness and dizziness. Topical treatments. Capsaicin cream, which contains a substance found in hot peppers, can cause modest improvements in peripheral neuropathy symptoms. You might have skin burning and irritation where you apply the cream, but this usually lessens over time. They concluded that further research was needed for this suspected association. Peripheral neuropathy has long been recognised as a potential side effect of fluoroquinolone antibiotics but it was not known how strong this association was and how it could be affected by the length of treatment, or by age and gender. Onset may be insidious, subacute, or acute, and symptoms typically progress if the antibiotic is continued. Linezolid-associated peripheral neuropathy. Peripheral neuropathy, a result of damage to the nerves located outside of the brain and spinal cord (peripheral nerves), often causes weakness, numbness and pain, usually in the hands and feet. Data analyses were conducted January 8, 2018. https://www.foundationforpn.org/what-is-peripheral-neuropathy/evaluation-and-tests/. Neurotoxicology 1979;1:299. Adults with incident peripheral neuropathy were matched (on age, sex, general practice, and calendar time) with up to 4 controls by using incidence density sampling selected from a cohort prescribed oral fluoroquinolone or amoxicillin-clavulanate antibiotics. Optic neuropathy is more common, occurring in as many as 10% of patients treated for pulmonary tuberculosis (19). Neurology 2006;66(4):595-8. Philadelphia, Pa.: Elsevier; 2018. https://www.clinicalkey.com. J Neurol Sci 2001;192:71-80. Analysis of the AERS data also found that development of Guillain-Barr syndrome and fluoroquinolones exposure, using an Empirical Bayes Geometric Mean disproportionality measure, was twice as likely (02). Bobylev I, Maru H, Joshi AR, Lehmann HC. Linezolid. It has been postulated that neurotoxicity may be due to a dose-dependent depletion of glutathione (79). An official website of the United States government. Experimental ethambutol neuropathy in rats. Conclusions and Relevance The results of the present study suggested that oral fluoroquinolone therapy was associated with an increased risk of incident peripheral neuropathy that may depend on the timing of the exposure and the cumulative dose. Schecter GF, Scott C, True L, Raftery A, Flood J, Mase S. Linezolid in the treatment of multidrug-resistant tuberculosis. Pharmacotherapy 2007;27(8):1189-97. 4th ed. Patients typically show complete clinical recovery, but this may be slow because it requires axonal regeneration and sprouting, and some show coasting, or clinical progression, after the drug is discontinued (44; 69). Rev Neurol (Paris) 1986;142:746-52. Arch Neurol 2012;69(2):265-8. Nitrofurantoin. Ghosh R, Chatterjee S, Dubey MJ, Dubey S, Benito-Len J. Metronidazole-induced toxic neuropathy with the "Boomerang" sign: a case report. Am J Ther 2016;23(6):e1839-e1841. Rho JP, Sia IG, Crum BA, Dekutoski MB, Trousdale RT. Considering the rarity of antibiotic-induced peripheral neuropathy, it is in generally prudent to consider other causes of axonal polyneuropathy, although the temporal relationship to administration of the drug and improvement with discontinuation should be helpful. J Clin Invest 1981;67(1):37-41. In some cases, as with isoniazid, recovery can be slow and incomplete, especially after prolonged use. Nanyonga SM, Kitutu FE, Kalyango J, Frank M, Kiguba R. High burden of adverse drug reactions to Isoniazid Preventive Therapy in people living with HIV at three tertiary hospitals in Uganda: associated factors. Risk increased by approximately 3% for each additional day of current fluoroquinolone exposure and persisted for up to 180 days following exposure. Careers. A conditional logistic regression model was used to estimate relative risk. Carpal tunnel syndrome is an example of mononeuropathy. Chloroquine myopathy and neuropathy with elevated CSF protein. Novak P, Felsenstein D, Mao C, Octavien NR, Zubcevik N. PLoS One. Grgurevi I, Marusi S, Bani M, Buljevac M, Crncevic-Urek M, Cabrijan Z, Kardumz D, Kujundzi M, Lesnjakovi I, Tadi M, Loncar B. Lijec Vjesn. Acquired peripheral neuropathy causes include: Physical injury (trauma), such as injury from automobile accidents, falls, sports, and medical procedures that can Main Outcomes and Measures Incident peripheral neuropathy cases recorded in electronic medical records. sharing sensitive information, make sure youre on a federal Drug-resistant leprosy strains emerged in India but only about 2% to 3% of strains are dapsone resistant (50). Comparative neurological safety of fluoroquinolones versus therapeutic alternatives. Case reports previously identified peripheral neuropathy as a potential side effect of treatment with fluoroquinolone antibiotics. What is neurology? Medication-induced peripheral neuropathy. Other postulated mechanisms include impaired membrane transport and inhibition of protein synthesis (51). Health care professionals should consider these potential risks when prescribing fluoroquinolone antibiotics. A mild, predominantly sensory peripheral neuropathy is seen in as many as 4% of patients (84). Chloroquine neuromyopathies: 4 cases during antimalarial prevention. After drug cessation the neuropathy stabilized and vision partially improved. Nabity SA, Gunde LJ, Surie D, et al. With some notable exceptions, these toxic effects are rare compared to the relatively high incidence of neuropathy associated with antiretroviral drugs and antineoplastic agents. However, excessive pyridoxine exposure can independently cause sensory neuropathy. Neuroscience research articles are provided. Several antibiotics are associated with peripheral neuropathy. With some notable exceptions, these toxic effects are rare compared to the relatively high incidence of neuropathy associated with antiretroviral drugs and antineoplastic agents. Prolonged thiamphenicol treatment associated sensory axonal polyneuropathy. It is also under study as an antineoplastic drug for the treatment of hormone-refractory or metastatic prostate cancer. Cureus 2022;14(10):e30889. Peripheral neuropathy due to nitrofurantoin. Loughridge LW. Their cohort contained 976,568 individuals exposed to a fluoroquinolone antibiotic matched 1:1 with a comparator antibiotic for common infections. The risk of toxic optic neuropathy is increased in patients carrying mutation in the optic atrophy 1 (OPA1) gene, possibly through a mitochondrial toxicity mechanism (35). It has no systemic antibacterial effect because its activity depends on its being concentrated in the urine; it is, therefore, ineffective in renal failure. government site. Accessed April 2, 2019. Shen B, Achkar JP, Lashner BA, et al. eCollection 2019. The peripheral nerves also send sensory information to the central nervous system. Fluoroquinolones are broad-spectrum antibiotics that prevent DNA recoiling after replication by inhibiting DNA gyrase. Arch Psychiatr Nervenkr 1982;232(1):63-9. It works by an unknown but specific mechanism. Additionally, isoniazid is acetylated in the liver by N-acetyltransferase, and those who carry mutations in N-acetyltransferase leading to slow acetylation are at increased risk for neuropathy (31). J Clin Neuromuscul Dis 2022;24(2):85-94. Morphological changes, such as clustered terminal nerve swellings, in skin biopsy samples demonstrated support of 2 cases of clinical nitrofurantoin-induced neuropathy despite normal sensory and motor nerve conduction studies (87). Carelli V, Ross-Cisneros FN, Sadun AA. Genetics articles related to neuroscience research will be listed here. Recovery is rapid if the problem is detected early but may be slow and incomplete if the cause remains unrecognized. Listen to MedLink on the go with Audio versions of each article. They are used extensively for a wide range of bacterial infections, and are especially useful for gram-negative meningitis. 3rd edition. HIV-infected patients are at increased neuropathy risk prior to initiation of treatment if they were treated for tuberculosis; in a study, many were pyridoxine deficient (89). J Neurol Sci 1981;51:89-99. Interestingly, this mutation also affects mitochondrial function, namely mitochondrial fusion. Older men, Chemotherapy-induced peripheral neuropathy. Please enable it to take advantage of the complete set of features! official website and that any information you provide is encrypted information highlighted below and resubmit the form. Childhood Degenerative & Metabolic Disorders, News releases, announcements, interviews and other supplemental content of neurologic interest, Stay informed with the latest news in neurology and neuroscience, Featuring clinician-investigators who have made extraordinary contributions to neurology, Meet some of the expert physicians who serve as, Listen to clinical cases and topical reviews in neurology. PLoS One 2021;16(4):e0248115. Koh WJ, Kwon OJ, Gwak H, et al. Estes ML, Ewing-Wilson D, Chou SM, et al. A 69-year-old woman treated with a total of 55 g of metronidazole for diverticular disease and a 52-year-old man with a protracted metronidazole course for a hepatic abscess (cumulative dose 168 g) developed peripheral neuropathy (36). Painful neuropathy with skin denervation after prolonged use of linezolid. Treatment of diabetic neuropathy. If peripheral neuropathy causes you to lose feeling in your feet, you may not notice pressure or injuries that lead to blisters and sores. Vibration and proprioception senses are severely affected (98). Int J Tuberc Lung Dis 2015;19(11):1312-9. privacy practices. Ann Intern Med 1992;117:1058-9. Oral fluoroquinolone exposure was associated with an increased relative incidence of peripheral neuropathy compared with nonexposure (adjusted incident rate ratio, 1.47; 95% CI, 1.13-1.92); amoxicillin-clavulanate exposure had no increased risk. Singh B, Cocker D, Ryan H, Sloan DJ. Primary axonal injury is suggested by electrophysiologic studies, although segmental demyelination and remyelination has been reported (84). Suramin induced ceramide accumulation leads to apoptotic cell death in dorsal root ganglion neurons. Weimer LH. Often, paresthesias are the first noticeable symptoms. Occasionally, numbness can have a burning quality that can be severe. We hate spam and only use your email to contact you about newsletters. In rats given 150 mg/kg/day of ethambutol for 9 months, teased fiber analysis of lower extremity nerves showed extensive axonal degeneration and regeneration, suggesting that axonal degeneration may be primary (52). You may need treatment to increase your blood pressure or, in rare cases, a pacemaker. A case noting reversibility is also reported (90). Ellis DE, Hubbard RA, Willis AW, et al. Early diagnosis and treatment offer the best chance for controlling your symptoms and preventing further damage to your peripheral nerves. Stevenson MA, Calderwood SK, Coleman CN. It binds to the 50S ribosomal subunit and prevents the formation of the initiation complex required to translate mRNA into protein. Diabetes can make these wounds difficult to heal and increase the chance of infections. Feb. 10, 2021. Neuromuscular toxicity from short-term use of hydroxychloroquine or this agent against COVID19 is speculative at present. Your peripheral nervous system sends information from your brain and spinal cord (central nervous system) to the rest of your body. The decision was based on reports from the FDAs Adverse Event Reporting System (AERS) database that serves the important function of post-marketing safety surveillance. This review will cover antimicrobials that are in more general use and those with well-established associations. They worked very well in healing my infections but I was left with stabbing, exploding pains in my feet, mostly my toes. Symptoms typically occur after several months of treatment (31). Nerves are classified into: Signs and symptoms of peripheral neuropathy might include: If autonomic nerves are affected, signs and symptoms might include: Peripheral neuropathy can affect one nerve (mononeuropathy), two or more nerves in different areas (multiple mononeuropathy), or many nerves (polyneuropathy). 4,11,25 Parenteral IV antibiotic therapy, if needed, can be done. It typically occurs many years after drug use, and with doses greater than 300 mg/day (92). The agent is intended to prevent latent tuberculosis reactivation. Patients develop progressive muscle weakness and wasting in distal muscles of the extremities, especially in the hands. Cochrane Database Syst Rev 2019;3:CD012836. Fluoroquinolone-induced serious, persistent, multisymptom adverse effects. Besides medications used to treat conditions associated with peripheral neuropathy, medications used to relieve peripheral neuropathy signs and symptoms Tendinopathy is a well reported treatment complication that may have overlapping symptoms. HHS Vulnerability Disclosure, Help Of multidrug-resistant tuberculosis of the complete set of features and those with well-established associations ;! Erythema elevatum diutinum presenting as diffuse neuropathy peripheral neuropathy ( 15 ) PLoS One ;. Neurotoxicity may be slow and incomplete, especially after prolonged use of this site your... 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Improvements in peripheral neuropathy is more common, occurring in as many as %., Voorhees JJ isoniazid, recovery can be done previously identified peripheral neuropathy is more common, occurring in many! Joshi AR, Lehmann HC EL, Norris D. a rare case of erythema diutinum. % for each additional day of current fluoroquinolone exposure and persisted for up to days... ( 84 ), Schwab S. Linezolid-associated small-fiber neuropathy muscle weakness and wasting in muscles... Cream, which contains a substance found in hot peppers, can cause modest improvements in peripheral neuropathy is most.