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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 33  |  Issue : 3  |  Page : 344-348

Long-term linezolid: Unnerving the nerves?


Department of Ophthalmology, MGM Institute of Health Sciences, Navi Mumbai, Maharashtra, India

Date of Submission27-Jul-2020
Date of Decision10-Aug-2020
Date of Acceptance11-Aug-2020
Date of Web Publication08-Dec-2021

Correspondence Address:
Dr. Sayali Santosh Amberkar
New PG Hostel, MGM Institute of Health Sciences, Navi Mumbai - 410 209, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kjo.kjo_110_20

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  Abstract 


It is well documented that systemic antimicrobials can cause ocular side effects. This becomes especially relevant in multidrug therapy where more than one drug can cause similar ocular side effect. We describe a case of progressive decrease in vision associated with linezolid therapy in a 17-year-old female patient, on treatment with the second-line anti-tuberculous drugs including linezolid, for multiple drug-resistant tuberculosis presented to us with painless progressive decrease in vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Since the patient was not on ethambutol and gave a history of peripheral neuropathy, linezolid-induced toxic optic neuropathy was suspected and linezolid dechallenge was done. Discontinuation of linezolid treatment resulted in marked improvement in visual acuity. Our report emphasizes the need for early detection of ocular side effects and how monitoring of visual function is imperative in patients on long-term linezolid treatment.

Keywords: Linezolid, optic neuropathy, ocular side effects


How to cite this article:
Bhonsale GR, Amberkar SS. Long-term linezolid: Unnerving the nerves?. Kerala J Ophthalmol 2021;33:344-8

How to cite this URL:
Bhonsale GR, Amberkar SS. Long-term linezolid: Unnerving the nerves?. Kerala J Ophthalmol [serial online] 2021 [cited 2022 Jan 19];33:344-8. Available from: http://www.kjophthal.com/text.asp?2021/33/3/344/331912




  Introduction Top


Optic neuropathies are disorders of the optic nerve involving degeneration of the nerve. They are further classified into hereditary and acquired. Drug-induced optic neuropathy is of the toxic acquired type. Various anti-tubercular drugs are known to cause optic neuritis and optic neuropathy, the most common being ethambutol.

Linezolid, an oxazolidinone, has antibiotic activity against many important pathogens including multidrug-resistant tubercle bacillus and methicillin-resistant Staphylococcus and Streptococcus. We report a case of toxic optic neuropathy due to linezolid occurring in a patient who was on linezolid and other second-line drug therapy for multiple drug-resistant pulmonary tuberculosis (MDR-PTB). The incidence of this is not known yet.


  Case Report Top


A 17-year-old female presented to our outpatient department with painless progressive diminution of vision in both eyes for the last 15 days. Medical history was suggestive of MDR-TB on treatment with linezolid (600 mg/day), levofloxacin (750 mg/day), cycloserine (500 mg/day), ethionamide (500 mg/day), injection kanamycin (750 mg/day), clofazimine (100 mg/day), and pyridoxine (100 mg/day) for the past 6 months. All Category I drugs were discontinued in the 1st month due to resistance. On ocular examination, her distant visual acuity was counting fingers at 3 m in both eyes, not improving with pin hole, and near visual acuity was N18. Color vision was defective in both eyes (with Ishihara charts). Anterior-segment examination was unremarkable; pupils were 3 mm, round, regular, and reacting to light in both eyes (direct and indirect). There was no relative afferent pupillary defect. Both eye fundus examination revealed hyperemic disc with blurred margins [Figure 1]. Optical coherence tomography (OCT) revealed increased retinal nerve fiber layer (RNFL) thickness to 186 μm in both eyes [Figure 2]. Visual field evaluation by Humphrey field analyzer showed generalized depression in the right eye and sensory loss in the left eye corresponding to the disc edema [Figure 3] and [Figure 4]. Of all the medications the patient was on, linezolid is known to cause optic neuropathy. Further, the patient had a history of peripheral neuropathy 4 weeks before onset of ocular symptoms which was treated with oral pregabalin. The patient was diagnosed with linezolid-induced optic neuropathy. Linezolid was discontinued after opinion from the treating physician, and following that, over the next 2 weeks, the patient's unaided distant visual acuity improved to 6/9 in the right eye and 6/6 in the left eye and near visual acuity improved to N6. Color vision recovered and the patient's unaided visual acuity was restored to 6/6 for distance and N6 for near, in both eyes, after 1 month. Fundus examination revealed partial and complete resolution of right and left disc edema, respectively [Figure 5] and [Figure 6]. OCT demonstrated decrease in RNFL thickness to 159 μm in the right eye and 80 μm in the left eye [Figure 7] and the follow-up visual fields improved [Figure 8]; therefore, on the basis of Naranjo scale for adverse drug reaction, linezolid toxicity was concluded. The patient was then started on para-aminosalicylic acid granules at the advice of the physician.
Figure 1: Both eyes showing optic disc edema

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Figure 2: Optical coherence tomography retinal nerve fiber layer showing increased retinal nerve fiber layer thickness

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Figure 3: Right eye visual field showing generalized depression

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Figure 4: Left eye visual field showing minimal depression due to optic disc edema

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Figure 5: Right eye fundus photograph showing resolving optic disc edema

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Figure 6: Left eye fundus photograph showing resolved disc edema

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Figure 7: Repeat optical coherence tomography retinal nerve fiber layer showing right eye resolving optic disc edema and left eye resolved optic disc edema

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Figure 8: Repeat visual fields of both eyes showing improvement

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  Discussion Top


Optic neuropathies are disorders of the optic nerve involving degeneration of the nerve. They are further classified into hereditary and acquired. Drug-induced optic neuropathy is of the toxic acquired type. Toxic optic neuropathy has been associated with numerous compounds, including exposure to methanol, isoniazid, and ethambutol and deficiency of Vitamin B12, folate, and thiamine. It is characterized by gradual, progressive painless, bilaterally symmetric visual loss affecting central vision, and causing central or centrocecal scotoma.

MDR-TB is defined as resistance to at least rifampicin and isoniazid among the first-line anti-TB drugs. Linezolid acts by inhibiting protein synthesis and disrupting mitochondrial phosphorylation (binding to 16SrRNA) by preventing the formation of the ribosome complex that initiates it. Its unique binding site results in no cross-resistance with other drug classes; hence, linezolid is being increasingly used for the treatment of infections caused by multidrug-resistant Gram-positive bacteria. Linezolid is usually well tolerated with few adverse effects. Serious adverse reactions demanding withdrawal of the drug include myelosuppression, peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome.[1],[2],[3] Linezolid was approved by the FDA, based on the studies employing 28 days of administration.[4] There are several case reports of linezolid-induced optic or peripheral neuropathy in patients treated for a time period beyond 28 days.[5] Only two cases of toxic optic neuropathy have been reported following short-term linezolid treatment of 16 days.[6],[7] Discontinuation of linezolid therapy resulted in improvement of the optic neuropathy with significant improvement in visual acuity within 1–8 months.[8]

Fundus picture can be varied, showing temporal pallor, disc edema, or essentially normal. Complete visual recovery has been reported in all cases except one.[7] Although nearly complete recovery has been reported in most such cases, the psychological effects of bilateral drastic visual loss can be devastating, therefore best avoided by careful monitoring and discontinuation of drug if needed. The most common indication for long-term linezolid therapy has been infection with methicillin-resistant Staphylococcus aureus Scientific Name Search  but in our case, optic neuropathy occurred after using linezolid for 6 months at a dose of 600 mg per day for infection with Mycobacterium tuberculosis. Since our patient had a history of preceding peripheral neuropathy and her vision improved only after withdrawal of linezolid, she was diagnosed with linezolid-induced toxic neuropathy. There are limited data available regarding the efficacy and safety of linezolid in multidrug-resistant TB since it is always administered as part of combination therapy, but the recent PMDT guidelines, 2019 state it as a Group A drug in the treatment of MDR-TB.


  Conclusion Top


With increasing emergence of MDR-TB, for which the treatment options are limited, physicians are compelled to resort to new drug therapies. Although ethambutol is the most common anti-tubercular drug implicated to cause toxic optic neuropathy, it is important to be aware that if patient is not on ethambutol, one must consider other drugs notorious for the same. With our country being rampantly affected with drug-resistant TB, where multiple drug therapy is the only option, this is even more a demand for being vigilant of side effects such as peripheral and optic neuropathy. Ophthalmologists and physicians must be aware that strict and regular monitoring of visual function is imperative in patients on long-term linezolid therapy. Also note that peripheral neuropathy should be recognized as an early sign of toxicity and due course of action must be taken to avoid the optic neuropathy which may follow, if linezolid is continued.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Narita M, Tsuji BT, Yu VL. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy 2007;27:1189-97.  Back to cited text no. 1
    
2.
Bressler AM, Zimmer SM, Gilmore JL, Somani J. Peripheral neuropathy associated with prolonged use of linezolid. Lancet Infect Dis 2004;4:528-31.  Back to cited text no. 2
    
3.
Migliori GB, Eker B, Richardson MD, Sotgiu G, Zellweger JP, Skrahina A, et al. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis. Eur Respir J 2009;34:387-93.  Back to cited text no. 3
    
4.
Birmingham MC, Rayner CR, Meagher AK, Flavin SM, Batts DH, Schentag JJ. Linezolid for the treatment of multidrug-resistant, Gram-positive infections: Experience from a compassionate-use program. Clin Infect Dis 2003;36:159-68.  Back to cited text no. 4
    
5.
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.  Back to cited text no. 5
    
6.
Azamfirei L, Copotoiu SM, 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;16:402-4.  Back to cited text no. 6
    
7.
Joshi L, Taylor SR, 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:e73-4.  Back to cited text no. 7
    
8.
Lee E, Burger S, Shah J, Melton C, Mullen M, Warren F, et al. Linezolid-associated toxic optic neuropathy: A report of 2 cases. Clin Infect Dis 2003;37:1389-91.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]



 

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