Case Report: Linezolid Optic Neuropathy and Proposed Evidenced-based Screening Recommendation

Dempsey, Sean P; Sickman, Amy; Slagle, William Scott

doi:10.1097/opx.0000000000001216

Cited by 15 publications

(13 citation statements)

References 6 publications

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“… 8 Cumulative incidence of reduced visual acuity was 12% at 24 months in our cohort, the earliest detected at 5 weeks after starting linezolid. This is within the range reported from other studies 7 but is likely an overestimate of true linezolid-induced optic neuropathy because visual acuity testing lacks specificity, 35 and many participants were on concomitant ethambutol which can also cause ocular toxicity. In the Nix-TB trial optic nerve disorders were suspected in 11.9% by bedside testing but confirmed optic neuropathy only occurred in 2 (<2%) participants.…”

Section: Discussionsupporting

confidence: 72%

Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study

Wasserman

Brust

Abdelwahab

et al. 2022

Journal of Antimicrobial Chemotherapy

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Background Linezolid is recommended for treating drug-resistant TB. Adverse events are a concern to prescribers but have not been systematically studied at the standard dose, and the relationship between linezolid exposure and clinical toxicity is not completely elucidated. Patients and methods We conducted an observational cohort study to describe the incidence and determinants of linezolid toxicity, and to determine a drug exposure threshold for toxicity, among patients with rifampicin-resistant TB in South Africa. Linezolid exposures were estimated from a population pharmacokinetic model. Mixed-effects modelling was used to analyse toxicity outcomes. Results One hundred and fifty-one participants, 63% HIV positive, were enrolled and followed for a median of 86 weeks. Linezolid was permanently discontinued for toxicity in 32 (21%) participants. Grade 3 or 4 linezolid-associated adverse events occurred in 21 (14%) participants. Mean haemoglobin concentrations increased with time on treatment (0.03 g/dL per week; 95% CI 0.02–0.03). Linezolid trough concentration, male sex and age (but not HIV positivity) were independently associated with a decrease in haemoglobin >2 g/dL. Trough linezolid concentration of 2.5 mg/L or higher resulted in optimal model performance to describe changing haemoglobin and treatment-emergent anaemia (adjusted OR 2.9; 95% CI 1.3–6.8). SNPs 2706A > G and 3010G > A in mitochondrial DNA were not associated with linezolid toxicity. Conclusions Permanent discontinuation of linezolid was common, but linezolid-containing therapy was associated with average improvement in toxicity measures. HIV co-infection was not independently associated with linezolid toxicity. Linezolid trough concentration of 2.5 mg/L should be evaluated as a target for therapeutic drug monitoring.

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Section: Discussionsupporting

confidence: 72%

Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study

Wasserman

Brust

Abdelwahab

et al. 2022

Journal of Antimicrobial Chemotherapy

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“…Linezolid-related optic neuropathies in patients receiving treatment for Staphylococcus aureus infections have been described ( 24 ) and can be asymptomatic or lead to reduced visual acuity, blurred vision, central scotoma, and dyschromatopsia ( 19 , 25 ). We found a high prevalence of confirmed optic neuropathy (25% of our cohort) that was fully reversible (meaning complete recovery of ophthalmologic disorder 12 months after the end of TB treatment) for only 2 of our patients after treatment withdrawal.…”

Section: Discussionmentioning

confidence: 99%

“…We found a high prevalence of confirmed optic neuropathy (25% of our cohort) that was fully reversible (meaning complete recovery of ophthalmologic disorder 12 months after the end of TB treatment) for only 2 of our patients after treatment withdrawal. We therefore suggest testing visual acuity and performing a sensory color vision test and a Goldmann visual field test before initiating linezolid with monthly checkups, as has been recently recommended ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, linezolid-associated optic neuropathy appears after 5 to 10 months of treatment for 30% of patients ( 11 , 16 ). It is still debated whether linezolid trough concentrations >2 mg/L ( 17 ) or long-term exposure could predict the occurrence of adverse effects ( 18 , 19 ). We therefore evaluated the occurrence and management of neurologic and ophthalmologic adverse effects among MDR TB patients receiving a linezolid-based treatment regimen.…”

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confidence: 99%

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Linezolid-Associated Neurologic Adverse Events in Patients with Multidrug-Resistant Tuberculosis, France

Jaspard¹,

Butel²,

Helali³

et al. 2020

Emerg. Infect. Dis.

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Linezolid is one of the most effective drugs for treating multidrug-resistant tuberculosis (MDR TB), but adverse effects remain problematic. We evaluated 57 MDR TB patients who had received > 1 dose of linezolid during 2011–2016. Overall, patients received 600 mg/day of linezolid for a median of 13 months. In 33 (58%) patients, neurologic or ophthalmologic signs developed, and 18 (32%) had confirmed peripheral neuropathy, which for 78% was irreversible at 12 months after the end of TB treatment despite linezolid withdrawal. Among the 19 patients who underwent ophthalmologic evaluation, 14 patients had optic neuropathy that fully reversed for 2. A total of 16 (33%) of 49 patients had a linezolid trough concentration >2 mg/L, and among these, 14 (88%) experienced adverse effects. No significant association was found between trough concentration and neurologic toxicity. These findings suggest the need to closely monitor patients for neurologic signs and discuss optimal duration of linezolid treatment.

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“…Optic neuropathy is another adverse event reported with extended use of linezolid. 6,19 In our study, seven patients developed optic neuropathy alone and two had both optic and peripheral neuropathy. As diagnosis of optic neuropathy is…”

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confidence: 51%

Linezolid-Associated Neuropathy in Patients with MDR/XDR Tuberculosis in Shenzhen, China

Zhang¹,

Li²,

Liu³

et al. 2022

IDR

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Linezolid is one of the key drugs for the treatment of multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB). We aimed to describe the incorporation of the Michigan Neuropathy Screening Instrument (MNSI) and serum trough concentration as screening tools for neurotoxicity in the management of MDR/XDR-TB patients receiving a linezolid-based treatment regimen in Shenzhen, China. Methods: A total of 73 patients on a linezolid-containing anti-MDR/XDR-TB regimen were prospectively enrolled. The MNSI was used for peripheral neuropathy screening. Optic neuropathy was diagnosed by ophthalmologists. Serum trough concentration was recorded and its relationship with neuropathy analyzed. Results: Of all patients, neuropathy was observed in 40% (29) during anti-TB treatment. Of these, 20 (69%) had peripheral neuritis, seven (24%) optic neuritis, and two (7%) both. Serum trough concentration >2 mg/L was observed in 17 (59%) patients with neuropathy and 13 (30%) patients without neuropathy. There was a significant statistical difference between the two groups (P=0.013). Time to onset of neuropathy from initiation of the linezolid-containing regimen was within 2 months for eight (28%) patients, 2-6 months for 18 (62%) patients, and >6 months for three (10%) patients. Sixteen (55%) patients were adjusted to a lower dose of 300 mg linezolid daily. Four (14%) patients had linezolid permanently removed from their regimen. Conclusion:Neuropathy is a commonly reported adverse event associated with long-term use of linezolid. MNSI and serum troughconcentration monitoring can be adopted as simple screening tools for early detection of neuropathy to balance linezolid efficacy and tolerability.

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Case Report: Linezolid Optic Neuropathy and Proposed Evidenced-based Screening Recommendation

Cited by 15 publications

References 6 publications

Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study

Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study

Linezolid-Associated Neurologic Adverse Events in Patients with Multidrug-Resistant Tuberculosis, France

Linezolid-Associated Neuropathy in Patients with MDR/XDR Tuberculosis in Shenzhen, China

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