ABSTRACT Purpose: To report a rare toxic optic neuropathy after long-term use of two medications: ethambutol and linezolid. Case report: A 65-year-old man presented to the Miami Veterans Affairs Medical Center in December 2014 for evaluation of progressive vision decrease in both eyes. The patient presented with best-corrected visual acuities of 20/400 in the right eye and counting fingers at 5 feet in the left eye. Color vision was significantly reduced in both eyes. Visual fields revealed a cecocentral defect in both eyes. His fundus and optic nerve examination was unremarkable. Because vision continued to decline after discontinuation of ethambutol, linezolid was also discontinued, after which vision, color vision, and visual fields improved. Because of these findings, the final diagnosis was toxic optic neuropathy. Final visual outcome was 20/30 in the right eye and 20/40 in the left eye. Conclusions: Drug-associated toxic optic neuropathy is a rare but vision-threatening condition. Diagnosis is made based on an extensive case history and careful clinical examination. The examination findings include varying decrease in vision, normal pupils and extraocular muscles, and unremarkable fundoscopy, with the possibility of swollen optic discs in the acute stage of the optic neuropathy. Other important findings descriptive of toxic optic neuropathy include decreased color vision and cecocentral visual field defects. This case illustrates the importance of knowledge of all medications and/or substances a patient consumes that may cause a toxic reaction and discontinuing them immediately if the visual functions are worsening or not improving.
JOSEA,ANTHONYC,ROBERTN,et al.Safety of long-term use of linezolid:results of an open-label study[J].Ther Clin Risk Manag,2016,12:1347-1354.
The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50–254 days). In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs) included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk, and central scotomas in each eye. In our small population, linezolid was generally well tolerated and AEs were consistent with the known safety profile. Extensive ophthalmologic testing of all 24 linezolid-treated patients identified one case adjudicated as probable, linezolid-associated optic neuropathy.
KATSUJIK,MIKIM,CHIEMIK,et al.Linezolid-associated optic neuropathy in a patient with ocular sarcoidosis[J].Jpn J Ophthalmol,2009,53(4):420-424.
We describe a case of bilateral linezolid-associated optic neuropathy in a patient with ocular sarcoidosis.A 70-year-old woman with sarcoidosis noted foggy vision in both eyes. Best-corrected visual acuity was 0.5 in the right eye and 0.9 in the left. No abnormality other than slight optic disc hyperemia was visible in either eye. A central scotoma in both eyes and enlargement of the blind spot in the right eye were detected by Goldmann perimetry examination, and magnetic resonance imaging demonstrated an edematous optic nerve in the right eye. Therefore, retrobulbar optic neuritis resulting from sarcoidosis was initially suspected. Sub-Tenon's capsule injection of triamcinolone acetonide along with steroid pulse therapy was given; however, best-corrected visual acuity worsened to 0.06 in the right eye and 0.08 in the left. Pulse therapy was discontinued on day 1, and the possibility of linezolid-associated optic neuropathy was speculated because linezolid had been given for methicillin-resistant Staphylococcus aureus osteomyelitis 2 years before by an orthopedist. After discontinuation of linezolid, best-corrected visual acuity improved to 0.8 in the right eye and 0.9 in the left, and the optic disc hyperemia in both eyes disappeared.Our findings demonstrate that it is important for ophthalmologists as well as physicians and orthopedists to consider the possibility of optic neuropathy caused by long-term use of linezolid.
STEVENH,RODF.Optic neuropathy associated with linezolid treatment[J].J Neuro Ophthalmol,2005,25(1):18-21.
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LEONARDA,SANDA-MARIAC,KLARAB,et al.Complete blindness after optic neuropathy induced by short-term linezolid treatment in a patient suffering from muscle dystrophy[J].Pharmacoepidem DR S,2007,16(4):402-404.
We present a case of severe optic neuropathy following linezolid treatment, which led to complete irreversible blindness, in a patient with progressive muscular dystrophy, treated with linezolid for 16 days for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Interruption of antibiotic therapy did not lead to remission of ocular symptoms. Administration of linezolid may lead to severe neuropathy even in the case of short-term treatment. Copyright 2006 John Wiley & Sons, Ltd.
LAVNISHJ,SIMON R J T,OLIVER L,et al.A Case of optic neuropathy after short-term linezolid use in a patient with acute lymphocytic leukemia[J].Clin Infect Dis,2009,48(7):73-74.
Abstract A patient undergoing chemotherapy for treatment of acute lymphocytic leukemia developed septicemia that was treated with linezolid for 16 days. The patient subsequently reported reduced vision in both eyes and was found to have bilateral optic neuropathy. After the discontinuation of linezolid treatment, both the optic neuropathy and visual impairment resolved without sequelae.
HABIBG,HOENB,TORNOSP,et al.Guidelines on the prevention,diagnosis,and treatment of infective endocarditis (new version 2009):the task force on the prevention,diagnosis,and treatment of infective endocarditis of the European Society of Cardiology (ESC).Endorsed by the european society of clinical microbiology and infectious diseases (ESCMID) and the international society of chemotherapy (ISC) for infection and cancer[J].Eur Heart J,2009,30(19):2369-2413.
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GOULD FK,DENNING DW,ELLIOTT TS,et al.Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults:a report of the Working Party of the British Society for Antimicrobial Chemotherapy[J].J Antimicrob Chemother,2012,67(2):269-289.
The BSAC guidelines on treatment of infectious (IE) were last published in 2004. The guidelines presented here have been updated and extended to reflect developments in diagnostics, new trial data and the availability of new antibiotics. The aim of these guidelines, which cover both native valve and , is to standardize the initial investigation and treatment of IE. An extensive review of the literature using a number of different search criteria has been carried out and cited publications used to support any changes we have made to the existing guidelines. Publications referring to in vitro or animal models have only been cited if appropriate clinical data are not available. Randomized, controlled trials suitable for the development of evidenced-based guidelines in this area are still lacking and therefore a consensus approach has again been adopted for most recommendations; however, we have attempted to grade the evidence, where possible. The guidelines have also been extended by the inclusion of sections on clinical diagnosis, echocardiography and surgery.
LAURIDSENT,BRUUNL,RASMUSSENR,et al.Linezolid as rescue treatment for left-sided infective endocarditis:an observational,retrospective,multicenter study[J].Eur J Clin Microbiol Infect Dis,2012,31(10):2567-2574.
The increasing number of resistant bacterial strains in infective endocarditis (IE) emphasizes the need for a constant development of antimicrobials. Linezolid is an oxazolidinone with an effect on Gram-positive cocci. Only a few casuistic reports describe its utilization in the treatment of IE. The objective of this study is to report our experience with linezolid from a large consecutive cohort of IE patients. In a retrospective cohort study, data on 550 consecutive IE patients were collected at two tertiary University Hospitals in Copenhagen, Denmark. The main endpoints were differences in the in-hospital and 12 months post-discharge mortality between IE patients receiving linezolid for a part of the treatment and IE patients receiving conventional treatment. Of the 550 patients enrolled in the study, 38 patients received linezolid treatment and 512 received conventional treatment. Reasons for adding linezolid were antibiotic intolerance ( n 65=6513), nephrotoxicity ( n 65=655), pharmaceutical interactions ( n 65=651), inadequate clinical response ( n 65=6514), or inadequate microbial response ( n 65=655). No significant differences in the cure rate (7402% vs. 7102%, p > 0.05), in-hospital mortality (1302% vs. 1402%, p 65>650.05), or post-discharge mortality at 1202months follow-up (2602% vs. 2602%, p > 0.05) were observed. In the current study, we found that linezolid, in general, was well tolerated and associated with the same outcome as in patients with Gram-positive IE treated with other antibiotics.
There is a group of optic neuropathies of either genetic or acquired origin characterized by similar clinical manifestations with preferential involvement of the papillomacular bundle (PMB). PMB fibers are most susceptible to injury as they are small, unmyelinated, and have high-energy demands. These optic neuropathies share a presumed common pathophysiology of mitochondrial dysfunction. A variety of medications cause optic neuropathy by interfering with mitochondrial function. The evidence linking these therapeutic agents as a cause of mitochondrial optic neuropathy (MON) is well established in some and less certain in others. The differential diagnosis includes other optic nerve disorders producing bilateral, symmetric visual loss, including certain nutritional deficiencies, toxins, and genetic diseases. Ethambutol, chloramphenicol, linezolid, erythromycin, streptomycin, and antiretroviral drugs can cause drug-related MON. In many cases, drug toxicity is dose and duration dependent, and discontinuation of the drug in a timely manner can lead to significant visual recovery. Mitochondrial optic neuropathies are increasingly recognized as a spectrum of conditions that reach a similar end point by compromising a common pathway of mitochondrial dysfunction. Clinicians should be aware of drugs that can cause a MON. Prompt recognition of this association is critical in preventing irreversible, profound visual loss.
Guidelines on the prevention,diagnosis,and treatment of infective endocarditis (new version 2009):the task force on the prevention,diagnosis,and treatment of infective endocarditis of the European Society of Cardiology (ESC).Endorsed by the european society of clinical microbiology and infectious diseases (ESCMID) and the international society of chemotherapy (ISC) for infection and cancer
Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults:a report of the Working Party of the British Society for Antimicrobial Chemotherapy
, 冯赵慧子
