title: Potential for linezolid-related blindness: a review of spontaneous adverse event reports.
abstract: OBJECTIVE
  To provide clinicians with an understanding of the comparative occurrence of linezolid and blindness, and to provide any clinically relevant characteristics that may be useful in identifying the patients at risk.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Spontaneous reports in the United States Food and Drug Administration Adverse Event Reporting System (AERS) database generated between November 1, 1997, and December 21, 2008.
  
  
  METHODS
  Twenty-nine patients who experienced blindness while receiving linezolid therapy.
  
  
  RESULTS
  Available information related to each case of linezolid-reported blindness in the AERS database was qualitatively and quantitatively reviewed. Optic nerve disorders, glaucoma, and treatment with linezolid for long durations were common characteristics in patients experiencing blindness. A limitation of AERS is the lack of a quantitative exposure estimate to put rare adverse events of the AERS, such as linezolid-related blindness, into perspective. To overcome this limitation, disproportionality analysis with Bayesian correction methodology was used. Disproportionality analysis uses an adverse event relative reporting ratio (RRR) to compare the occurrence of a specific adverse event with an index drug of interest to the occurrence of the same adverse event with similar agents or with all other FDA-approved prescription drugs. The disproportionality analysis was considered meaningful if the 5th percentile of the distribution of the RRR (RRR(05)) was 2 or greater. Among the 29 reported cases of linezolid use and blindness, an RRR(05) of 2.1 was determined for linezolid-related blindness compared with all other agents listed in the AERS. Also, RRR(05) values of 2.7 and 2.2 were found when linezolid was compared with all other systemic antibiotics and a select subgroup of antibiotics, respectively.
  
  
  CONCLUSIONS
  Although disproportionality analyses suggested a quantitative signal for an association between linezolid use and blindness, causality cannot be inferred from the data. Thus, additional rigorous scientific analyses are warranted to explore these findings.
authors.affiliation: School of Pharmacy and Pharmaceutical Science, University at Buffalo, Buffalo, New York, USA. JB322@buffalo.edu
authors.forename: Jack
authors.initials: J
authors.lastname: Brown
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Aitken
authors.forename: Robbert P
authors.initials: RP
authors.lastname: van Manen
mesh_terms: D000081:Acetamides / Q000009:adverse effects*; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000009:adverse effects*; D001499:Bayes Theorem; D001766:Blindness / Q000209:etiology*; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D005901:Glaucoma / Q000150:complications; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D009901:Optic Nerve Diseases / Q000150:complications; D023303:Oxazolidinones / Q000009:adverse effects*; D012189:Retrospective Studies; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid