title: Streptococcus endophthalmitis outbreak after intravitreal injection of bevacizumab: one-year outcomes and investigative results.
abstract: OBJECTIVE
  To report the 1-year clinical outcomes of an outbreak of Streptococcus endophthalmitis after intravitreal injection of bevacizumab, including visual acuity outcomes, microbiological testing, and compound pharmacy investigations by the Food and Drug Administration (FDA).
  
  
  METHODS
  Retrospective consecutive case series.
  
  
  METHODS
  Twelve eyes of 12 patients who developed endophthalmitis after receiving intravitreal bevacizumab prepared by a single compounding pharmacy.
  
  
  METHODS
  Medical records of patients were reviewed; phenotypic and DNA analyses were performed on microbes cultured from patients and from unused syringes. An inspection report by the FDA based on site visits to the pharmacy that prepared the bevacizumab syringes was summarized.
  
  
  METHODS
  Visual acuity, interventions received, time to intervention, microbiological consistency, and FDA inspection findings.
  
  
  RESULTS
  Between July 5 and 8, 2011, 12 patients developed endophthalmitis after intravitreal bevacizumab from syringes prepared by a single compounding pharmacy. All patients received initial vitreous tap and injection, and 8 patients (67%) subsequently underwent pars plana vitrectomy (PPV). After 12 months follow-up, outcomes have been poor. Seven patients (58%) required evisceration or enucleation, and only 1 patient regained pre-injection visual acuity. Molecular testing using real-time polymerase chain reaction, partial sequencing of the groEL gene, and multilocus sequencing of 7 housekeeping genes confirmed the presence of a common strain of Streptococcus mitis/oralis in vitreous specimens and 7 unused syringes prepared by the compounding pharmacy at the same time. An FDA investigation of the compounding pharmacy noted deviations from standard sterile technique, inconsistent documentation, and inadequate testing of equipment required for safe preparation of medications.
  
  
  CONCLUSIONS
  In this outbreak of endophthalmitis, outcomes have been generally poor, and PPV did not improve visual results at 1-year follow-up. Molecular testing confirmed a common strain of S. mitis/oralis. Contamination seems to have occurred at the compounding pharmacy, where numerous problems in sterile technique were noted by public health investigators.
authors: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. rgoldberg.eyemd@gmail.com
authors: Roger A
authors: RA
authors: Goldberg
authors: Harry W
authors: HW
authors: Flynn
authors: Darlene
authors: D
authors: Miller
authors: Serafin
authors: S
authors: Gonzalez
authors: Ryan F
authors: RF
authors: Isom
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000068258:Bevacizumab; D018834:Chaperonin 60 / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis; D004196:Disease Outbreaks; D004339:Drug Compounding; D004340:Drug Contamination; D009877:Endophthalmitis / Q000453:epidemiology* / Q000382:microbiology / Q000601:surgery; D015817:Eye Infections / Q000453:epidemiology* / Q000382:microbiology / Q000601:surgery; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D013290:Streptococcal Infections / Q000453:epidemiology* / Q000382:microbiology / Q000601:surgery; D034361:Streptococcus mitis / Q000235:genetics / Q000302:isolation & purification; D019533:Streptococcus oralis / Q000235:genetics / Q000302:isolation & purification; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D014822:Vitreous Body / Q000382:microbiology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018834:Chaperonin 60; D004269:DNA, Bacterial; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab