Following the publication of a study by the Comparison of Age-Related Macular Degeneration Treatment Trials (CATT) research group (see link to NeLM report) in the New England Journal of Medicine (May 19) supporting off-label use of bevacizumab for neovascular age-related macular degeneration, a letter from the Tennessee Department of Health has been published in the journal warning of the contamination risks when compounding and dispensing bevacizumab for intravitreal use.

The authors were aware of three recent clusters of endophthalmitis secondary to alpha-haemolytic streptococcus, after intravitreal injections of bevacizumab in 9 patients, 4 (44%) of whom lost eyesight; one also had meningitis and encephalitis, although no confirmation has been received that the latter infections were caused by the same strain of alpha-haemolytic streptococcus. Two completed investigations have implicated the same compounding pharmacy in which non-compliance with face-mask usage was observed. The rules of the Tennessee Board of Pharmacy require the wearing of a mask only if no laminar-flow hood is used or if the pharmacist or technician has a respiratory condition that may result in contamination of sterile products. The pharmacist at the implicated pharmacy was observed to compound bevacizumab under a laminar-flow cabinet with no vertical barrier; the pharmacist wore no mask and spoke during the procedure. It is postulated that this resulted in contamination by oral flora (alpha-haemolytic streptococcus) of the bevacizumab.

The authors stress that “because endophthalmitis can have severe consequences, it should be considered a ‘never event’. It is also a sentinel event to identify breaches in infection control during compounding and injection procedures, because small inocula may cause devastating infections in immune-protected sites (e.g., vitreous fluid).” They acknowledge that bevacizumab provides a more economical alternative to ranibizumab to prevent blindness; but it is critical to ensure the safe use of this drug.