An Outbreak of Fungal Endophthalmitis After Intravitreal Injection of Compounded Combined Bevacizumab and Triamcinolone

Abstract

IMPORTANCE Our experience may be useful to other practitioners using compounded intravitreal agents, those suspecting infectious outbreaks, and those managing fungal endophthalmitis. OBJECTIVE To describe a series of patients with fungal endophthalmitis following intravitreal injection of combined bevacizumab and triamcinolone acetonide prepared by the same compounding pharmacy. DESIGN AND SETTING Noncomparative case series. PARTICIPANTS Eight eyes of 8 patients who received an intravitreal injection of compounded combined bevacizumab-triamcinolone in a period of 3 weeks had subtle, nonspecific findings that were later diagnosed as fungal endophthalmitis. MAIN OUTCOME MEASURES Visual acuity, response to antimicrobial therapy, and number of vitreoretinal surgical operations after diagnosis of fungal endophthalmitis. RESULTS Eight patients developed endophthalmitis 41 to 97 days after receiving the intravitreal injection, which was prepared by the same compounding pharmacy. The injections occurred at the same location in New York. Treatment was based on clinical examination findings and knowledge of the etiology of the endophthalmitis. Eventually, all patients were treated with oral voriconazole. Five of 8 patients were initially treated with intravitreal antimicrobial agents. After 3 months of follow-up, visual acuities ranged from 20/50 to hand motions. Local, state, and federal health department officials were involved in investigating the source of the outbreak. CONCLUSIONS AND RELEVANCE In the current study, we report a fungal endophthalmitis outbreak after intravitreal injection of contaminated, compounded combined bevacizumab-triamcinolone. In this series, Bipolaris hawaiiensis was the identified causative agent. The challenge of medical diagnosis, identification of the source of the outbreak, and management experience are highlighted in our series. Our experience may be useful to other practitioners using compounded intravitreal agents, those suspecting infectious outbreaks, and those managing fungal endophthalmitis.

Clinical and Pathologic Features ofBipolarisEndophthalmitis After Intravitreal Triamcinolone

“…To our knowledge, this is the first reported ocular histology on a series of intraocular infections due to Bipolaris hawaiiensis. The clinical findings of another 9 cases of Bipolaris hawaiiensis endophthalmitis from the same pharmacy (Franck's Compounding Pharmacy, Ocala, Florida) and same lot number were recently reported by Sheyman et al 3 The same pharmacy a few months earlier had been involved in Brilliant Blue dye fungal contamination. The Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report described 33 cases of fungal endophthalmitis from 7 different states from March to April 2012.…”

“…2 Endophthalmitis from the same compounding pharmacy was recently reported but without ocular histology. 3 Very rarely, central nervous system infections have been described. 4 Immunocompromised individuals are at the highest risk for infection by Bipolaris species.…”

“…DNA sequencing of vitrectomy samples from early clinical cases by the Centers for Disease Control and Prevention documented the species to be identical to those from New York. 3 The most rapid and effective proof that fungi were present was PAS staining of cytospin specimens obtained via vitrectomy ( Table 2). The morphology of Bipolaris hawaiiensis in our cases was remarkably variable including vitreally in all 5 cases (Table 2).…”

Evaluation of Compounded Bevacizumab Prepared for Intravitreal Injection

“…Eight patients were diagnosed as having fungal endophthalmitis after receiving an intravitreal injection of combined bevacizumab-triamcinolone produced by a compounding pharmacy in New York. 16 In another incident, an injection of counterfeit bevacizumab in Shanghai, China, led to acute intraocular inflammation caused by endotoxin. 17 With the spotlight on endophthalmitis and sterile compounding practices, it was reassuring to find that in our analysis of syringes from 11 compounding pharmacies, there were no microbial contaminants noted in any of the samples when cultured by our clinical microbiology laboratory.…”

Black Molds and Melanized Yeasts Pathogenic to Humans

“…They are particularly associated with chronic pansinusitis (Toul et al 2006). Other cases include endophthalmitis and orbital cellulitis (Newell et al 2006;Sheyman et al 2013), necrotizing pneumonia and allergic bronchopulmonary mycosis (Saenz et al 2001;Chowdhary et al 2011Chowdhary et al , 2014b, peritonitis (Bava et al 2003), endarteritis (Ogden et al 1992), and encephalitis (Morton et al 1986;Pauzner et al 1997). Colonies are black, hairy, and expanding.…”