Two concurrent multistate outbreaks of fungal endophthalmitis have been linked to intraocular use of contaminated products labeled as sterile from a single compounding pharmacy, according to a Centers for Disease Control and Prevention (CDC) report published online January 15 and in the February issue of Emerging Infectious Diseases.
"Fungal endophthalmitis is a rare but serious infection," write Christina A. Mikosz, MD, MPH, from the Centers for Disease Control and Prevention in Atlanta, Georgia, and colleagues. "In March 2012, several cases of probable and laboratory-confirmed fungal endophthalmitis occurring after invasive ocular procedures were reported nationwide."
Nine cases of fungal endophthalmitis were reported among patients at the same Los Angeles County ambulatory surgical center who had undergone pars plana vitrectomies between October and December 2011. During surgery, all 9 patients had been exposed to a single lot of Brilliant Blue G dye (BBG) produced on August 23, 2011, at Franck's Compounding Lab (Franck's), a compounding pharmacy in Ocala, Florida.
A case–control study matched these 9 case-patients with 33 control participants who underwent vitrectomy at the same ambulatory surgical center. The only factor significantly associated with case status was Franck's BBG (P < .001). Microbiological testing of an unopened BBG vial from the same lot revealed it was positive for Fusarium, an environmental mold.
To identify additional cases of fungal endophthalmitis associated with invasive ocular procedures, identify the outbreak source, and prevent further exposures and illness, the CDC then launched a multistate investigation.
In total, investigators identified 47 cases in 9 states, linked to 2 Franck's products (BBG and triamcinolone acetonide for intravitreal injection). The implicated triamcinolone was contaminated with Bipolaris hawaiiensis, a rare environmental mold. Two case–control studies confirmed there were 2 separate outbreaks, both associated with Franck's, and a third case–control analysis separately examined probable cases.
"The rarity of the infections in these outbreaks provided an additional clue to clinicians that an atypical event had occurred, underscoring the crucial role of clinicians in recognizing unusual disease clusters and promptly reporting them to public health authorities for rapid epidemiologic investigation necessary to rule out widespread exposure," the authors write.
Cases Had Serious Sequelae
Exposure to either product was the only factor significantly associated with case status (P < .001). Twenty-one cases of fungal endophthalmitis were associated with BBG exposure and Fusarium mold; all had unusual vision loss, 76% had eye pain, and 19% had floaters. Despite antifungal treatment in 81%, after 6 months, 14% did not have documentation of resolved infection.
Nineteen cases were associated with Franck's triamcinolone exposure and Bipolaris mold. All but 1 had unusual vision loss, 21% had pain, and 32% had floaters. All received antifungal treatment, but documentation of resolved infection after 6 months was unavailable for 42%, and 2 patients required enucleation because of severe infection.
In response to an US Food and Drug Administration investigation that found fungal growth in Franck's clean room, where sterile compounds were produced, on May 25, Franck's suspended all sterile compounding services and recalled all sterile compounded products distributed from November 21, 2011, to May 21, 2012.
Compounding is primarily regulated at the state level. These 2 concurrent outbreaks of fungal endophthalmitis were neither the first outbreaks linked to contaminated compounded products nor the first investigation of Franck's for improper compounding practices.
"Maintenance of the safety and integrity of sterile compounded drugs in the United States demands a thorough review and improvement of compounding pharmacy regulatory practices," the study authors conclude.