Four deaths, fourteen people who no longer see, four eyeballs surgically removed, all for an over-the-counter eye drop sold freely, without a prescription, designed to relieve the discomfort of dry eyes. It is a story from 2023 (for which the products were withdrawn and the FDA alert was triggered in February 2023) and which has been talked about again in recent days but it is worth telling, because the mechanism that made that disaster possible is not yet resolved. The Centers for Disease Control and Prevention has precisely reconstructed the extent of the outbreak: as of May 15, 2023, 81 patients had been identified in 18 American states affected by a strain of Pseudomonas aeruginosa defined as VIM-GES-CRPA, an acronym which indicates such extensive resistance to carbapenems as to make the bacterium substantially intractable with the majority of available antibiotics. Before that outbreak, that particular strain had never been reported in the United States.
The bacterium, the product, the producer
The infections were not limited to the eyes. The CDC has detected cases affecting the respiratory tract, blood and other districts, with a significant number of patients identified through surveillance swabs in hospital departments. The common point of contact, which emerged from the epidemiological and laboratory investigation, were the artificial tears EzriCare Artificial Tears and Delsam Pharma Artificial Tears, both produced by Global Pharma Healthcare Private Limited, based in Chennai, India. The Food and Drug Administration previously issued the alert on February 2, 2023, urging consumers and healthcare professionals to immediately stop using EzriCare. The voluntary recall by Global Pharma was recommended by the FDA after finding violations of good manufacturing practices, such as lack of adequate microbiological testing, multi-dose bottles lacking sufficient preservative, and insufficient controls on tamper-evident packaging. The FDA then placed the company on an import alert, effectively blocking the products from entering the United States. The CDC found the VIM-GES-CRPA strain inside opened EzriCare bottles collected from patients with and without eye infections in two different states. Testing of unopened bottles, conducted by the FDA, found bacterial contamination.
Resistant to almost everything
On the clinical front, the CDC data on the strain’s antibiotic resistance leaves little room for optimism. The isolates tested showed no susceptibility to cefepime, ceftazidime, piperacillin-tazobactam, aztreonam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, fluoroquinolones, polymyxins, amikacin, gentamicin, and tobramycin, a list that covers much of the standard antibiotic arsenal. Only a subset of isolates showed susceptibility to cefiderocol, a latest generation antibiotic.
It is worth remembering: the relaunched news, recently relaunched online, contains data dating back to May 15, 2023, therefore the products we talked about have already been withdrawn from the market and the FDA alert has been active since February of the same year. The story does not describe an ongoing emergency, but a case study, useful for better understanding certain scenarios in which controls on the supply chain of imported over-the-counter drugs do not work and create the problems mentioned above.
