Plenty of medicine cabinet staples can kill you. In fact, some are quite well known for causing serious health problems. If I was told about someone dying because of a drug purchased over-the-counter at a local convenience store or pharmacy, I would put my money on acetaminophen. That particular drug, which is extremely safe when used appropriately for fever and/or pain, even in newborn infants, manages to put 2,600 people in the hospital and kill about 500 of them every year in the United States when too much is ingested. I certainly wouldn’t have thought of eye drops.
But here we are. At deadly eye drops.
In February, the FDA issued a recall of two brands (EzriCare, Delsam Pharma) of OTC artificial tear lubricant eye drops after the CDC had reported an outbreak of infections across 12 states. The outbreak had affected consumers who had used these products from May of 2022 through January 2023. The 55 reported cases known at that time involved infections of the eyes, with some resulting in permanent vision loss, as well as the respiratory and urinary tracts. One unfortunate victim had even died from a bloodstream infection (sepsis) with the bacteria that had contaminated these products.
Last week, the CDC released an updated report identifying a total of 81 cases across 18 states (CA, CO, CT, DE, FL, IL, NC, NJ, NM, NV, NY, OH, PA, SD, TX, UT, WA, WI). These cases include 18 with permanent loss of vision, 4 of which required complete surgical removal of an eye. Finally, the death toll now sits at 4 people who simply wanted relief from dry eyes.
The bacterial contaminant in question is a particular strain of Pseudomonas aeruginosa (VIM-GES-CRPA) that is extremely resistant to even very broad spectrum antibiotic treatment. Essentially, every antibiotic I’ve ever heard of is ineffective. Normally I would caution readers to take that with a bit of a grain of salt, because I am only a simple country pediatric hospitalist, but this bacterial is seriously resistant.
Bacteria isolated from 5 of the patients were found to be susceptible only to cefiderocol, a drug that was approved in the United States in 2019 as a last ditch treatment for certain highly resistant bacterial strains, Pseudomonas aeruginosa being one of them. Sadly there is already significant resistance being reported to this antibiotic around the world. One other antibiotic, a combination of aztreonam and avibactam, was found to inhibit growth on an agar plate at certain concentrations in some of the isolates, which does not always equate to being a successful treatment approach because human and bacterial physiology is highly complex and at times unpredictable.
These cases represent the first time that this particular combination of antibiotic resistance genes has been found in combination in the United States. Both genes result in the production of enzymes, in this case a Verona integron-encoded metallo-β-lactamase (VIM) and Guiana-Extended Spectrum-β-Lactamase (GES), that break down antibiotics before they can cause any damage to the bacteria. And they are easily spread to non-resistant strains via plasmid transfer, so the risk of them taking hold here should be taken very seriously.
You know it’s bad when the CDC is talking about bacteriophages as a potential treatment. These are viruses that that target and kill specific bacterial species, or even a unique strain within a species, which can be a good or bad thing. Certain bacteria only become pathogenic, with release of harmful toxins, after being infected by a phage. Phage-encoded toxin production is largely behind diseases such as cholera, diphtheria, and botulism, for example. Phages can also serve as vectors for transferring antibiotic resistance genes between bacteria.
Phages have been used to treat bacterial infections in the past, typically only when approved for compassionate use in extreme circumstances. The process of finding the right phage can be lengthy and we have not worked out how to consistently get phages where they are needed in the body. And that is just the tip of the iceberg when it comes to the challenges inherent in this type of treatment, which is still in its infancy despite having been discovered a century ago.
The CDC has already announced that the University of California at San Diego’s Center for Innovative Phage Applications and Therapeutics and the Yale Center for Phage Biology and Therapy have completed the first step and identified a phage active against the bacteria implicated in the current outbreak. That is good news, but hopefully it won’t come to that. The best means of preventing additional infections and spread of the genes associated with such extreme antibiotic resistance is to avoid using these products.