CLEVELAND — A 72-year-old Northeast Ohio woman is now the 69th patient impacted in the U.S. by the over-the-counter (OTC) artificial tears outbreak.
The unidentified woman was treated at University Hospitals Cleveland Medical Center late last year by ophthalmologist, Dr. Amy Kloosterboer and Infectious Disease specialist, Dr. Morgan Morelli.
This was weeks before anyone knew that pseudomonas aeruginosa bacteria had contaminated OTC eye drops.
The woman came into the emergency room a week after she lost vision in her left eye. At first doctors didn’t correlate her eye drops with the infection. Pseudomonas is a water-born bacteria that is not uncommon. It’s usually the cause behind swimmer’s ear infections.
Doctors thought the patient’s case was a fluke, but thought to test all of the eye medications she had been using. That’s when the lab found the bacteria in one of the bottles of eye drops she was using.
Dr. Morelli reported the findings to the Ohio Department of Health and sent the sample for additional testing. She says the CDC contacted her this week to inform her that the bacteria is the same as what is in the outbreak.
Unfortunately, the woman’s prognosis is that she likely lost her vision permanently in her left eye.
The doctors also published their findings to JAMA Ophthalmology on Wednesday.
Ohio is now the 17th state with a case of contaminated eye drops.
On Wednesday, U.S. officials reported two more deaths and additional cases of vision loss linked to eyedrops tainted with a drug-resistant bacteria.
In the latest government tally, infections from the bacteria have now caused a total of three deaths and eight cases of people losing their vision, the Centers for Disease Control and Prevention reported on Tuesday. That's up from one death and five cases of permanent vision loss reported last month.
The CDC said four people have undergone surgery to remove an eyeball due to the infections.
The outbreak is considered particularly worrisome because the bacteria driving it is resistant to standard antibiotics.
The CDC has now identified cases in 16 states, including California, New York, Illinois, Texas and Pennsylvania. Most of the cases have been linked to four regional clusters and Ezricare's drops are the only product used by patients in each of those groups.
The recalled drops were manufactured by Global Pharma Healthcare in India, where the bacteria — Pseudomonas aeruginosa — is commonly linked to outbreaks in hospitals. It can spread through contaminated hands or medical equipment.
How officials cracked case of eyedrops that blinded people
The investigation started in May in Los Angeles County, California. A patient who'd recently been to an ophthalmologist came in with a bad eye infection. A month later, local health officials got a second report. Another bad eye infection, same eye doctor.
Two more cases were reported in the county before the summer was over. The patients’ eyes were inflamed with heavy yellow pus that obscured most of the pupil. Among the four, two had complete vision loss in the affected eye.
The hospital that reported the first infection determined it was caused by a bacteria called Pseudomonas aeruginosa. The institution, which was equipped to do advanced genetic testing, quickly realized the bacteria had a rare gene that protected it from the effects of commonly used antibiotics.
It was an early break for investigators, said Kelsey OYong, of the Los Angeles County Department of Public Health.
OYong and her colleagues knew they were dealing with a scary germ, and they notified the Centers for Disease Control and Prevention.
Pseudomonas infections are not new. Drug-resistant strains of the bacteria cause more than 30,000 infections annually among hospitalized patients in the U.S. and more than 2,500 deaths, the CDC said. It can spread through contaminated hands or medical equipment, and is particularly dangerous to fragile patients who have catheters or are on breathing machines.
But the California infections were in patients' eyes, not more common spots like the blood and lungs. Also, the lab analysis determined the infections were caused by a Pseudomonas germ that could resist just about every antibiotic.
The only thing that worked was a newer antibiotic called cefiderocol, administered by IV.
Over the summer, Pseudomonas outbreaks were seen at long-term care facilities in two other states.
In Connecticut, the first case was in June. Eventually, the bacteria was found in 25 patients from five nursing homes in different parts of the state, said Christopher Boyle, a spokesperson for Connecticut’s health department.
In Davis County, Utah, north of Salt Lake City, the first of six cases was reported to the CDC in August. While the patients had the bacteria, none actually got sick, said Sarah Willardson of the Davis County Health Department.
L.A. County health investigators thought the cases there might be due to some kind of equipment contamination at the eye doctor’s office.
But that suspicion faded in early October, when genetic testing showed the clusters in California, Connecticut and Utah were all caused by the same bacteria strain — a version of the germ that hadn’t been seen anywhere before.
“That made us start thinking that this was some kind of a product,” said Maroya Walters, the CDC official supervising the investigation.
As the year went on, other reports of drug-resistant Pseudomonas came in, including a Washington man who died with a bloodstream infection.
Given the initial cluster at the California ophthalmologist’s office, investigators suspected an eye care product was the culprit, though that hypothesis was complicated by the fact that the infections at the long-term care facilities were mainly found in the lungs.
But it wasn’t impossible. Tear ducts drain into the nasal cavity, which leads to the lungs and could provide a path to deep inside the body.
In early November, investigators determined most of the infected Connecticut patients had been given artificial tears, though it wasn't clear who had been given which brand.
Then, on Nov. 9, a Florida hospital contacted the CDC to report bad eye infections connected to an outpatient clinic. A check of artificial tears brands used in Connecticut, Florida and Utah pointed to one common product: EzriCare Artificial Tears, an over-the-counter product marketed in the U.S. by New Jersey-based EzriCare LLC and made in India by Global Pharma Healthcare.
The Pseudomonas bacteria is “pretty much everywhere” in India and the drug-resistant germ is common in many hospitals, said Dr. Gagandeep Kang, who studies microbes in the Christian Medical College in the same state as Global Pharma's factory.
In January, genetic sequencing confirmed the Florida cases were caused by the same bacteria strain as the clusters in California, Connecticut and Utah. On Jan. 20, the CDC urged doctors to avoid recommending the EzriCare product.
There was no recall or widespread public notice, however. Investigators had strong circumstantial evidence pointing toward the EzriCare drops, but didn’t get more conclusive proof until more than a week later after testing found the bacteria in seven open bottles of EzriCare Artificial Tears in Connecticut and New Jersey.
In early February, CDC officials issued a public health alert and the FDA recalled the EzriCare eyedrops and Delsam Pharma’s Artificial Tears, another product made by Global Pharma. Last week, the recall was expanded to include Delsam Pharma’s Artificial Eye Ointment.
Global Pharma didn't respond to emailed requests for comment.
A month before the first recall, the FDA blocked imports of Global Pharma products.
FDA spokesperson Audra Harrison said the U.S. import ban was “unrelated to the outbreak," and was instead based on the company’s “inadequate response” to a records request and problems with its manufacturing procedures. She wouldn't say what those problems were.
The subsequent recall, she said, was recommended due to lack of microbial testing and issues with the product’s formulation and packaging.
The FDA, tasked with assuring the safety of drug products shipped to the U.S., has long struggled to inspect facilities in China and India that account for the vast majority of raw materials used in American medicines. A search of FDA’s online inspection database shows no records of agency staff visiting the plant.
Indian drug inspectors visited the plant and the country's drug controller asked Global Pharma to stop making all products related to treating eye disorders until they finish their investigation, said P.V. Vijayalakshmi, the drug controller for southern Tamil Nadu state.
Ostrosky, the University of Texas expert, called the U.S. investigation “a public health victory” saying it shows that fighting drug-resistant bacteria requires international collaboration and investment. But he also said the case is disheartening.
An infection that's usually easy to treat with common antibiotic eyedrops "has become an infection that can be deadly and has pretty much no treatment except one IV antibiotic,” he said.
Pseudomonas now joins a growing list of bugs — including bacteria that cause urinary tract infections — that are getting increasingly difficult to treat, Ostrosky added.
“It's like a wave coming for us," he said.