NEW YORK – The eyes of the patients were painfully inflamed. They could sense light but see almost nothing else. A doctor called one case the worst eye infection he had ever seen.
It was the start of a national outbreak caused by a very worrying bacterium – which some say is ushering in an era when antibiotics are no longer effective and seemingly routine infections are horribly out of control.
At last count, 58 Americans in 13 states have been infected, including at least one who died and at least five who experienced permanent vision loss. All have been linked to tainted eye drops, leading to a recall.
Experts are amazed at how disease investigators put the case together: the patients were scattered across the country. The illnesses developed over months. The infections were found in different parts of the body – in the blood of some patients, in the lungs of others.
But scientists also shudder because they have long feared that ordinary bacteria will develop in this way Antibiotics no longer work against them.
“It really shows us that it’s nothing theoretical and future-proof. It’s here,” said Dr. Luis Ostrosky, an infectious disease expert at the University of Texas Health Science Center at Houston.
This report is based on telephone and email interviews with US disease researchers, three state health officials and regulators in the US and India.
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The investigation began in May in Los Angeles County, California. A patient who recently saw an ophthalmologist came in with a bad eye infection. A month later, local health authorities received 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. Of the four, two had complete loss of vision in the affected eye.
The hospital that reported the first infection determined it was caused by a bacterium called Pseudomonas aeruginosa. The facility, equipped for advanced genetic testing, quickly realized the bacterium 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 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 bacteria cause more than 30,000 infections in US hospital patients and more than 2,500 deaths annually, according to the CDC. It can spread through contaminated hands or medical equipment, and is particularly dangerous for vulnerable patients on catheters or ventilators.
But the California infections appeared in patients’ eyes, not more common spots like blood and lungs. In addition, the laboratory analysis determined that the infections were caused by a Pseudomonas germ that could resist almost any antibiotic.
The only thing that worked was a newer antibiotic called cefiderocol given intravenously.
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Pseudomonas outbreaks were observed at long-term care facilities in two other states over the summer.
Connecticut had its first case in June. Eventually, the bacteria were found in 25 patients from five nursing homes in different parts of the state, said Christopher Boyle, a spokesman for the Connecticut Department of Health.
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 Department of Health.
LA County health investigators thought the cases could be due to some type 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 strain of bacteria — a version of the germ that hadn’t been seen anywhere before.
“That led us to believe this was some kind of product,” said Maroya Walters, the CDC officer overseeing the investigation.
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Additional reports of drug-resistant Pseudomonas came in throughout the year, including a Washington man who died of a bloodstream infection.
Given the initial cluster at the California eye doctor’s office, investigators suspected an eye care product was the culprit, although this hypothesis was complicated by the fact that the infections at the long-term care facilities were found primarily in the lungs.
But it wasn’t impossible. Tear ducts open into the nasal cavity, which leads to the lungs and could provide a route deeper into the body.
In early November, investigators found that most infected Connecticut patients had been given artificial tears, although it was not clear who had received which brand.
Then, on November 9, a Florida hospital contacted the CDC to report serious eye infections related to an ambulance. A review of artificial tear brands used in Connecticut, Florida and Utah pointed to a common product: EzriCare Artificial Tears, an over-the-counter product marketed in the US by New Jersey-based EzriCare LLC and manufactured in India by Global Pharma Healthcare becomes.
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The Pseudomonas bacterium is “pretty much everywhere” in India and the drug-resistant germ is rampant in many hospitals, said Dr. Gagandeep Kang, who studies microbes at Christian Medical College in the same state as Global Pharma’s factory.
In January, genetic sequencing confirmed that the Florida cases were caused by the same strain of bacteria as the clusters in California, Connecticut and Utah. On January 20, the CDC asked physicians not to recommend the EzriCare product.
However, there was no recall or widespread public service announcement. Investigators had strong circumstantial evidence pointing to the EzriCare drops but only received more conclusive evidence more than a week later after tests 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 EzriCare eye drops and Delsam Pharma’s artificial tears, another Global Pharma product. Last week, the recall was extended to Delsam Pharma’s artificial eye ointment.
Global Pharma did not respond to emailed requests for comment.
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A month before the first recall, the FDA blocked imports of Global Pharma products.
FDA spokeswoman Audra Harrison said the U.S. import ban had “no connection to the outbreak” and was instead based on the company’s “inadequate response” to a request for records and problems with its manufacturing processes. She didn’t want to say what those problems were.
The subsequent recall, she said, was recommended due to a lack of microbial testing and issues with the product’s formulation and packaging.
Tasked with ensuring the safety of drugs shipped to the United States, the FDA has long struggled to inspect facilities in China and India, which are responsible for the vast majority of raw materials used in American drugs. A search of the FDA’s online inspection database reveals no records of agency employees who have visited the facility.
Indian drug inspectors visited the facility and the country’s drug inspector asked Global Pharma to halt manufacturing of all products related to the treatment of eye diseases until they complete their investigation, said PV Vijayalakshmi, the drug inspector for southern Tamil Nadu state.
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Ostrosky, the University of Texas expert, called the US probe “a public health victory” and said it shows that tackling drug-resistant bacteria requires international collaboration and investment. But he also said the case was disheartening.
An infection that is usually easily treated with standard antibiotic eye drops “has become an infection that can be fatal and has almost no treatment other than an intravenous antibiotic,” he said.
Pseudomonas now joins a growing list of bacteria — including bacteria that cause urinary tract infections — that are becoming increasingly difficult to treat, Ostrosky added.
“It’s like a wave coming at us,” he said.
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AP writers Matthew Perrone in Washington and Aniruddha Ghosal in New Delhi contributed.
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