Update 2/3/2023 9:05am: This story has been updated to include the recall information.

An extensively drug-resistant bacterial strain is spreading in the US for the first time and causing an alarming outbreak linked to artificial tears eye drops, according to an alert released Wednesday evening from the Centers for Disease Control and Prevention. So far, the germ has caused various infections in 55 people in 12 states, killing one and leaving others hospitalized and with permanent vision loss.

Infected patients reported using more than 10 brands of artificial tears collectively, with some patients using multiple brands. But the most common brand used among the patients was EzriCare Artificial Tears, a preservative-free product sold by Walmart, Amazon, and other retailers.

On Thursday, after this story originally published, the Food and Drug Administration posted notice of a recall of EzriCare Artificial Tears and Delsam Pharma's Artificial Tears. The FDA  the CDC recommends clinicians and patients stop buying and using the two products. In a separate notice, the FDA further added that the products' manufacturer, Global Pharma Healthcare Private Limited, was in violation of good manufacturing practices, including lack of appropriate microbial testing, formulating its product without an adequate preservative, and lack of proper controls concerning tamper-evident packaging.

Formidable foe

The culprit behind the outbreak is a strain of Pseudomonas aeruginosa, an extremely versatile, innately drug-resistant bacterium that lurks in the environment, particularly freshwater. It is known to cause various skin, wound, burn, lung, and systemic infections. It most often strikes people in immune-compromised states, such as those with cystic fibrosis, and has a reputation for sparking outbreaks in health care settings, particularly among people with indwelling devices, like catheters and breathing tubes. In hospital settings, it lurks in sinks, icemakers, device washers, respiratory therapy equipment, and on soap bars.

In the current outbreak, 35 of the 55 infected patients were linked to four clusters of cases in health care facilities. Among those four health care-associated clusters, the EzriCare Artificial Tears product was the only common product among the facilities. CDC investigators also found the outbreak P. aeruginosa strain in opened containers of EzriCare Artificial Tears bottles, which were manufactured in different lots and collected from patients in two different states.

The outbreak strain is a rare, extensively drug-resistant strain with a mouthful of a name: Verona Integron-mediated Metallo-β-lactamase (VIM) and Guiana-Extended Spectrum-β-Lactamase (GES)-producing carbapenem-resistant P. aeruginosa—or VIM-GES-CRPA for short.

While multi-drug resistant P. aeruginosa strains have long posed a threat in the US and elsewhere, this is the first time VIM-GES-CRPA has been found spreading in the US. The strain is resistant to various antibiotic weapons, including: cefepime, ceftazidime, piperacillin-tazobactam, aztreonam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, fluoroquinolones, polymyxins, amikacin, gentamicin, and tobramycin, the CDC reported.

So far, antibiotic susceptibility testing on three outbreak isolates suggests that the VIM-GES-CRPA strain is still susceptible to cefiderocol, a newer antibiotic that received FDA approval in 2019 to treat multidrug-resistant urinary tract infections.

In the current outbreak, which began in May 2022, investigators have isolated the outbreak strain from 13 sputum or bronchial washes, 11 cornea swabs, seven urine samples, two blood samples, 25 rectal swabs, and four other nonsterile sources. The patients presented in inpatient and outpatient settings with a range of infections. Those include eye infections—infection of the cornea (keratitis) and infection of tissue or fluids inside the eyeball (endophthalmitis)—to respiratory infections, urinary tract infections, and sepsis. The patient who died had a systemic infection.

The cases so far occurred in 12 states: California, Colorado, Connecticut, Florida, New Jersey, New Mexico, New York, Nevada, Texas, Utah, Washington, and Wisconsin.

Response

In a statement on February 1, EzriCare, LLC said that it is cooperating with the CDC and FDA on the investigation. "As of today, we are not aware of any testing that definitively links the Pseudomonas aeruginosa outbreak to EzriCare Artificial Tears," the company said. "Nonetheless, we immediately took action to stop any further distribution or sale of EzriCare Artificial Tears. To the greatest extent possible, we have been contacting customers to advise them against continued use of the product."

EzriCare noted that it only has limited involvement with the artificial tears product—which is also marketed under other brands, the company noted, without identifying any other brands. "EzriCare, LLC's only role in introducing the product to the market was to design an exterior label and to market it to our customers," the company said. The eye drops are manufactured in India by Global Pharma Healthcare PVT Limited and imported into the United States by Aru Pharma Inc.

Global Pharma Healthcare posted a press release on its website dated February 1 saying that it is voluntarily recalling its artificial tears products.