A new strain of “superbug” appeared in the U.S. in the past year and caused people across 16 states to begin falling ill with eye, respiratory and urinary tract infections that didn’t respond to antibiotics. As of March 14, 68 cases have been identified by the Centers for Disease Control and Prevention. Three of the infected people died, eight lost their vision, and four had to have an eye surgically removed.
Eventually a common cause became clear: bacterial contamination in bottles of “artificial tears” sold under the brand names EzriCare and Delsam Pharma and imported from a factory in India that belongs to the company Global Pharma Healthcare. Some containers of these eyedrops harbored an extremely drug-resistant strain of the bacterium Pseudomonas aeruginosa, which survived exposure to most of the medications normally used to treat it.
But 19 of the people who were infected did not report using the drops at all, according to a spokesperson for the CDC’s Antimicrobial Resistance Team. Nine of these people were identified in health care settings that had clusters of cases, including a long-term care facility in Connecticut. This raised the possibility that the bacteria had been passed from person to person through direct contact or via health care personnel or contaminated equipment. And several of the infected individuals showed no symptoms.
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Person-to-person spread of P. aeruginosa would not be surprising, especially in a health care setting, infectious disease experts say. P. aeruginosa is one of many drug-resistant pathogens that thrive in environments such as hospitals, clinics and long-term care facilities. It can cling to medical equipment and infect people with a compromised immune system. Other strains of drug-resistant P. aeruginosa caused an estimated 28,800 infections and 2,500 deaths in the U.S. in 2020, according to the CDC’s most recent data. The agency classifies the bacterium as a “serious” antibiotic-resistant threat—its second most dangerous category—alongside drug-resistant tuberculosis and methicillin-resistant Staphylococcus aureus (MRSA).
“Pseudomonas is just one of those bugs that is a survivor,” says Benjamin Chan, a Yale University evolutionary biologist who has helped treat patients with resistant P. aeruginosa infections. The new strain, never seen before in the U.S., can survive exposure to at least 12 different kinds of antibiotics—including carbapenems, key drugs given as a last resort. Fortunately, however, the new strain does appear to be susceptible to at least one other last-resort antibiotic.
P. aeruginosa “lives everywhere in the environment” and is often found in and on our body, Chan says. It is an opportunistic pathogen, meaning that it infects people with a compromised immune system. This type of bacteria also loves moist environments and can survive exposure to many disinfectants, allowing it to cling to medical supplies and sink drains. These factors have allowed P. aeruginosa to gain a foothold in health care settings, where it can then spread between patients.
“It’s definitely one of the more challenging infections to treat, regardless of its antibiotic susceptibility,” says Shiv Gandhi, an infectious disease specialist at the Yale School of Medicine. Unfortunately, he says, it is also often resistant to multiple antibiotics, making it “one of the most feared” drug-resistant organisms.
Health care settings put P. aeruginosa under extreme pressure to develop resistance. Compared with other species of bacteria, it is particularly good at evolving new cellular tactics to evade antibiotics.
“Pseudomonas has a lot of tricks up its sleeve,” Gandhi says. And one trick in particular protects it from a large swath of antibiotics: it creates enzymes called VIMs that break down nearly all beta-lactam antibiotics—a large class of medications that are “often the backbone of treating all these infections,” says Gregory Madden, an infectious disease researcher and clinician at the University of Virginia School of Medicine. VIMs are “the worst to deal with because they chew up pretty much any beta-lactam you can throw at them, including our big guns like carbapenems.” The enzymes can also break down several of the newest beta-lactam drugs. “This is where it starts to feel like the preantibiotic era, when you have no good antibiotic options to treat these infections,” he says.
Fortunately, lab tests of five samples of the new strain showed that the bacteria appear to be susceptible to one new-generation beta-lactam called cefiderocol. This is “somewhat reassuring,” although it doesn’t guarantee that every infection would respond to the medication, Madden says. According to a recent case study of a 72-year-old woman who lost almost all sight in her left eye after using the EzriCare drops, cefiderocol was used to successfully treat the woman's P. aeruginosa infection, but it did not restore her eyesight.
These new-generation beta-lactam antibiotics are lifesaving, but they all rely on similar mechanisms to kill bacteria. Very few new antibiotics take completely novel approaches to wiping out these microbes. Drug companies see antibiotic development as largely unprofitable because new antibiotics are usually only used for the most drug-resistant cases, Chan says. The recent P. aeruginosa outbreak highlights the importance of staying ahead of bacteria and fungi as they evolve immunity to the drugs in our arsenal, he adds.
Some scientists see promise in a treatment called bacteriophage therapy. Bacteriophages, often called phages for short, are viruses that naturally target and kill specific strains of bacteria. These tiny predators have been used to successfully treat drug resistant P. aeruginosa infections, including by Chan’s team at Yale. According to the CDC, the University of California, San Diego’s Center for Innovative Phage Applications and Therapeutics has identified phages that can act against the new strain of P. aeruginosa. But phage therapy is only available to those with life-threatening conditions in the U.S. and is typically not covered by insurance. Some phage therapy centers offer the treatment at free or reduced cost, however.
Drug-resistant infections are on the rise around the world. “Ten years ago these carbapenem-resistant organisms were pretty unusual and were mostly seen in other countries,” Madden says. “But in the past year or two, we’ve definitely seen many more of them in the United States.” This is likely because of a combination of factors and long-term trends, such as increased antibiotic use and higher levels of immunosuppression in the general population, he says.
The genes that allow bacteria to resist antibiotics can also be spread between different bacterial species, so the drug resistance that evolved in P. aeruginosa could jump to other types of bacteria, such as Escherichia coli. “You may get into situations where you’d have to go home with an [intravenous] antibiotic for just a regular urinary tract infection,” Madden says. “We’ve seen that. So this is a real problem. It’s only going to get worse.”
The worsening crisis emphasizes the importance of limiting our use of antibiotics, Gandhi says. “It’s really an argument for really judicious use of antibiotics. That’s probably the main way and the best way to prevent these infections from spreading.”
Editor’s Note (4/14/23): This article was edited after posting to correct the spelling of Shiv Gandhi’s last name.