War-torn Ukraine has become a breeding ground for lethal drug-resistant bacteria
Urgent action underway to prevent dangerous microbes from spreading beyond country's borders
- 27 Nov 2024
- 12:30 PM ET
- ByRichard Stone
On the morning of 20 April 2023, shrapnel shredded the abdomen of a 32-year-old Ukrainian soldier who goes by the call sign “Black.” After he was evacuated from the front, doctors stitched up a ruptured intestine, removed part of his colon, and plied him with antibiotics. But his condition remained “extremely serious,” recalls Viktor Strokous, a surgeon at Kyiv City Clinical Hospital No. 6.
Black had sky-high levels of white blood cells and other signs of sepsis, an often life-threatening infection. Tests indicated the presence of extremely drug-resistant (XDR) bacteria that proved impervious to every antibiotic doctors tried. In a last-ditch measure, they gave Black a drug combo suggested by a visiting microbiologist—and then waited anxiously to see whether it worked.
Now deep into its third year, Russia’s full-scale invasion of Ukraine has become a breeding ground for bacteria that can withstand the world’s most potent antibiotics. “It’s eye-opening just how incredibly resistant some of the bacteria coming out of Ukraine are. I haven’t seen anything like it,” says Jason Bennett, director of the Multidrug-Resistant Organism Repository and Surveillance Network at the Walter Reed Army Institute of Research (WRAIR).
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Ringing alarm bells the loudest is Klebsiella pneumoniae, a pathogen that globally causes one in five deaths attributable to antimicrobial resistance (AMR). Disease detectives have cultured hypervirulent Klebsiella from Ukrainian casualties, including strains described in a paper in the December issue of the Journal of Infection that are pandrug resistant—in other words, no single antibiotic can vanquish them. “That really makes Klebsiella a red flag,” says Sarah Legare, a public health specialist based in Kyiv for ICAP, Columbia University’s global health center.
To help Ukraine fight the resistant microbes, and prevent them from spilling over its borders, European and U.S. health agencies are rushing in diagnostic equipment and training hospital staff in infection prevention. The urgency derives from the lethal threat posed by AMR—a bigger killer than HIV or malaria. In 2021, AMR was the direct cause of an estimated 1.14 million deaths worldwide and a factor in an additional 4.71 million deaths, according to a 28 September report in The Lancet compiled by the Global Burden of Disease study. By 2050, the article forecasts, AMR could contribute to 10 million deaths a year. Misuse of antibiotics is a key driver of resistance, imperiling “many of the gains of modern medicine,” the World Health Organization (WHO) recently warned.
For decades, Ukraine has been known for indiscriminate antibiotic use—and then came war. Conflict zones are notorious cradles of AMR. Bullets and shrapnel embed pathogens deep in the body, “where they find the ideal conditions to thrive,” says Scott Pallett, a physician and microbiologist at the Royal Centre for Defence Medicine. If an injured soldier can’t be evacuated quickly, medics are “more likely to give broad-spectrum antibiotics” to prevent infection, he says. Pallett says such prophylactic use of the drugs, though unavoidable, can “add fuel to the fire” by promoting the evolution and spread of genes for drug resistance.
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In the killing fields of Iraq and Afghanistan in the early 2000s, the signature drug-resistant pathogen to emerge was the bacterium Acinetobacter baumannii. But although alarming, these “Iraqibacter” still succumbed to broad-spectrum antibiotics called carbapenems. Since then, however, carbapenem resistance has been gaining momentum globally. “The nastiest resistance gene floating around right now” codes for an enzyme called New Delhi metallo-beta-lactamase 1 (NDM-1), which defangs carbapenems, says WRAIR microbiologist Patrick McGann. “Pick up that one gene, and you’ve got resistance to the entire class of antibiotics.”
In Ukraine, the NDM-1 resistance gene has shown up in Klebsiella, a rod-shaped bacterium that has emerged as a singular villain. One characteristic that makes it so hardy is that compared with other bacteria, Klebsiella produces an “extraordinary” amount of mucus, says Kristian Riesbeck, a clinical microbiologist at Lund University. Thus it’s adept at forming biofilms, in which drug-resistant bacteria on the surface shield vulnerable populations deeper in the wound. According to McGann, some 80% of Klebsiella strains sequenced so far in Ukraine carry NDM-1—a rate 10 times higher than in the rest of Europe. One reason for the gene’s rapid spread: Klebsiella is adept at grabbing plasmids—extrachromosomal DNA–containing resistance genes directly from other bacteria.
Often, the metabolic cost of firing up all this extra genetic machinery makes a pathogen less virulent. Not so for Klebsiella, says Riesbeck, whose team describes in the Journal of Infection “alarmingly” hypervirulent XDR and pandrug-resistant Klebsiella strains isolated from wounded Ukrainian soldiers and civilians.
AMR in Ukraine has deep roots. As in other former Soviet countries, broad-spectrum antibiotics are sold over the counter, leading to misuse. And Ukrainian clinicians often prescribe small doses of antimicrobials over weeks or months, a “senseless” approach that fosters resistance by stressing bacteria without killing them, says microbiologist Olena Moshynets of the Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine.
Ukraine’s AMR rates began to nudge up in 2014, after fighting broke out between Ukrainian troops and Russia-backed separatists in the Donbas region. One 2020 study estimated that nearly 20% of hospital infections in Ukraine involved multidrug-resistant (MDR) bacteria–with Klebsiella the most pervasive. In 2021, Ukraine took steps to curb AMR, including regulating antibiotic sales, but those measures faltered after Russian troops invaded in February 2022.
As casualties mounted, “front-line hospitals and triage clinics were throwing whatever they could at the injured soldiers to keep them alive,” says Ezra Barzilay, a physician who heads the Kyiv office of the U.S. Centers for Disease Control and Prevention (CDC). “Antibiotic resistance was probably the last thing on their mind.” Not so at CDC and its European counterpart, which in March 2022 advised hospitals across the continent to isolate and test Ukrainian patients for resistant pathogens. The surveillance has revealed XDR cases from Ukraine in several European countries and as far away as Japan.
In Ukraine, hospitals began to encounter untreatable infections. WRAIR helped investigate the case of a Ukrainian soldier who had been severely burned and succumbed to sepsis despite multiple antibiotics. Doctors found six XDR strains in his blood and tissues. Sequencing the pathogens, McGann’s team identified a pandrug-resistant Klebsiella equipped with NDM-1 and 23 other resistance genes, they reported in August 2023 in Emerging Infectious Diseases. (A Danish team later documented a Ukrainian soldier carrying nine XDR strains.)
Researchers in Ukraine still “lack a comprehensive view of which resistance genes are out there and how the war is influencing gene patterns,” says Moshynets, who with support from Horizon Europe’s SURE-AMR program established an AMR research hub in Kyiv last month.
Then there is what Barzilay calls “the million-dollar question”: precisely where Ukrainian patients are becoming infected with MDR strains. Clarity “would really help us focus our interventions,” he says. Early studies point to regional hospitals, which are flooded with both war casualties and civilian injuries and have limited resources.
“You have hundreds of patients coming in every day,” spilling into the hallways and basements, says Dmytro Stepanskyi, a physician and microbiologist at Dnipro State Medical University. Power outages are common, and many hospitals run short of nursing staff or consumables such as water and alcohol for sterilization. In the United States, patients battling resistant infections usually get their own room and a dedicated care team, Legare says, but that’s impossible in Ukraine. In a bid to improve care, WHO, CDC, and other groups have donated automated blood culture analyzers and other tools for rapid microbial identification.
Basic researchers are also helping save lives. When Black was in dire straits at the hospital in Kyiv, it was Moshynets, who was visiting another patient, who deduced that bacteria had formed biofilms in Black’s wounds. She urged Black’s doctors to try azithromycin and meropenem, antibiotics that in tandem disrupt biofilms and enhance sensitivity to meropenem, a potent carbapenem. “Most of my colleagues did not quite believe her,” Strokous says. “But I decided to take a chance.”
The one-two punch worked, Strokous, Moshynets, and their colleagues reported in September 2023 in Frontiers in Medicine. Black was soon joking with his caregivers and was released 6 weeks later. “One patient, one treatment story is not enough” to justify broad adoption of this approach, Moshynets says. But according to Strokous, his hospital has used the combination therapy to cure more than 50 infected soldiers so far.
Despite such glimmers of hope, many public health experts fear that the war in Ukraine is adding ominous complications to the global fight against resistant microbes—a battle the world may be losing. “The level of drug resistance we are seeing in Ukraine heralds the peril of a postantibiotic era,” Pallett warns. Without a concerted effort against AMR, he says, “In 10 or 20 years, we may not have any antibiotics for many kinds of infections. And that keeps me up at night.”
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