How War-Torn Ukraine Became a Breeding Ground for Super-Resistant Bacteria

Deadly Klebsiella

The pathogen Klebsiella pneumoniae is globally responsible for one in every five deaths caused by antimicrobial resistance (AMR). Analysis of samples from Ukrainian war casualties (injured soldiers and civilians treated for burn and shrapnel wound infections) discovered several strains of K. pneumoniae that are pan-resistant. This means that infections by these pathogens are not treatable with any antibiotic monotherapy. The analyzed bacteria contained several genes that confer resistance to carbapenem, cephalosporin, and colistin antibiotics.

Carbapenem resistance is particularly caused by the presence of New Delhi metallo-beta-lactamase 1 (NDM-1). The NDM-1 gene was detected in approximately 80% of the Ukrainian K. pneumoniae strains sequenced so far, which is about 10 times more frequent than in the rest of Europe.

The energy demands of maintaining resistance genes often make bacteria less virulent. However, for Klebsiella, considering the hypervirulent strains described above, this does not seem to apply, as resistance to colistin was additionally associated with higher virulence.

Another problem is Klebsiella's ability to produce a large amount of mucus, which enables it to efficiently form biofilms. Under the surface protected by a resistant biofilm, even bacteria sensitive to antibiotic therapy survive. This provides another opportunity for the exchange of plasmids carrying resistance genes.

Is it "just" the war to blame?

Ukraine has long been known for somewhat reckless use of antimicrobial therapy. Broad-spectrum antibiotics were available without prescription after the fall of the Soviet Union, and some Ukrainian doctors were accustomed to prescribing long-term treatments with low doses of antibiotics. This outdated approach to the spread of resistance directly contributes by exposing bacteria to stress without killing them.

The share of AMR infections in Ukraine began to slowly rise after the first conflicts in Donbas in 2014. Estimates from 2020 indicated that nearly one-fifth of hospital infections in Ukraine were caused by multidrug-resistant bacteria, with K. pneumoniae at the top of the list. In 2021, Ukraine set rules for combating AMR, including regulating the dispensing of antibiotics. However, these new measures were quickly disrupted by the Russian invasion in February 2022.

Incubator of Resistance

With the rising number of casualties, wartime doctors naturally tried to save injured soldiers and did everything to keep them alive. Antibiotic resistance was understandably not at the top of their priority list.

The U.S. Centers for Disease Control and Prevention (CDC) and its European counterpart, however, recommended in March 2022 that hospitals across the continent isolate and test treated Ukrainian patients for the presence of resistant pathogens. Monitoring then revealed extremely resistant strains originating from Ukraine in several European countries, and even as far as Japan.

Meanwhile, hospitals in Ukraine have begun to struggle with untreatable infections. There was a documented case of a Ukrainian soldier who was a carrier of 9 extremely resistant genes.

War zones are an ideal incubator for the development of such bacteria. Injuries caused by bullets and shrapnel carry pathogens to poorly accessible places deep in the body, where they have ideal conditions for growth and mutual contact allowing for the exchange of plasmids. If the injured cannot be quickly evacuated and operated on, they are often preventively given broad-spectrum antibiotics. Although prophylactic administration of antimicrobial therapy is inevitable considering life-saving, it contributes to the evolution and spread of resistance genes.

A Million Dollar Question

It is still unclear exactly where infections with multidrug-resistant strains occur. Preliminary data points to regional hospitals, which are overwhelmed with victims from the front lines and injured civilians and have limited resources. Often, there is a lack of nursing staff, basic equipment, and consumables such as water and alcohol for sterilization. Isolation of patients with resistant infection is often not possible due to hospital overcrowding.

Prolonged Fight Against AMR

Many public health experts fear that the war in Ukraine significantly complicates the global fight against resistant bacteria. Microbiologist Scott Palett from the British Royal Centre for Military Medicine warns, "The level of drug resistance we are observing in Ukraine heralds the danger of a post-antibiotic era. Without concentrated efforts to combat AMR, we may have no antibiotics available for many types of infections in 10 or 20 years. And that keeps me up at night."

Editorial Team, Medscope.pro

Sources:

1. Ljungquist O., Magda M., Giske C. G. et al. Pandrug-resistant Klebsiella pneumoniae isolated from Ukrainian war victims are hypervirulent. J Infect 2024 Dec; 89 (6): 106312, doi: 10.1016/j.jinf.2024.106312.
2. Stone R. War-torn Ukraine is breeding drug-resistant bacterial strains. Science. Available at: www.science.org/content/article/war-torn-ukraine-has-become-breeding-ground-lethal-drug-resistant-bacteria