Below: lung cavities, caused by XDR Tuberculosis
Unfortunately, various Antimicrobial-Resistant infections are widespread and rising in wartime Ukraine. This is just one facet of a worldwide challenge; WHO recently predicted that AMR infections could surpass cancer as the leading cause of death worldwide by 2050.
Bacterial resistance is predominantly caused by the misuse or overuse of antibiotics. Broad-spectrum antibiotics have long been sold over-the-counter in many former USSR countries, including Ukraine. Patients commonly self-prescribe a round of antibiotics for inappropriate illnesses, such as viral colds. Further, patients may take only a partial course of antibiotics, or local doctors may prescribe prolonged low-dose courses of antibiotics, at below therapeutic dose levels. This stresses bacteria without killing them, and fosters development of AMR bacteria. One large 2020 study found that AMR was present in 25% of hospital infections in Ukraine. Microbes may be Antimicrobial-Resistant (AMR), Multi-Drug Resistant (MDR) or Extensively-Drug-Resistant (XDR).
Antibiotic overuse is not unique to Ukraine. In the US, for example, the CDC estimates that 5 out of 6 Americans take a course of antibiotics each year, and 1 out of 3 of these treatments are unnecessary. The 2022 Global Antimicrobial Resistance and Use Surveillance System (GLASS) report highlights alarming resistance rates among prevalent bacterial pathogens. Median reported rates in 76 countries of 42% for third-generation cephalosporin-resistant E. coli and 35% for methicillin-resistant Staphylococcus aureus are a major concern. For urinary tract infections caused by E. coli, 1 in 5 cases exhibited reduced susceptibility to standard antibiotics like ampicillin, co-trimoxazole, and fluoroquinolones in 2020. This is making it harder to effectively treat common infections. Klebsiella pneumoniae, a common intestinal bacterium, also showed elevated resistance levels against critical antibiotics. Increased levels of resistance potentially lead to heightened utilization of last-resort drugs like carbapenems, for which resistance is in turn being observed across multiple regions. As the effectiveness of these last-resort drugs is compromised, the risks increase of infections that cannot be treated. Projections by the Organization for Economic Cooperation and Development (OECD) indicate an anticipated twofold surge in resistance to last-resort antibiotics by 2035, compared to 2005 levels, underscoring the urgent need for robust antimicrobial stewardship practices and enhanced surveillance coverage worldwide.
Wartime conditions facilitate the spread of AMR infections in multiple ways. Various strains of AMR bacteria may be acquired in the community, via contaminated food or physical contact with human or animal AMR carriers. Patients may harbor AMR bacteria asymptomatically in the digestive tract or in skin before injury, which is then carried into the wound during the injury event. Infection may also occur during injury, or post-injury, by bacteria in the environment, or from neighboring injured personnel. Bullets and shrapnel wounds allow contaminants deep into the body. Evacuation from the drone-infested frontlines may be impossible to do safely for multiple days. During this time, infection sets in.
When patient transport and treatment finally occur, staffing and equipment shortages may prevent adequate infection control. For instance, ambulances or ad-hoc casevac vehicles may not have access to equipment needed to fully decon contaminated surfaces, or replace bloody stretchers, etc. If there is only time to address immediate life threats, multi-trauma patients may go through several stages of evacuation with uncovered open wounds. Nurses may be caring for 15-20 patients simultaneously, and lack time or supplies to ensure clean gloves, beds, and equipment are used for every patient contact. Hospitals are overcrowded; for example, patient loads at Dnipro’s Mechnikov Hospital have increased 10-fold during the war, according to Chief Surgeon Sergiy Kosulnikov. Kosulnikov estimates that 50% of his patients developed AMR before ever starting treatment. “Has he been in hospital before? Somewhere else?”, he ponders. The origins of individual AMR infections in the Ukraine war is a key question for public health experts.
Multi-stage patient care means that patients pass through multiple facilities before discharge, with potential to acquire and spread different strains of AMR bacteria at each facility. Overcrowded facilities cannot afford to isolate AMR patients. Severely injured combat trauma patients are generally immediately started on broad-spectrum antibiotics, because care cannot be delayed several days pending results of drug-susceptibility cultures. While this is in patients’ best interests, it creates opportunities for bacteria to evolve resistance to advanced antibiotics.
Anecdotal accounts and some science are beginning to emerge on rates of wartime AMR in Ukraine. At the Feofaniya Hospital in Kyiv, for example, more than 80% of recently admitted patients had infections caused by AMR microbes, according to the hospital’s deputy chief physician. “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). A 2023 study by Ukrainian MOH and the US CDC tested 353 Ukrainian patients with hospital-acquired infections in late 2022. They found that 60% were fighting infection resistant to carbapenem antibiotics, which are considered the last resort in treating infections. A German report found a rapid rise in. AMR infections treated in Germany in late 2022, following the influx of refugees and wounded patients from Ukraine. IN 2023, a Ukrainian burn patient was treated at the US military hospital in Germany. Cultures revealed the presence of six different XDR bacterial strains, which were resistant to nearly all known antibiotics.
Ukraine is not the first war to foster AMR. Acinetobacter baumannii, or “Iraqibacter”, evolved during the Iraq war, and went on to cause 19% of European ventilator-associated pneumonia cases by 2009.
If the Ukraine war has a “signature bacteria”, it is probably Klebsiella pneumoniae. This organism is already responsible for 20% of AMR deaths worldwide. A unique feature of Klebsiella is the copious mucous it produces, which allows AMR Klebsiella colonies on the surface of the wound to act as a biofilm, shielding susceptible bacteria deeper in the wound. Cultures from Ukrainian casualties have contained hyper-virulent, pan-drug resistant strains of K. pneumoniae (i.e. only treatable with a sophisticated multi-drug cocktail).
AMR prevention: Local measures. Good infection control measures are crucial to preventing spread of AMR in hospitals and on ambulances.
Gloves should be changed between patients
Provide handwashing facilities and encourage frequent use by providers and patients
All commonly touched ambulance surfaces should be cleaned with hospital-grade disinfectant after every transport. Patient treatment areas in-facility should be cleaned thoroughly between patients. Ensure the cleaning agent has enough contact time (see bottle, or ~1-2min on the surface before drying occurs).
Fully decontaminate or replace all instruments and patient care equipment between patients (including trauma shears, BVMs, etc)
Keep a fresh, clean sheet or mylar foil blanket on stretchers and hospital beds
Irrigate away gross wound contamination with sterile fluids as early as possible in stable patients (but do not risk causing hypothermia to do so)
If time allows, cut away patient clothing to remove as many gross contamination sources as possible, before pt transfer from ambo stretcher onto a facility bed
Cover open wounds, when possible, with CLEAN dressings. Be careful not to cross-contaminate multi-packs of dressings and other materials.
Avoid unnecessary dressing changes during interfacility transports
Nationally, Ukraine is making efforts to reduce AMR spread. In 2022, Ukraine ceased over-the-counter sales of antibiotics. A prescription is now required.
On an international level, the US CDC and ICAP are working to strengthen AMR surveillance, prevention, and treatment in three Ukrainian pilot hospitals and labs. These are large regional facilities in Vinnytsia, Ternopil, and Khmelnytskyi. The selected hospitals “are dealing with the equivalent of a mass casualty event on a weekly basis because there are so many people getting injured,” said ICAP’s regional AMR advisor. The project also supports the national reference lab at the Ukrainian Public Health Center.
By Sept 2024, Ukraine had 100 labs carrying out surveillance for AMR bacteria, as compared to just 3 in 2017. Yet, no systematic data collection for wound infections yet exists in Ukraine. The University of Colorado School of Medicine was recently awarded a $5million US DOD grant to create such infrastructure. This project is called the ARROW (Antimicrobial Resistance Research to Improve Outcomes of Traumatic Wounds) study.
BBC Newstory: Dangerous Drug-Resistant Bacteria are Spreading in Ukraine
WHO: AMR Could Surpass Cancer as the Leading Cause of Death by 2050
Science: War-torn Ukraine has become a breeding ground for lethal drug-resistant bacteria
