From battlefields to global health: the war-driven spread of multidrug-resistant bacteria

There is a growing body of evidence on the association between geopolitical conflicts and the emergence of antimicrobial resistance.¹ Studies conducted during the numerous armed conflicts of the 21st century have consistently documented the spread of multidrug-resistant (MDR) pathogens, resistant even to the newest antibiotics, in the affected areas, with the potential for global diffusion.¹

In a study of the ongoing conflict in Ukraine, 154 isolates were collected from patients with war injuries.² The study found elevated resistance rates for the newest antibiotics, i.e. a 49% resistance rate for cefiderocol, resistance rates higher than 80% for ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam and meropenem-vaborbactam.² Moreover, 6% of the isolates, all of which were identified as Klebsiella pneumoniae, exhibited pan-drug resistance.²

Reports from the Netherlands and Germany corroborated the concerns pertaining the global spread of these pandrug-resistant bacteria, which have emerged in the context of the Ukraine conflict.^3,4 In Germany, the prevalence of MDR K. pneumoniae among war refugees was identified as a substantial contributing factor to the increase of the incidence of New Delhi metallo-β-lactamase-producing K. pneumoniae, in comparison to the baseline incidence (p < 0.001).⁴

Nevertheless, the preponderance of data derived from patients receiving care elsewhere in Europe, subsequent to transfer to multiple healthcare facilities. There is a paucity of early sampling data from military hospitals in the close proximity to the point-of-injury. The lack of reliable surveillance data in the context of combat zones, along with the inherent challenges of conducting research in such environments, significantly complicates the understanding of the development of MDR infections.

In this issue of The Lancet Regional Health-Europe, Pallet et al. evaluated the phenotypic and molecular characteristics of Gram-negative bacteria isolated from conflict-wounded injuries during the ongoing war in Ukraine.⁵ A total of 100 Gram-negative isolates were collected. Of these, 69% were identified as Enterobacterales, mainly K. pneumoniae and E. coli. The remaining isolates comprised 18% A. baumannii and 13% P. aeruginosa.⁵

Alarmingly, meropenem susceptibility was reported at 14%, 0% and 8.3% among Enterobacterales, A. baumannii and P. aeruginosa, respectively.⁵ When tested for ceftazidime-avibactam, more than 60% of the Enterobacteriaceae isolates and more than 90% of the P. aeruginosa strains exhibited multi-drug resistance.⁵

Notably, the study by Pallet et al. made a comparison between phenotypic and molecular resistance for Gram-negative isolates from combat-wounded patients during the first seven days after injury and later in the treatment pathway. Of the isolates analysed, 37% were from primary infections within seven days of injury, while 63% were from later stages of patient care.⁵ It was confirmed that multi-drug resistance was present even at in the early post-injury phase, with high prevalence of New Delhi metallo-β-lactamase and OXA-48-like carbapenemases.⁵

The study also identified alternative antibiotic resistance mechanisms, including the unusual finding of New Delhi metallo-β-lactamase and KPC-producing P. aeruginosa and A. baumannii.⁵ This highlights the need for further studies on the antibiotic resistance mechanisms in Ukraine. The adoption of whole genome sequencing has the potential to yield additional insights.

The early emergence of MDR and pandrug-resistant infections in the aftermath of conflict-related injuries is a significant concern, underscoring the imperative for more consistent surveillance to inform treatment strategies and improve clinical outcomes.

A number of factors may be responsible for the development of antimicrobial resistance in war areas. In the context of conflict zones, the damage to laboratory facilities hinders microbial testing and appropriate antibiotic use.¹ Traumatic injuries need surgical intervention, which is carried out in facilities that are often lacking standard infection prevention and control measures. This increases the risk of wound contamination and the development of resistance.⁶ The use of broad-spectrum antibiotics to manage such infections can further select for resistant bacteria.⁷

Previous evidence suggests that nosocomial transmission within military healthcare facilities plays a key role.⁸ Of importance, adherence to established guidelines and the optimisation of antibiotic stewardship measures have the potential to curtail the prevalence of MDR infections among military personnel.⁹ Active surveillance and infection prevention and control measures demonstrated to minimise nosocomial transmission in military hospitals.¹⁰ It is imperative that educational initiatives targeting healthcare providers in military hospitals focus on proper antibiotic use.

To consider, in situations of conflict, the supply of emergency medical care is frequently provided by a variety of organisations, including local forces, the United Nations, the World Health Organisation, allied militaries, and non-governmental organisations. Collaboration and implementation of an international strategy is crucial to optimise surveillance and infection prevention and control. These measures have the potential to reduce the risk of antibiotic resistance during armed conflicts, to limit the spread of MDR pathogens worldwide, and to safeguard the efficacy of antibiotics for future generations.

Contributors

GG and NP equally conceptualised the manuscript and prepared the original draft and writing-reviewing and editing.

Declaration of interests

In the last two years, NP received payment or honoraria for lectures and presentations and speakers bureau from Takeda, Tillots, Valneva, Shionogi, Q-linea. GG declares no conflicts of interest.