Armed conflict is a potent driver of antimicrobial resistance, and infections in combat-related injuries caused by multidrug-resistant organisms (MDROs) have become a defining problem in contemporary military trauma care. This narrative review integrates evidence from conflicts in Iraq, Afghanistan, and the ongoing war in Ukraine to characterize the evolving MDRO threat during large-scale combat operations (LSCO) and prolonged field care (PFC).
The review emphasizes the progression documented in recent conflicts from multidrug-resistant to extensively drug-resistant (XDR) and pan-drug-resistant (PDR) pathogens and examines implications for clinical management, infection prevention, diagnostics, stewardship, and logistics during LSCO and PFC.
The authors conducted a narrative literature review using MEDLINE/PubMed for English-language publications between January 2008 and April 2026. Search terms combined concepts including war, armed conflict, combat injury, Iraq, Afghanistan, Ukraine, antimicrobial resistance, and multidrug-resistant organisms. Sources eligible for inclusion were peer-reviewed original research, systematic and narrative reviews, and military clinical guidelines.
Standard consensus definitions for MDR, XDR, and PDR were applied to classify organism resistance profiles throughout the review.
Combat-related infections tend to be polymicrobial and are dominated by Gram-negative bacilli. The burden and complexity of resistant infections have escalated over successive conflicts, altering empiric therapy choices and complicating infection control.
The Trauma Infectious Disease Outcomes Study (TIDOS) quantified MDR Gram-negative infection among infected casualties from Iraq and Afghanistan, finding MDR organisms in approximately 27% of infected patients in that cohort.
Across the examined conflicts, prominent pathogens include Acinetobacter baumannii, Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales. Surveillance data, especially from Ukraine, indicate a qualitative escalation in resistance mechanisms and clinical severity.
Reports from recent surveillance document high rates of meropenem resistance: up to 72% in A. baumannii and 83%–91% in Klebsiella pneumoniae. Carbapenemase co-production—specifically NDM-1, OXA-48, and KPC-2—has been frequently observed. There are also increasing reports of resistance to last-line agents such as cefiderocol and ceftazidime-avibactam, and instances where resistance traits converge with hypervirulence in internationally distributed high-risk clones.
Data from Iraq and Afghanistan, including the TIDOS cohort, illustrate the emergence and burden of MDR Gram-negative infections among combat casualties. The reported 27% MDR infection rate in infected casualties underscores the clinical relevance of resistant pathogens in military trauma populations and the ongoing challenge for treatment and outcomes in deployed and evacuated patients.
Surveillance from the Ukraine conflict demonstrates an escalation in both the prevalence and severity of resistance. Key observations include very high meropenem resistance rates in A. baumannii and K. pneumoniae and widespread presence of multiple carbapenemase genes within isolates. These surveillance signals also report diminishing activity of agents formerly reserved for last-line therapy, raising concerns about therapeutic options for severely injured patients.
The review highlights the additional concern of international dissemination: repatriation of foreign combatants who are colonized or infected with XDR organisms represents an unprecedented vector for spreading resistant strains across borders.
Available evidence suggests that acquisition of MDROs in combat casualties is predominantly nosocomial, occurring along the medical evacuation pathway rather than at the initial point of injury. Frontline wound cultures and surveillance imply that colonization and subsequent infection are more likely related to exposures during evacuation and treatment in higher echelons of care than to the initial battlefield contamination.
This pattern shifts the focus of prevention efforts toward infection control and antimicrobial stewardship across all roles of care in the evacuation chain.
The escalating MDRO burden has direct implications for LSCO and PFC. Clinically, increased resistance reduces the effectiveness of empiric regimens and narrows therapeutic options for serious infections. Operationally, MDROs threaten force readiness by prolonging recovery and complicating casualty care in austere environments.
From a public health and international perspective, the repatriation or transfer of patients colonized with XDR organisms raises the risk of cross-border dissemination of high-risk clones carrying multiple carbapenemases and resistance to last-line agents.
The review proposes several broad mitigation priorities:
Implement standardized antimicrobial protocols across Role 1 and Role 2 levels of care to reduce inconsistent antibiotic use and inappropriate exposures that select for resistance.
Centralize oversight and coordination under the Defense Health Agency to harmonize surveillance, treatment guidelines, and resource allocation across military health facilities.
Deploy rapid diagnostic tools that are suitable for austere and forward environments to enable earlier organism identification and resistance detection, thereby guiding targeted therapy.
Strengthen antimicrobial stewardship programs and infection prevention measures throughout the evacuation chain to limit nosocomial acquisition and onward transmission.
Ensure resilient logistics and supply chains to maintain access to effective antimicrobials and critical supplies; the authors specifically note potential advantages of innovative resupply methods, including drone-enabled medical resupply, to support operational readiness and sustain appropriate therapy in the field.
Each of these measures is framed as necessary to preserve antimicrobial effectiveness and protect both individual patient outcomes and overall force health.
The review concludes that the MDRO burden among combat casualties is increasing in both scale and severity, with clear operational, clinical, and public health consequences for LSCO and PFC. Addressing this escalation will require integrated approaches: standardized antimicrobial guidance, centralized oversight, field-capable diagnostics, robust stewardship and infection-prevention programs, and dependable logistics to deliver antimicrobials and supplies where they are needed.
Where details such as specific operational protocols, diagnostic platforms, or stewardship program structures were not provided in the source, those implementation details were not reported in the article and are beyond the scope of this summary.