Multidrug-Resistant Organisms in Combat-Related Injuries: Insights from Iraq, Afghanistan, Ukraine, and Implications for Large-Scale Combat Operations.

INTRODUCTION: Armed conflict is a powerful driver of antimicrobial resistance, and combat-related infections caused by multidrug-resistant organisms (MDROs) have emerged as a defining challenge of modern military trauma care. Reports from Iraq, Afghanistan, and the ongoing conflict in Ukraine document a clear progression from multidrug-resistant to extensively drug-resistant (XDR) and pan-drug-resistant (PDR) pathogens. This review synthesizes current evidence on combat-related MDRO infections during large-scale combat operations (LSCO) and prolonged field care (PFC). METHODS: A narrative literature review was conducted using MEDLINE/PubMed for English-language publications from January 2008 through April 2026, combining the terms war, armed conflict, combat injury, Iraq, Afghanistan, Ukraine, antimicrobial resistance, and multidrug-resistant organisms. Eligible sources included peer-reviewed original research, systematic and narrative reviews, and military clinical guidelines. Standard consensus definitions were used for MDR, XDR, and PDR. RESULTS: Combat-related infections are predominantly polymicrobial and dominated by Gram-negative bacilli, particularly Acinetobacter baumannii, Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales. The Trauma Infectious Disease Outcomes Study (TIDOS) demonstrated MDR Gram-negative infection in approximately 27% of infected casualties from Iraq and Afghanistan. Surveillance from Ukraine reveals a qualitative escalation: meropenem resistance reaches 72% in A. baumannii and 83%-91% in K. pneumoniae, with co-production of NDM-1, OXA-48, and KPC-2 carbapenemases, frequent resistance to last-line agents (cefiderocol, ceftazidime-avibactam), and convergence of resistance and hypervirulence in international high-risk clones. Frontline wound cultures suggest that MDR acquisition is predominantly nosocomial, occurring along the evacuation chain rather than at the point of injury. Repatriation of foreign combatants colonized by XDR organisms now represents an unprecedented international dissemination risk. CONCLUSIONS: The MDRO burden in combat casualties is escalating in scale and severity, with direct implications for LSCO and PFC. Mitigation requires standardized antimicrobial protocols across Role 1 and Role 2 levels of care, centralized oversight by the Defense Health Agency, deployable rapid diagnostics, robust stewardship and infection-prevention programs, and resilient logistics-including drone-enabled medical resupply-to maintain antimicrobial effectiveness and operational readiness.