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The objective of this study is to identify the risk factors related to colonization or infection in an outbreak of multidrug-resistant Klebsiella pneumoniae in a burn patient unit. The authors studied the risk factors associated with colonization or infection using a case-control study design involving patients with multidrug resistant K. pneumoniae (n = 26) and controls (n = 50). They describe the outbreak and provide a retrospective analysis that encompasses patient demographics, microbiological isolation, culture sites, burn features, inhalation injury, biomarkers (lactate and N-terminal probrain natriuretic peptide), general illness severity scores (Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment), burn-specific severity scores such as the Abbreviated Burn Severity Index (ABSI), length of stay, and mortality. Patients colonized with multidrug-resistant K. pneumoniae were older (55 vs 42 years), presented with larger burns (32 vs 18% of BSA), and more frequently had full-thickness burns (53 vs 22%). They also had higher ABSI, Acute Physiology and Chronic Health Evaluation II, and Sepsis-related Organ Failure Assessment scores, and they required more days of mechanical ventilation and longer stays in the critical burn unit. Multivariate analysis showed that the factors most significantly related to the development of infection or colonization with K. pneumoniae were burns located on head and neck (odds ratio, 4.81) and the ABSI score (odds ratio, 1.66). Control of the outbreak was achieved by enforcing contact precautions and extensive cleaning. An elevated ABSI score and burns located on the head and neck were the risk factors most significantly related to colonization or infection in an outbreak of multidrug-resistant K. pneumoniae in a critical burn patient unit.