We report our clinical experience treating a critically ill patient with polymicrobial infections due to multidrug-resistant Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa in a 56-year-old woman who received health care in India and was also colonized by Candida auris . A precision medicine approach using whole-genome sequencing revealed a multiplicity of mobile elements associated with NDM-1, NDM-5, and OXA-181 and, supplemented with susceptibility testing, guided the selection of rational antimicrobial therapy.