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Enteric fever is a potentially fatal multisystemic illness caused primarily by Salmonella typhi and, to a lesser extent, by Paratyphi A, B, and C. Emergence of resistance has depleted the antimicrobial arsenal overtime, making treatment challenging and costly. In 2016, a new extensively drug resistant (XDR) strain of Salmonella typhi emerged in Sindh, which only responds to two antibiotics--carbapenems and azithromycin. Its clinical spectrum is not yet clear but increased morbidity and mortality is being observed with it. We present a severe case of XDR Salmonella typhi where the clinical course was complicated by delayed defervescence, severe hepatitis, soft tissue infection, and profuse lower gastrointestinal bleeding, which responded to a combination of carbapenem and azithromycin and an invasive procedure to contain bleeding from the cecal artery. The purpose of this case report is to highlight the morbidity, cost, and therapeutic challenges associated with severe XDR Salmonella typhi infection., Competing Interests: The authors have declared that no competing interests exist.