Since its identification as a unique species in 1982, Escherichia hermannii has been implicated as a pathogenic organism in very few cases of human disease. Our report discusses a case of bacteremia with Escherichia hermannii identified by Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and RapID™ ONE analysis in a patient getting TPN through a peripherally-inserted CVC (PICC). The PICC was removed. The bloodstream infection was successfully treated with empiric piperacillin-tazobactam, which was then narrowed to trimethoprim-sulfamethoxazole based on sensitivity data for a 14 day course of antimicrobial therapy. E. hermannii's association with bloodstream infection in patients with central venous catheters supports data implicating biofilm formation as a key pathogenic feature of E. hermannii. Of the 9 previous cases of E. hermannii infection reviewed in the literature, 4 cases occurred in immunocompromised hosts, 2 were associated with trauma or injection, 2 were associated with central lines, and only one case had no identifiable risk factor. E. hermannii appears to act as an opportunistic pathogen, causing disease in an immunocompromised host or through a central access catheter, injection, or trauma. E. hermannii likely causes catheter-related bloodstream infections in these hosts through biofilm formation, demonstrating the importance of catheter removal in addition to antimicrobial therapy in the treatment of these infections.