Case Presentation: A 59-year-old man with a history of long-term tobacco use, alcohol use disorder, hypertension, and left total knee arthroplasty (TKA) 30 years prior presented with a recurrent left knee infection. He initially developed MRSA septic arthritis in October 2023 and underwent prosthesis removal with antibiotic spacer placement, followed by a course of daptomycin, followed by linezolid when his treatment became complicated by daptomycin-induced eosinophilic pneumonitis. After clearance of the MRSA infection, he underwent TKA revision six months later. One month post-revision, he returned with painful swelling and malodorous purulent wound drainage. Operative debridement, fasciocutaneous flap placement, and split-thickness skin grafting were performed. Initial cultures were negative, but repeat anaerobic broth cultures grew Bifidobacterium species. Examination showed superficial wound breakdown with intact fascia and no evidence of periprosthetic involvement. Given literature suggesting resistance of Bifidobacterium to metronidazole and meropenem, he was treated with linezolid and amoxicillin-clavulanate for seven days [1]. After more than one year without orthopedic follow-up, he re-presented without local or systemic evidence of infection.

Discussion: Bifidobacterium spp. are anaerobic, gram-positive rods commonly considered beneficial components of the gut microbiome but can become opportunistic pathogens when microbial balance is disrupted [2,3]. Reported cases of invasive bifidobacterial disease typically involve probiotic use, gastrointestinal pathology, or immune compromise; prosthetic joint infections (PJI) caused by these organisms are exceedingly rare [4,5,6]. Their slow growth, anaerobic requirements, and frequent coexistence with more readily cultured pathogens may lead to under-recognition in musculoskeletal infections [7]. In this case, Bifidobacterium was isolated only on repeat anaerobic broth culture, emphasizing the need for extended incubation and broad diagnostic consideration when initial cultures are negative. Unlike hematogenous PJI, which typically presents with systemic illness and requires prolonged antimicrobials, this patient’s superficial infection responded to short-course therapy, though poor follow-up limits a definitive assessment of long-term outcomes [8,9].

Conclusions: This case highlights the pathogenic potential of Bifidobacterium spp. in postoperative wound infections and underscores the importance of suspecting anaerobic organisms when cultures are negative. Clinicians should recognize Bifidobacterium as a possible pathogen even in patients without probiotic exposure or immunocompromise and consider its unique antimicrobial susceptibilities when selecting therapy. Greater awareness of these atypical organisms may improve diagnostic accuracy and management of suspected PJI and postoperative wound complications.