Patient #18, a 71-year-old male with a morbid obesity (BMI 41) and hyperlipidemia presented with a chronic MRSA PJI. Twenty years prior he had a methicillin sensitive Staphylococcus aureus (MSSA) septic arthritis and intraosseous abscess of his right knee that was treated with intravenous (IV) cefazolin. One year later, he fractured his distal right femur, requiring open reduction and internal fixation with a lateral plate. He developed severe osteoarthritis over the subsequent decade, had a right knee arthroplasty in 2012 and a Staphylococcus epidermidis right knee PJI in 2014 which required debridement, antibiotics, and implant retention (DAIR), an a subsequent 2-stage revision. After a fall in 2016, he developed an MRSA infection and underwent two DAIR procedures. Multiple antibiotics were administered and he was transitioned to chronic oral doxycycline therapy. Once this was discontinued, his infection recurred and repeat arthrocentesis culture grew MRSA. Despite resumption of doxycycline, symptoms worsened. Since his distal femur fracture had healed poorly, a standard 2 stage revision was deemed not feasible and the patient refused amputation. Instead, he had a DAIR with IA and IV bacteriophage therapy. Intraoperatively, numerous sinus tracts, gross purulence, and extensive soft tissue infection were present. Extensive erosion of the distal femoral bone stock was present, and gross loosening of the prosthesis was evident. Therefore, prosthesis could not be salvaged. Explant of prosthesis components with placement of static vancomycin and tobramycin spacer was conducted. To allow for femoral reconstruction, clearance of the extensive MRSA infection was required. After surgery, he received two doses of IA bacteriophage, IV daptomycin and was started on daily phage therapy the next day. After the third IV dose of bacteriophage, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) increased to 136 and 86. The next day, AST and ALT were 692 and 462 and bacteriophage therapy was discontinued. Bilirubin, PT/INR, alkaline phosphate, and creatine kinase remained normal. Albumin decreased to 2.7 from baseline of 3.6, as had occurred with his numerous previous surgeries. Daily cumulative doses of Tylenol were less than 1.5 grams. Hepatitis A, B, and C serologies were negative. Tests for influenza, adenovirus, parainfluenza, enterovirus, RSV, EBV, CMV, mycoplasma, chlamydia, and coronavirus were negative. Ultrasound showed hepatomegaly, but no ductal or other abnormalities were seen. AST and ALT decreased to normal 10 days later. CRP trended to normal 14 days after surgery. IV daptomycin was continued for 6 weeks, and then antibiotics were stopped. Three weeks off antibiotics, the patient underwent a second debridement surgery to confirm clearance of infection and had resection of the grossly malunited distal femur fracture and heterotopic bone. Another static vancomycin spacer was inserted. No infection was seen operatively, but another IA bacteriophage dose was given. Eight cultures from soft tissues, femoral canal, and devitalized bone were all negative. Daily monitoring for 5 days showed no elevations in AST or ALT. Two months later, after optimization of BMI, implantation of a cemented distal femoral megaprosthesis was performed off antibiotics. Given the severity of the previous infection, an additional IA bacteriophage dose was given. Intraoperative cultures were again negative. No elevations in AST or ALT were observed. One week later, the patient was discharged to receive rehabilitation to strengthen his right lower extremity.