Patient 43 is a 63 year-old female with MRSA prosthetic joint infection of right hip and knee.  In July 2020, the knee underwent a 2-stage revision for a MRSA infection which failed.  This was followed by a 2-stage revision of the right hip in Sep2020. Both were performed without exchange.  In Jan2021, she received hip and knee spacers since both joints continued to be culture positive for MRSA with extreme purulence.  Despite IV antibiotic treatment, the patient maintained elevated CRP/ESR markers prior to phage therapy. She began phage therapy in March 2021, when she also received a staged procedure of debridement and spacer replacement of the hip and arthrotomy/incision and drainage of the knee, each with intraoperative doses of phage. The patient received 3 days of IV phage QD. Each dose was 1.95x10⁹ PFU (10 ml of 1.95 x 10⁸ PFU/mL).  The patient had not had elevated LFTs with previous surgeries.  Her LFTs increased 2 x ULN with IA phage but then did not increase further with repeated dosing.  Her elevated CRP/ESR markers fell to normal limits after receiving phage in Mar2021. Following phage therapy the patient is to complete 4 weeks of daptomycin followed by oral Bactrim until biomarkers are within normal limits for 2 weeks.

Patient 42 is a 41 year-old female patient who underwent plastic surgical care for over 7 years. 15 years prior she had an injection of industrial silicone oil to her buttocks and lower back as part of her gender reassignment procedures. In the previous 7 years, she suffered multiple infections of the affected regions and underwent multiple long hospitalizations to treat and control these infections. Multiple debridements, local wound care, systemic antibiotic treatments and wound closures with flaps and skin grafts were required. It was not possible to truly debride the tissue since the silicone oil was diffusely infiltrated in muscles involving the thigh, gluteus maximus and lower back; most of the soft tissue of the gluteal and thigh regions had been previously debrided. Her previous infections were due to Pseudomonas aeruginosa which became resistant to all antibiotic treatments over time. Six different morphotypes were collected over the course of 6 months all with different antimicrobial susceptibility patterns. Sensitivity testing suggested synergy between a combination of P. aeruginosa bacteriophage and meropenem against these six isolates which were all present at the start of phage therapy. The patient completed 17 days of IV phage BID and had local debridement QD along with a single P. aeruginosa bacteriophage at a titer of (1x10¹¹ PFU/dose) and meropenem. Wound improvement and reduction of pain was noted on 01Feb2021 and granulation tissue was noted with reduced secretions on 09Feb2021. The first course of therapy ended on the 10th of February. With continued wound improvement post therapy, the patient received another debridement on 25Feb2021. However, by 28Feb2021 increased secretions were observed at the surgical site and additional phage were requested. An additional 8 vials were provided to continue therapy. The second course of treatment is ongoing; the patient has completed 14 days of IV phage BID and locally QD at a titer of 1x10¹⁰ PFU/dose.

Patient 41 is a 25 year-old male with no significant past medical history who sustained an extensive electrical injury on Oct2020 resulting in 22% total body surface area burns. Burn wounds were complicated by a cranial osteomyelitis with associated complicated soft tissue infection. The patient underwent extensive debridement of the scalp and skull throughout his hospital course, and ultimately underwent full thickness craniectomy with muscle flap and skin grafting in Dec2020 for definitive closure. Operative cultures from the soft tissues of the scalp and cranium grew a MDR Pseudomonas aeruginosa. The Pseudomonal isolates had increasing resistance throughout patient’s hospital course. He had previously been treated with cefepime, then imipenem-relebactam, followed by ceftazidime-avibactam. The final available Pseudomonal isolates from scalp tissue were only susceptible to Cefiderocol which the patient was started on in Dec2020 after definitive closure of the scalp wound. Since the patient was on last line antimicrobial therapy, he was started on adjunctive therapy with Pseudomonas aeruginosa-specific bacteriophage on 6Jan2021. He ultimately received Cefiderocol for 6 weeks and adjunctive bacteriophage therapy for 4 Weeks. The patient tolerated bacteriophage therapy well with no significant adverse events noted. Repeat head CT at the end of therapy showed stable post-surgical changes with no soft tissue collections or new osseous erosive changes to suggest a progressive infectious/inflammatory process. The overlying muscle flap and skin graft healed well and there was good venous and arterial signals on doppler. He was discharged to a spinal cord injury rehabilitation center in Feb2021.

Patient #40 was 74 years old with a past medical history of chronic lymphocytic leukemia, type 2 diabetes mellitus, arterial coronary sclerosis with non-ST elevated myocardial infarction who presented to the emergency department with respiratory failure due to Covid19. Other complications included septic shock with multi-organ failure, acute kidney injury and hypokalemia. Chest x-ray on 04Sept2020 showed bilateral patchy infiltrates. On 30Sep2020 a sputum culture was positive for CRAB resistant to all antibiotics except tigecycline. Phage therapy was initiated on 06Oct2020 via IV twice a day and was continued for 26 days. Eight sputum cultures were positive for CRAB from 06Oct2020 and 23Oct2020. All 6 blood cultures prior to phage therapy and the 3 following the initiation of phage therapy were negative. No adverse events were reported as related to phage therapy. The AST/ALT/ALP/TB levels were within normal ranges prior to the start of therapy on 06Oct2020. These increased beyond normal values on 01Nov2020, when the patient expired.

Patient #39 is 83 years old with a past medical history of chronic atrial fibrillation, coronary artery disease, hypertension and hyperlipidemia. On 12Oct2020 a chest x-ray showed peripheral rounded cotton ball infiltrates in the right upper lobe. Sputum culture was positive for CRAB on 19Oct2020 which was resistant to all antibiotics but showed intermediate susceptibility to tigecycline. Phage therapy IV was initiated on 22Oct2020 which was dosed twice a day. Over the next month, multiple sputum cultures were positive for CRAB and nebulized phage was added to IV therapy on 12Nov2020. A total of 50 doses of IV phage was administered over 27 days and 26 nebulized doses were administered over 2 weeks. Following initiation of nebulized phage, two negative cultures for CRAB were noted on 20Nov2020, 21Nov2020 and 26Nov2020 (but positive for Klebsiella pneumoniae and Achromobacter xylosoxidans). However, the sputum culture was positive for CRAB on 25Nov2020 and 28Nov2020. All 11 blood cultures taken during hospitalization were negative for CRAB. No adverse events were reported as related to phage therapy. Liver enzymes AST/ALT/ALP/TB were slightly elevated prior to starting phage therapy on 22Oct2020. Upon discharge on 01Dec2020 these values were still higher than normal.

Patient #38 was 89 years (Covid19 negative) with a past medical history of dementia, cerebral vascular disease and Parkinson’s disease who presented to the emergency department with respiratory distress and hypoxemia. Chest x-ray on 11Oct2020 was unchanged from previous x-rays. Sputum cultures on 21Oct2020 and 26Oct2020 were positive for CRAB and phage therapy was initiated on 28Oct2020 twice a day for 16 days. Eight sputum cultures from 28Oct2020 to 10Nov2020 remained positive. Four blood cultured taken from 21Oct2020 to 09Nov2020 were negative. One of 5 urine cultures was positive for CRAB on 21Oct2020. No adverse events were reported as related to phage therapy. The AST/ALT/ALP/TB liver enzymes were relatively normal (elevated ALP) on 24Oct2020, four days prior to phage therapy. These levels increased significantly over normal ranges on 11Nov2020 when the patient expired.

Patient #37 is 52 years old (Covid19 negative) with a past medical history of type 2 diabetes mellitus, obesity, hyperlipidemia and hypertension who was tracheostomy dependent and had multiple previous hospitalizations for diabetic foot ulcers. Upon presentation to the emergency department chest x-ray showed no acute disease. On 12Oct2020 a wound culture and sputum culture were positive for CRAB resistant to all antibiotics but demonstrated intermediate susceptibility to trimethoprim and tigecycline. Phage therapy was started on 17Oct2020 IV twice a day for 36 days. Multiple sputum cultures were positive for MDR P. aeruginosa from 22Oct2020 to 31Oct2020 and sputum culture was positive on 30Oct2020 for CRAB. Nebulized phage therapy was initiated on 02Nov2020 for five days. All phage therapy was stopped on 06Nov2020 after multiple cultures were negative for CRAB. However, sputum cultures were again positive starting on 10Nov2020 prompting re-initiation of phage therapy (IV and nebulized) on 13Nov2020 which continued until 27Nov2020. A single positive blood culture for CRAB was also noted on 02Nov2020 but 9 other blood cultures were negative from 28Sep2020 to 3Dec2020. While on the second course of phage therapy 7 sputum cultures were positive for CRAB from 07Nov2020 to 26Nov2020. Phage therapy was discontinued on 27Nov2020 after two sputum cultures were negative for CRAB on 27Nov2020 and 03Dec2020. No adverse events were reported as related to phage therapy. Liver enzymes AST/ALT/ALP/TB were elevated prior to the start of phage therapy and mostly normal on 25Nov2020 (slightly elevated ALP level), two days prior to discontinuation of phage therapy on 27Nov2020. The last AST/ALT/ALP values reported were on 07Dec2020 when they had once again increased beyond normal limits.

Patient #36 was 66 years old with a past medical history significant for major depression, anxiety, asthma, diabetes mellitus, elevated cholesterol. The patient presented with worsening shortness of breath, fever, chills and generalized weakness. Covid-19 positivity was noted since 01Sept2020. The patient had acute hypoxemia and respiratory failure secondary to Covid19 was placed on bilevel positive airway pressure. Chest x-ray on 07Sept2020 showed bilateral infiltrates. The sputum culture was positive for CRAB on 09Oct2020 resistant to all antibiotics but had intermediate susceptibility to tigecycline. Phage therapy was initiated on 14Oct20020 over 2 weeks. Twelve sputum cultures were taken between 08Sep2020 and 3Nov2020 and thirteen blood cultures were taken between 07Sep2020 and 27Oct2020. The sputum cultures were 2+ positive prior to therapy and 1+ positive for CRAB. All blood cultures were negative for CRAB. No adverse events were reported as related to phage therapy. Liver enzymes AST/ALT/ALP were within normal limits on 14Oct2020 prior to the start of phage therapy and gradually increased until 08Nov2020, the day the patient expired.

Patient #35 was 84 years old with a past medical history of dementia, hypertension, hyperlipidemia, and obesity who was admitted via the emergency department on 18Jul2020 with acute respiratory failure due Covid19. Chest x-ray showed bilateral atypical infiltrate with fibrotic scarring in the right upper lobe. Cardiac arrest occurred on 01Sept2020. The patient also had a percutaneous endoscopic gastrotomy, tracheostomy, and a large stage 4 sacral wound that required surgical debridement. On 14Sept2020 a sputum culture was positive for CRAB. Phage therapy was started on 27Sept2020 via IV twice a day for 18 days. Sputum cultures were positive for CRAB on 06Oct2020, 09Oct2020, 10Oct2020 and 11Oct2020. A wound culture on 21Oct2020 was positive for CRAB. All blood cultures were negative (9 cultures taken over 3 months from 29Jul2020 to 19Oct2020). Liver enzymes AST/ALT/ALP were elevated on 27Sept2020 prior to phage therapy and increased on 30Oct2020 when phage therapy was discontinued. The maximum values were 193 (AST) on 21Oct2020, 145 (ALT) on 21Oct2020 and 2548 (ALP) on 08Oct2020. The patient expired on 01Nov2020.

Patient #34 is 45 years old with a past medical history of Covid19, obesity, type 2 diabetes mellitus, and hypertension who was assessed in the emergency department with worsening pain due to a sacral ulcer. Chest x-ray on 11Oct2020 showed no infiltrates. Phage therapy was started on 27Oct2020 and was administered twice a day for 11 days. Wound culture on 13Oct2020 was positive for CRAB resistant to all antibiotics but demonstrated intermediate susceptibility to trimethoprim-sulbactam and tigecycline. Subsequent wound cultures on 27Oct2020, 28Oct2020, 30Oct2020, and 01Nov2020 were positive for K. pneumoniae and the wound culture on 03Nov2020 was positive for diptheroids. Liver enzymes AST/ALT/ALP/TB were within normal ranges on 05Nov2020. The patient was discharged on 06Nov2020.

Patient #33 was 57 years old with a past medical history of type two diabetes mellitus, obesity, and hypertension who presented to the emergency department in acute respiratory failure secondary to Covid19 and in diabetic ketoacidosis. The patient was ventilated on 19Jul2020.  Phage therapy was started on 12Oct2020 and was administered over 6 days. During hospitalization and prior to phage therapy, five blood cultures were taken from 19Jul2020 to 10Oct2020 and none were positive for A. baumannii. The 23Jul2020 blood culture was positive for Staph and a blood culture on 14Oct2020 following initiation of phage therapy was positive for E. faecalis. Five sputum cultures from 17Aug2020 to 10Oct2020 were positive for CRAB resistant to all antibiotics but showed intermediate susceptibility to tigecycline. No adverse events were reported as related to phage therapy. The patient expired on 18Oct2020.

Patient #32 was 54 years old with a past medical history of hypertension, elevated hyperlipidemia, muscular dystrophy, status post inferior vena cava filter placement, sick sinus syndrome and status post pacemaker, chronic obstructive pulmonary disease on home oxygen therapy, type 2 diabetes mellitus, hypothyroidism and was diagnosed with Covid19 on 13Sep2020. Upon presentation to the emergency department the patient was in acute respiratory failure with a chest x-ray showing complete opacification of the right lung and multiple patchy opacities of the left lung. The patient was ventilated on 20Sept2020. Phage therapy was started on 07Oct2020 and was administered twice a day for 28 days. During hospitalization, six blood cultures from 20Sep2020 to 31Oct2020 were negative. Thirteen sputum cultures were taken from 21Sep2020 to 5Nov2020 12 of which were positive for CRAB which were intermediate resistant to amikacin, gentamycin, and tobramycin. Sputum cultures on 02Nov2020 and 05Nov2020 were both 3+ positive upon semiquantitative culture. No adverse events were reported as related to phage therapy. Liver enzymes AST/ALT/ALP were elevated beyond normal ranges on 15Oct2020 but decreased to expected levels at the time phage was discontinued. The patient expired on 06Nov2020.

Patient #31 was 60 years old with a past medical history of hypertension, hyperlipidemia, and systemic lupus erythematosus who presented to the emergency department on 24Sept2020 with shortness of breath and a diagnosis of Covid19 from 19Sept2020. The patient was started on prednisone with minimal improvement. The chest x-ray on 24Sept2020 demonstrated bilateral infiltrates. Sputum cultures on 28Sept2020 and 08Oct2020 were positive for CRAB resistant to all antibiotics but had intermediate susceptibility to tigecycline. Phage treatment was initiated on 01Oct2020 and administered twice a day for 2 weeks. Blood cultures on 24Sept2020 and 09Oct2020 were negative. Sputum cultures were negative on 03Oct2020, 04Oct2020, 07Oct2020, and 10Oct2020. No adverse events were reported as related to phage therapy. The patient expired on 15Oct2020.

Patient #30 is 84 years old with a past medical history of dementia, hyperlipidemia, s/p pacemaker placement, cirrhosis, chronic obstructive pulmonary disease, type 2 diabetes mellitus, and hypertension with protein losing nephropathy. The patient was admitted with acute respiratory failure. Chest x-ray showed bilateral atypical infiltrates and fibrotic scarring in the right upper lobe. A urine sample collected on 20Oct2020 showed CRAB (Carbapenem-resistant Acinetobacter baumannii) infection. The patient received one dose of phage therapy and all subsequent urine, blood, wound, and sputum cultures tested negative. No adverse events were reported as related to phage therapy. The patient was discharged on 28Oct2020.

Patient #29 was a 61-year-old female with past medical history significant for hypertension, obesity who was admitted to the hospital from a nursing home with difficulty breathing for one day. Initial assessment in the emergency department found her to be in respiratory failure due to Covid19 pneumonia and in shock. She was intubated due to her respiratory issues. Phage was given in 3 IV doses administered over 2 days. Sputum culture was positive for CRAB (Carbapenem-resistant Acinetobacter baumannii) which was resistant to all antibiotics but demonstrated intermediate resistance to tigecycline and meropenem. No adverse events were reported as related to phage therapy. The patient expired prior to receiving a 4th dose on Day 3.

Patient #28 is a 58-year-old-man who has undergone two separate two-stage exchange arthroplasties for his right hip periprosthetic infection. He has undergone multiple rounds of intravenous antibiotics and oral suppressive antibiotics as well. He has developed another abscess and draining wound about his right hip. Prior to his hip surgery, he was a young, active male. Without control of this infection he would either need to undergo a resection arthroplasty which would leave him with considerable morbidity and decreased function or be at risk for developing sepsis secondary to his chronic right hip infection. APT identified a lytic S. aureus bacteriophage and provided therapy. The patient received an intraoperative phage dose followed by 7 weeks of IV bacteriophage therapy, with no reported adverse events.

Patient #27, a 61-year-old woman with several medical conditions including diabetes, sarcoidosis, VID, neuropathy, and many drug allergies and intolerances. She has struggled with recurring ear infections since 2004 and has had chronic issues with her right year. Since 2004 she has had over 10 ear surgeries for debridement and over 10 sinus surgeries to clear both a MRSA and P. aeurginosa infection of mastoid and otitis. Her revolving-door antibiotic regiment has included linezolid (potentially causing her developing optic neuritis), daptomycin (elevation of CK), vancomycin (developed severe red man), ceftraoline (developed neutropenia), also clindamycin, doxycylcline, and more recently oritavancin on and off between 2019 and 2020. Despite all these treatments the patient saw no improvement of sinus and mastoid symptoms and required frequent ENT procedures. Phage therapy began in July 2020 via IV and weekly topical doses within the sinuses. After 10 weeks of treatment, the doctor reported that the sinus looked amazing and had little secretion, which now cultured an antibiotic-sensitive Klebsiella sp.. While in November 2020 P. aeruginosa was cultured from her sinus no MRSA was found. The doctor recorded that the sinus "looked great" with no issues by the end of therapy.

Patient #26, a 60-year-old man with multiple medical comorbidities including a thoracic aortic aneurysm, atrial fibrillation status post ablation, gastric bypass surgery 2014 complicated by postop gastric sleeve strictures requiring stenting, history of DVT, and multiple joint arthroplasties including bilateral total knee arthroplasty, total hip arthroplasty (THA) and total shoulder arthroplasty. He underwent primary left total hip arthroplasty on May 27, 2014 which was complicated by methicillin resistant Staphylococcus aureus (MRSA) bacteremia and prosthetic joint infection (PJI) in 2015 and treated with debridement, antibiotics, and implant retention (DAIR) followed by chronic antibiotic suppression, which he had significant difficulty tolerating. He had a subsequent left THA revision in 2018 due to a fracture after a fall and this was complicated by recurrent infection with cultures positive for MRSA and group B strep and he underwent a repeat revision. He had continued difficulty tolerating both IV abx (daptomycin) as well as bactrim/penicillin for chronic suppression. He developed loosening of the components in late 2018. Discussions were had about possibly performing a girdlestone procedure but due to significant anticipated loss of function, this was delayed. A repeat left THA aspiration in Feb 2020 cultured MRSA. Since then he had been having intermittent fevers despite suppression with Bactrim and penicillin VK. He had two hospital admissions in February 2020 and March 2020 with drainage, erythema, fevers, and rigors, and chest pain and was wheelchair bound. The patient had multiple medical complications and did poorly with 9 or 10 out of 10 pain, intermittent fevers and chills, inability to bear weight on left leg and copious and constant brown drainage. In April, 2020 he had a DAIR procedure and received 1 dose of phage intraoperatively. His (pre-phage) intra-operative cultures were positive for MRSA and was placed on vancomycin and rifampin. He received a double dose of IA phage the next day and received ten daily (single dose) IV doses over 14 days. He did well clinically, and all drainage stopped. Re-aspiration of the joint is planned and the case is ongoing.

Patient #25, a 61 year-old male who had a primary left total hip arthroplasty in 1985 which required revisions in 1991, 2000, and 2004 complicated by infection with staphylococcus. He failed debridement, antibiotics and implant retention (DAIR) and required a two-stage exchange in 2004-2005 for Enterococcus cloacae, followed by further surgical interventions in 2008 (staphylococcus epidermidis), 2010 (staphylococcus epidermidis), 2013 with exchange of modular head due to a MSSA infection, and in 2014 with exchange of acetabular liner and modular head with insertion of antibiotic-impregnated cement due to a Enterobacter cloacae. infection. In 2016, he developed a Candida albicans infection while on chronic suppression with both minocycline and levofloxacin and had a second DAIR and on antibiotic suppressive treatment including fluconazole. In 2019, he developed a left lateral thigh fluid collection which was aspirated and grew minocycline-susceptible coagulase-negative staphylococci. He underwent a third DAIR in June 2019 and was maintained on chronic suppressive antimicrobial therapy. Despite this, the patient developed re-accumulation of fluid. Because of insufficient femoral bone stock, the only remaining surgical options were total femoral replacement done in stages which is highly morbid and unlikely to successfully eradicate the infection versus hip disarticulation. Since he had exhausted reasonable surgical and medical interventions, he was evaluated for phage therapy and the collection was aspirated (1 liter of bloody fluid) in April, 2020 which yielded a positive culture for oxacillin-resistant Staphylococcus epidermidis. Phage therapy was started intra-articularly (single dose) and daily intravenous doses x 10 days. He was maintained on levofloxacin, minocycline, and fluconazole. He did well clinically with minimal pain (this is baseline). A repeat aspiration is planned and the case is ongoing.

Patient #24, a 39-year-old female with giant cell tumor of the right distal femur treated with distal femur replacement in 2016. She developed arthrofibrosis and underwent revision in December, 2018 and developed an methicillin sensitive Staphylococcus aureus (MSSA) infection which necessitated debridement, antibiotics and implant retention (DAIR) in January, 2019. She received multiple antibiotics due to intolerability. MSSA was again isolated during a second DAIR procedure in January 2020 and she required a third DAIR procedure in January 2020. She developed increased right leg pain and night sweats in March 2020 and an increase in inflammatory markers. Phage therapy was considered as a way to mitigate the infection and possibly thwart additional surgery (resection arthroplasty which would be highly disruptive and morbid). Aspiration of the right knee on 4/3/20 showed a WBC of 10,000 per cubic millimeter with 89% neutrophils and the culture was positive for MSSA. She was started on phage therapy on 4/3/20. She received a double dose IA and daily IV dosing. She did well clinically and reported 0 out of 10 pain. She is scheduled for repeat aspiration and the case is ongoing.

Patient #23, a 73 year-old male with Type 2 diabetes mellitus, hypertension and severe peripheral vascular disease including a left femoral-popliteal bypass with vascular graft, left superior femoral artery and popliteal atherectom, left femoral profunda endarterectomy with patch angioplasty, left lower superior femoral artery stent and right femoral to left popliteal bypass. In January 2020, his surgical wounds broke down at both right femoral and left popliteal incisions. The wounds were noted to be non-purulent with sinus tracts probing to graft. Culture at both sites grew carbapenem resistant Klebsiella pneumonia and he also had a pseudoaneurysm at the right femoral anastomosis. Blood cultures were negative and there was no fever or leukocytosis. He was treated with multiple antibiotics from 17January to 4March, 2020. Exgraftment of the infected graft was considered with axillary-femoral graft bypass but patient refused this procedure. Even if he had accepted to undergo the procedure, the new graft would have had to be placed into an infected wound bed. Instead, he underwent a right femoral exploration with sartorius muscle flap closure to reduce the risk of spontaneous rupture of the pseudo-aneurysm. In January 2020, he was found to have new cardiomyopathy with severely reduced ejection fraction. The patient was told that the likelihood of cure with antibiotics alone was remote. He was treated with phage therapy (19 doses) starting on 2March, 2020. No adverse events were reported during treatment. In April 2020 he was noted to have left leg gangrene of first and second toe and occlusion of left common iliac artery. Despite these complications, he has reported no fevers or other signs and symptoms of systemic infection. He was also found to have greenish discharge from his left popliteal wound which was open since his initial evaluation in January 2020 and healing of his right groin wound. In May 2020, he had worsening pain in left foot and left calf which has prevented him from walking or sleeping well. At this point, the culture obtained in April showed Pseudomonas aeruginosa and was admitted for IV antibiotics and clearance for surgery. Cefepime was initiated from admission and continued to date. Due to his cardiac risks, he was transferred to another hospital for cardiac optimization before proceeding with the left above-knee-amputation. During this admission, he remained afebrile, without leukocytosis or other signs and symptoms of systemic infection. He is scheduled for vascular surgery and this case is ongoing.

Patient #22, a 69 year-old woman with a past medical history of chronic kidney disease, hypothyroidism, severe congestive heart failure with reduced ejection fraction, prosthetic knee joint infection, and a history of bacteremia. In November 2016, she had a left ventricular assist device (LVAD) placed and a right knee arthroplasty. Over a 4 year period she developed multiple infections of her LVAD driveline and prosthetic joint infections resistant to multiple antibiotics. In June 2019 she had a right knee incision and drainage procedure and a 1-stage revision. Her LVAD driveline was also debrided, she was discharged to rehabilitation on ceftolozane-tazobactam for a P. aeruginosa in her drive line and right knee and oral amoxicillin for E. faecalis in her drive line. Meropenem was added in June 2019 because her driveline isolate was resistant to ceftolozane-tazobactam. She had recurrent P. aeruginosa bacteremia in December 2019 after stopping ceftolozane/tazobactam (by her choice) in November 2019. These P. aeruginosa isolates had similar susceptibilities to those isolated in June 2019. Three P. aeruginosa isolates (from blood, right knee and drive line) were tested for phage susceptibility. Two matching phage were provided in February 2020 and the patient received her first phage intravenously along with ceftolozane/tazobactam and oral amoxicillin. Her C-reactive protein levels fell from 61 to 31.7 over her 3 weeks and her erythocyte sedimentation rate decreased from 104 to 89. Her LFTs were normal during most of her phage therapy, although she was noted to slightly increase in March 2020. Soreness in her knee joint decreased during her four weeks phage course. She was able to walk more on her knee and has had minimal driveline drainage. This case is ongoing.

Patient #21, a 69 year-old male with a history of ischemic heart disease and non-insulin-dependent diabetes mellitus.  He was admitted in November 2019 with malignant otitis and mastoiditis on his left ear due to Pseudomonas aeruginosa. The patient was discharged on Dec 1st and readmitted with the same issue on Dec 8th suggesting failure on antibiotics.  On Dec 19th, he had a left radical mastoidectomy. Antibiotics were started postoperatively and phages were added 2 days later. Phages were given intravenously for 2 weeks and ceftazidime was administered for 6 weeks. No adverse events were observed during therapy and his treatment provided a good response. During a follow visit on 26Jan2020 he was noted to have good closure of the surgical wound.

Patient #20 was a 10 year-old female with an inherited genetic dilated cardiomyopathy and had a Berlin heart inserted in January 2019. She had a prolonged hospital course that included colonization with Klebsiella pneumoniae and Pseudomonas aeruginosa, Clostridum difficile toxin-associated colitis and almost persistent bacteremia with P. aeruginosa. She recieved seven weeks of a single bacteriophage therapy intravenously and meropenem. She had a decline in her health while on treatment and experineced high fevers and decreased level of consciousness and both phage ane merepenem were discontinued. Alhough her daily cultures were negative and inflammatory markers remained within normal limits, phage and meropenem therapy was stopped due to high fever and major reduction in neurological response. After discontinuation of therapy, her cultures were positive for MDR P. aeruginosa and had the same antibiotic susceptibilities as her original cultures. Due to low consciousness level, with no known source of her resistant infection, failure to gain weight and tolerate feeds, her parents asked to discontinue suportive therapy and she passed away in January 2020.

Patient #19, a 7-year-old female who sustained multiple injuries from a MVA in 2018. This accident led to a long hospital admission and multiple surgical interventions with metal hardware (bilaterally, from hips down) ultimately resulting in chronic multidrug resistant P. aeruginosa osteomyelitis of the left foot. Her physicians sought out phage therapy since futher surgery might destabilize the ankle joint resulting in amputation. Patient completed 2 weeks of therapy with a single phage. Two weeks after discharge her physician reported healing at the site of infection and increased mobility.

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), and 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.

Patient # 17 is a 61-year-old female with a chronic, persistently infected right prosthetic knee joint infection with methicillin-sensitive S. aureus (MSSA) present since Dec 2017. It remained infected with draining sinuses despite multiple rounds of IV antibiotics and surgeries. She received two weeks of phage therapy IV twice a day provided by another company and clinically responded. However, a few weeks after stopping phage her infection recurred and this company was not able to supply additional phage. The patient had since developed anti-phage neutralizing antibodies which neutralized 4 APT phage candidates. At the time of surgical debridement, hardware removal, and antibiotic spacer placement on 25September, 2019 and received an intra-operative dose of a single lytic phage. Multiple surgical cultures (surgical) were positive for MSSA. The patient continued and tolerated twice daily IV phage for 4 weeks using this phage and conducted home installation without adverse event. She responded clinically to combined phage and antibiotic therapy and experience a reduction in inflammatory markers (ESR, CRP). However, she subsequently developed recurrent swelling of the right knee for which she underwent aspiration of the knee joint. Synovial fluid was culture negative on 1Nov2019 and had minimal inflammatory cells. Phage was discontinued on 6Nov2019 and IV cefazolin was continued. She was admitted for a fall on November 17, 2019 and was diagnosed with a right hip fracture which required an open reduction and internal fixation. Her right knee was also more swollen and painful since the fall and synovial fluid analysis on 17Nov2019 showed 25,000 WBC/mL with 92% polymorphonuclear cells. On November 22, 2019 her physician reported that the S. aureus infection had cleared but the synovial fluid from the same knee was now culture positive for pan-susceptible P. aeruginosa. The patient received IV cefepime for the P. aeruginosa infection, though the treating physician requested a P. aeruginosa phage for treatment as well. The first dose was administered on February 12th intra-op followed by twice daily IV installations for one week. All her surgical cultures from 12Feb2020 were negative. No adverse events were reported during the treatment.

Patient #16, a 45-year-old woman who underwent a liver transplant leading to septic shock from intra-abdominal infection. She underwent liver transplantation in April 2019 which was complicated by delayed closure, biliary leak, peritonitis, and ischemic bowel s/p multiple resections. Her abdomen was closed using mesh which developed DIC and bleeding. This infection was colonized with Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterococcus faecium. The VRE was addressed with an antibiotic regimen and the patient received two phage P. aeruginosa and Klebsiella. The patient had noticeable improvement after the first few doses of the P.aeruginosa phage, but this improvement was overshadowed after the administration of the second phage. Observed phage interactions within the HRQT suggests that the K. pneumoniae phage inhibited the P.aeruginosa phage from attacking the patient bacteria. The patient was moved to comfort care after she suffered multiple system organ failure.

Patient #15, a 46-year-old male who had multiple trauma 25 years ago during his service in the military. During this time, he had multiple prolonged admissions to the hospital where he eventually developed Pseudomonas aeruginosa osteomyletis in his left tibia. The most recent imaging at the site of infection suggested that the P. aeruginosa had spread up and down from original site. Patient received 2 weeks of phage therapy at titer of 1.3e11 PFU/ml, at 170 EU/mL and ceftazidime. Patient was released from the hospital with reduced lymphocyte count, and mild elevation of CRP.

Patient #14, a 61-year-old male who suffers from bilateral knee osteoarthritis. In 2008, the patient had a right TKA which was complicated by several infections between 2009-2018 (treated with I & D and intensive antibiotic regimen), which lead to a spacer removal and replacement of the distal femoral modular component within the knee in 2019. At the site of surgery, his right knee became infected with an MDR, Klebsiella pneumoniae. The patient received 6 weeks of phage therapy via IV at a titer of 5e10 and ~20 EU/mL and experimental antibiotic cefidericol. The swelling seen at the site of infection dramatically decreased after the first infusion and at the end of therapy the patient had significant improvements in mobility, and blood testing results.

Patient #13, a 10-year-old female diagnosed with cystic fibrosis, who was admitted to the hospital for CF exacerbation with an Achromobacter xylosidans infection resistant to all available antibiotics. The patient was initially treated with the experimental antibiotic cefiderocol and 17 days later she began her phage therapy. During the first 5 days of phage therapy, the patient received both cefiderocol and phage. On the 5th day of the joint treatment the antibiotic regimen was stopped, and phage therapy continued. The patient received a single phage for therapy via IV with a titer of 2.35x10^9 PFU/mL and was released from hospital with significant clinical improvement.

Patient #12, a 36-year-old male who, due to a spinal injury, is an incomplete quadriplegic and has an ileal conduit. For over a year, he suffered from recurrent urinary tract infections (RUTI) and bacteremia caused by an extended spectrum beta-lactamase (ESBL) producing strain of Escherichia coli. His phage therapy began February consisted of two different phage products with titers between 1.0 x 10^8 and 7.0 x 10^ 8 PFU/mL. The treating physician administered the phage products twice daily intravenously during weekdays and directly into the patient's ileal conduit once per week. The patient began receiving antibiotics during their phage therapy to address sacral ulcer. At the doctor's request, therapy was stopped after 13 doses as the patient was now culture negative. The patient remained culture negative for two months but was readmitted into the hospital with reoccurring symptoms.

Patient #11, a 23-year-old male with cystic fibrosis who developed a multidrug resistant Burkholderia gladioli infection in his chest cavity prior to a lung transplant in 2017. Since the transplant, the patient suffered from a sternal wound infection and recurrent bacteremia caused by the same bacterial pathogen. Phage therapy was initiated in early November 2018. The doctor reported marked clinical improvement after 11 days of treatment. After 35 doses of phage therapy, the patient had significant radiological improvement and was culture negative.  Patient is stable with significant clinical improvement of his sternal wound and has remained culture

Patient #10, a 47-year-old male who suffered from significant head trauma after a motor vehicle accident. He was initially treated for a subdural hematoma, but soon after receiving surgery for facial fractures, he developed an abscess and ventriculitis caused by a multidrug resistant strain of Acinetobacter baumannii. The patient was in critical condition with dangerously high bacterial titers detected in his cerebral spinal fluid (CSF) prior to phage therapy. Treatment consisted of one phage strain administered intravenously starting in early November 2018. After 8 days of treatment, the patient’s CSF was culture negative for the MDR A. baumannii, however, he was culture positive for a strain of Klebsiella pneumoniae and Staphylococcus aureus. The patient’s physician reported brain death and announced deceased mid-November 2018.

Patient #9, an 18-year-old female who underwent a kidney transplant in March 2018 which prompted multiple episodes of bacteremia and urosepsis caused by an extended spectrum beta-lactamase (ESBL) producing strain of Escherichia coli. Phage therapy consisting of two different phage products with titers ranging from 1.0 x 10^9 to 1.0 x 10^10 PFU/mL was first administered intravenously in mid-September 2018. At this time the patient was still receiving standard of care antibiotics. The patient ended the course of antibiotics 15 days after start of phage therapy. The patient continued to received phage therapy. She was afebrile and showed marked clinical improvement after one week of treatment without antibiotics. The patient received phage therapy for a total of 23 days and was confirmed culture negative 11 days thereafter

Patient #8, a 28-year-old female with cystic fibrosis who developed a multidrug resistant Burkholderia dolosa infection in her lungs after having a bilateral lung transplant in early 2018. Despite multiple courses of antibiotics, the patient continued to deteriorate. Phage therapy was initiated in early September and additional doses were supplied in mid-September and early October. The patient’s bacterial titer dropped significantly, and the physician reported minor clinical improvements after 34 days of treatment. However, the patient suffered from an unrelated splenic pseudoaneurysm, and underwent a splenectomy and distal pancreatectomy at the end of October 2018. Despite a brief clinical hold, phage therapy was resumed in mid-November 2018. The patient’s physician reported that her infection had disseminated and decided to cease phage therapy in late November 2018. The patient was reported deceased late December 2018.

Patient #7, a 41 year old male who sustained multiple traumas including the left knee. He developed a post-operative wound infection with multidrug resistant Klebsiella pneumoniae and Acinetobacter baumannii. A second muscle flap surgery was performed in a final attempt to save the patient’s leg. Following surgery, the patient received a two week course of intravenous bacteriophage therapy. His wound drainage became culture negative, and the muscle flap healed completely. He was discharged from the hospital and avoided above knee amputation.

Patient #6, a 60 year old male with a left ventricular assist device infected with multidrug resistant Pseudomonas aeruginosa. His blood cultures were positive. He received 6 weeks of an intravenous bacteriophage mixture containing three phage. Phage was provided to the patient in four shipments. Drainage from the device became significantly less, and the patient eventually became culture negative. This case was a pioneer for the use of outpatient intravenous phage in the home without sequelae.

Patient #5, a 25 year old female with cystic fibrosis. She had a long history of multidrug resistant Burkholderia cenocepacia in her sputum. Despite her history, she was able to find a surgeon willing to perform a double lung transplant. Her post-transplant course was complicated by a re-emergence of the multidrug resistant Burkholderia cenocepacia in her blood, pneumonia and deteriorating respiratory status. The patient received two doses of intravenous bacteriophage therapy. She continued to decompensate over the next few hours and passed away due to progressive respiratory failure.

Patient #4, a 67 year old male with a history of hypersensitivity pneumonitis and pulmonary fibrosis. He underwent bilateral lung transplantation in October 2016. His post-transplant course was complicated, including the development of two episodes of multidrug resistant Pseudomonas aeruginosa pneumonia. Bacteriophage therapy was administered via nebulizer and intravenously, along with adjunctive systemic antibiotics. Therapy was well tolerated without any attributable adverse events. Both episodes of pneumonia resolved, and the patient’s respiratory status improved. Patient was discharged from the hospital infection-free.

Patient #3, a 77 year old male, suffered a traumatic brain injury. He developed a craniectomy site infection with multidrug resistant Acinetobacter baumannii. Intravenous bacteriophage therapy was administered for 8 days. The patient initially seemed more alert, but fever and leukocytosis persisted. The craniectomy site and skin flap healed well. Before receipt of the second phage cocktail, the patient’s family decided to withdraw care, and the patient died. This was published in the journal Open Forum Infectious Diseases as “Phage Therapy for a Multidrug-Resistant Acinetobacter baumannii Craniectomy Site Infection” (LaVergne 2018).

Patient #2, a 2 year old male with a history of DiGeorge Syndrome and complex congenital heart disease. Following cardiac surgery, he developed a recalcitrant multidrug resistant Pseudomonas aeruginosa bacteremia. Bacteriophage therapy was initiated intravenously, but then held due to progressive heart failure. Despite premature cessation of therapy, blood cultures obtained 4 and 5 days subsequently were sterile. Therapy was resumed 11 days after cessation, and blood cultures that had become positive reverted back to sterile. Unfortunately, the patient decompensated, presumably due to progression of undrained fluid collections, antecedent influenza infection, and end-stage cardiac failure. This case was published in the Journal of Pediatric Infectious Diseases Society as “Refractory Pseudomonas Bacteremia in a 2-Year-Old Sterilized by Bacteriophage Therapy” (Duplessis 2017).

Patient #1, Tom Patterson, a 68 year old male, developed a multidrug resistant Acinetobacter baumannii infected pancreatic pseudocyst. Despite multiple antibiotic courses, the patient deteriorated over a four month period and became comatose. Bacteriophage therapy was administered. A marked improvement in the patient’s condition was observed within 48 hours of starting intravenous therapy. Following 11 weeks of therapy, the patient made a full recovery. This case was published in the journal Antimicrobial Agents and Chemotherapy as “Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails to Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection” (Schooley 2017).