The journal Antibiotics describes* a clinical case of successful treatment with bacteriophages of a chronic joint prosthesis infection caused by methicillin-resistant Staphylococcus aureus (MRSA)

A 72-year-old obese man (BMI 41) with hyperlipidemia was hospitalized with chronic MRSA infection of his knee prosthesis. Twenty years earlier, he had septic arthritis and an intraosseous abscess of the right knee caused by methicillin-sensitive staphylococci, which was treated with intravenous cefazolin. One year later, the patient suffered a distal femur fracture that required lateral plate fixation. He later developed severe osteoarthritis and underwent right knee arthroplasty in 2012. In 2014, the patient developed a Staphlylococcus epidermidis infection of the joint prosthesis and underwent open debridement (DAIR), followed by a two-stage revision after recurrent infection. In 2016, a right knee injury resulted in erythema and effusion, and arthrocentesis revealed MRSA. A DAIR was performed, followed three weeks later by a second one due to worsening symptoms. Therapy with intravenous and intra-articular (i.v.) vancomycin was initiated. After five weeks, vancomycin was replaced with intravenous daptomycin, and the i.v. vancomycin was continued for three weeks. The patient was then switched to oral doxycycline, which lasted for two years and successfully suppressed MRSA. Three weeks after completing the doxycycline course, a relapse occurred, and arthrocentesis again revealed MRSA. Symptoms worsened with doxycycline, which was reintroduced. Due to the aforementioned distal femur fracture, which had never fully healed, a two-stage joint revision was not possible, and the patient refused amputation. The patient was offered DAIR with the use of bacteriophages intravenously and intrasternally.

MRSA strains isolated from the joint were sent to a commercial laboratory for selection of specific phages with high lytic activity. During DAIR, multiple fistulas, significant soft tissue damage, extensive suppuration, erosion of the distal femur, and significant damage to the prosthesis, which was beyond repair, were identified. Upon completion of the DAIR, the patient received intravenous bacteriophages (5.4 x ¹⁰ PFU in 10 mL of saline). A course of daptomycin 1000 mg intravenously daily was then started, followed by a daily course of intravenous bacteriophages the following day (2.7 x 10 ^PFU in 50 mL of saline).

Read also: Bacteriophages in the treatment of infective endocarditis of a prosthetic valve

After the third dose of intravenous bacteriophages, the patient experienced a sharp increase in liver transaminase levels (AST) and ALT: 136-fold and 86-fold, respectively. The following day, transaminase levels increased further, and bacteriophage therapy was discontinued. Bilirubin, alkaline phosphatase, creatine kinase, and prothrombin time were normal. Infectious liver lesions were excluded. An ultrasound revealed hepatomegaly, but no other liver pathologies were detected. The daptomycin course was extended to 6 weeks. AST and ALT levels returned to normal 10 days after the initial increase.

Three weeks after discontinuing antibiotic therapy, the patient underwent debridement. No signs of active infection were observed, and microbiological analysis of various tissues showed no infection. A static spacer containing vancomycin was inserted, and an intravenous injection of bacteriophages (2.7 x 10 ⁹ PFU in 10 ml of saline) was administered. AST and ALT monitoring for 5 days showed no increase.

Two months later, after his BMI had normalized, the patient underwent implantation of a megaprosthesis. He also received intravenous bacteriophages (2.7 x 10 ⁹ PFU in 10 ml of saline). Bacterial culture results from the surgical site were negative. A week later, the patient was discharged from the hospital and referred for rehabilitation.

Joint prosthesis infection (infectious arthritis of the artificial joint) is one of the most common complications after joint replacement (occurring in 1-2% of artificial prostheses), with high mortality rates (over 20% within 5 years). Joint prosthesis infection is difficult to treat due to the formation of bacterial biofilms on the surface of the prosthesis. Effective destruction of bacteria in biofilms requires antibiotic concentrations 1,000 times higher than those used to kill individual (planktonic) bacteria. Therefore, the search for new treatments for joint prosthesis infections, as well as other infections associated with biofilm formation, is highly relevant.

A promising method for treating antibiotic-resistant infections, particularly those associated with biofilms, is bacteriophages – bacterial viruses that specifically destroy certain types (strains) of bacteria, including those in biofilms, without affecting the body's normal microflora.

* Doub JB, Ng VY, Johnson AJ et al. Salvage Bacteriophage Therapy for a Chronic MRSA Prosthetic Joint Infection // Antibiotics 2020, 9 (5), 241; https://doi.org/10.3390/antibiotics9050241