Clinical Report: Successful Treatment of Prosthetic Joint Infection with Phage Therapy

Background

Prosthetic joint infections (PJIs) caused by multidrug-resistant (MDR) organisms present major therapeutic challenges and may require prolonged, complex treatment. Klebsiella pneumoniae can form biofilms and develop extensive antimicrobial resistance, limiting treatment options. Phage therapy has re-emerged as a potential adjunctive treatment for MDR infections, particularly when conventional therapies fail.

Data Highlights

• The patient was a 52-year-old man with multiple war-related injuries who underwent total elbow arthroplasty and subsequently developed a prosthetic joint infection caused by MDR K. pneumoniae.

• The patient received a 14-week regimen of cefiderocol, fosfomycin, ertapenem, and colistin with repeated surgical debridement after an initial 4 weeks of intravenous antibiotics.

• During combined phage-colistin treatment, relative bacterial load decreased by 3.52 log and K. pneumoniae became undetectable by day 8; cultures on days 12 and 15 were negative.

• Intravenous phage therapy was continued for a total of 56 days, with local administration during the first 5 days.

Key Findings

• The infecting K. pneumoniae strain harbored extended-spectrum β-lactamases and the OXA-48 and New Delhi metallo-β-lactamase carbapenemases.

• Multiple antibiotics and repeated surgical debridement achieved only temporary microbiological clearance, with signs of recurrent infection appearing in March 2024.

• A personalized lytic phage demonstrated high activity against all 6 K. pneumoniae isolates obtained from the patient and was administered with colistin and surgical debridement.

• Combined treatment was associated with progressive wound healing, partial recovery of elbow mobility, and sustained negative microbiological monitoring during available follow-up.

• No adverse effects were reported, and C-reactive protein, glomerular filtration rate, and white blood cell counts remained stable during treatment.

Clinical Implications

This case supports the potential role of personalized phage therapy as an adjunct to antibiotics and surgical debridement in complex prosthetic joint infections caused by highly drug-resistant pathogens when conventional treatment options are limited. The authors emphasize that well-designed clinical trials are needed to validate efficacy and implementation in routine clinical practice.

Related Resources & Content

1. Phage Therapy in the Postantibiotic Era — Gordillo Altamirano FL, Barr JJ; Clinical Microbiology Reviews; 2019; 32; DOI: 10.1128/CMR.00066-18.

2. Phage Therapy as a Novel Therapeutic for the Treatment of Bone and Joint Infections — Suh GA, Ferry T, Abdel MP; Clinical Infectious Diseases; 2023; 77:S407-S415; DOI: 10.1093/cid/ciad533.

3. Combination of Pre-adapted Bacteriophage Therapy and Antibiotics for Treatment of Fracture-Related Infection Due to Pandrug-Resistant Klebsiella pneumoniae — Eskenazi A, Lood C, Wubbolts J, et al; Nature Communications; 2022; 13:302; DOI: 10.1038/s41467-021-27656-z.

4. Targeted Phage Hunting to Specific Klebsiella pneumoniae Clinical Isolates Is an Efficient Antibiotic Resistance and Infection Control Strategy — Ferriol-González C, Concha-Eloko R, Bernabéu-Gimeno M, et al; Microbiology Spectrum; 2024; 12:e0025424; DOI: 10.1128/spectrum.00254-24.

5. Drug Treatments for Prosthetic Joint Infections in the Era of Multidrug Resistance — Perez-Jorge C, Gomez-Barrena E, Horcajada JP, Puig-Verdi L, Esteban J; Expert Opinion on Pharmacotherapy; 2016; 17:1233-1246; DOI: 10.1080/14656566.2016.1176142.