Clinical Scorecard: Successful Clinical and Microbiological Results in a War-Related Prosthetic Joint Infection Due to Klebsiella pneumoniae Treated with Combined Phage and Colistin Therapy

At a Glance

Key Highlights

• A 52-year-old man with war-related injuries developed a persistent prosthetic elbow infection caused by multidrug-resistant K. pneumoniae.

• After 4 weeks of intravenous antibiotics, he received a 14-week regimen of cefiderocol, fosfomycin, ertapenem, and colistin with repeated surgical debridement, but infection recurred.

• Personalized phage therapy was initiated with colistin after conventional antimicrobial therapy failed.

• The selected lytic phage demonstrated high activity against all 6 K. pneumoniae isolates obtained from the patient.

• No adverse effects were reported, and laboratory findings supported good tolerability of the combined treatment.

Guideline-Based Recommendations

Diagnosis

• Microbiological cultures were used to identify K. pneumoniae as the causative organism and to document recurrence and subsequent clearance.

• The patient isolates underwent capsular typing and phage-susceptibility testing to identify a lytic phage active against the infecting strain.

Management

• This case did not establish a formal guideline recommendation for phage therapy. The authors describe personalized phage therapy as a potential adjunctive option for complex multidrug-resistant infections when conventional therapies fail.

• In this patient, phage therapy was administered with colistin and surgical debridement as an alternative to more drastic intervention, including limb amputation.

Monitoring & Follow-up

• Clinical and laboratory monitoring included wound status, elbow mobility, C-reactive protein, glomerular filtration rate, white blood cell count, microbiological cultures, scintigraphy, and PET-CT.

• Microbiological monitoring showed undetectable K. pneumoniae by day 8, consecutive negative cultures on days 12 and 15, and continued negative routine cultures thereafter.

Risks

• Colistin carries significant toxicity risks, and colistin-associated nephrotoxicity had previously required treatment interruption in this patient.

• Neutralizing anti-phage antibodies developed during therapy, although their in vivo effect on treatment efficacy remained uncertain.

Patient & Prescribing Data

The patient was a 52-year-old man with extensive war-related orthopedic injuries who underwent total elbow arthroplasty and developed a prosthetic joint infection caused by multidrug-resistant K. pneumoniae.

Phage doses of 1.25 × 10^8 plaque-forming units were administered locally and intravenously with colistin at 2 MU every 8 hours. Local phage treatment was given once daily for the first 5 days, while twice-daily intravenous phage therapy continued for a total of 56 days.

Clinical Best Practices

• Complex prosthetic joint infections caused by multidrug-resistant organisms may require multidisciplinary management involving antimicrobial therapy and surgical intervention.

• Therapeutic phage preparations should undergo rigorous quality-control testing for sterility, pyrogenicity, and endotoxin content before clinical administration.

• The authors emphasize that personalized phage therapy remains an adjunctive strategy requiring further evaluation in well-designed clinical trials before routine implementation.

Related Resources & Content

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

• 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.

• 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.

• 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.