Doctors from the Giorgi Eliava Phage Therapy Center (Tbilisi, Georgia) published an article* describing four clinical cases of phage therapy for surgical wounds. We present one of them: the treatment of chronic osteomyelitis.

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The patient, a 60-year-old woman , suffered from chronic osteomyelitis of the right tibia caused by a hospital-acquired strain of Staphylococcus aureus 30 years ago. The disease was accompanied by chronic pain. In 2005, a large fistula developed in the right tibia. One year later, the affected area developed necrosis, requiring surgical treatment. Bone cement with an antibiotic was used during the reconstructive procedure.

In August 2016, three ulcers developed on the affected leg, for which the patient sought treatment at the Georgiy Eliava Phage Therapy Center. At the time of her visit, the patient was suffering from intense pain, and her mobility was significantly limited.

The patient was diagnosed with type 2 diabetes in 2010. A blood test revealed elevated glycated hemoglobin levels (8.4%).

Physical examination : the skin on the affected leg is red, tender, and fragile. Purulent ulcers are clearly visible: one measures 2.5 x 1.5 cm, the other 0.5 x 0.5 cm (Fig. 1a, b).

Fig. 1. Phage therapy of chronic osteomyelitis: (a) (b) affected leg before phage therapy; (c) affected leg after phage therapy: skin condition improved, ulcers healed.

Microbiology : bacterial culture from wounds revealed a strain of S. aureus sensitive to most modern antibiotics.

Analysis of phage susceptibility of the S. aureus strain showed the activity of five commercial phage cocktails. For therapy, the following were selected: staphylococcal bacteriophage, phage cocktail Intestifag (contains bacteriophages specific against Shigella flexneri (Serotypes 1,2,3,4) Shigella sonnei; Shigella newcastle; Salmonella paratyphi A, Salmonella paratyphi B; Salmonella typhimurium; Salmonella enteritidis; Salmonella choleraesuis; Salmonella oranienburg; E. coli; Proteus vulgaris; Staphylococcus aureus; Pseudomonas aeruginosa; Enterococcus faecalis ), phage cocktail Pyophage [ Staphylococcus spp., Streptococcus (S. pyogenes, S. sanguis, S. salivarius, S. agalactiae), Escherichia coli, Pseudomonas aeruginosa, Proteus (mirabilis and vulgaris) ], as well as a phage cocktail SES-bacteriophage ( Staphylococcus spp., Streptococcus spp. and various types of enteropathogenic E. coli ).

Treatment

Staphylococcal bacteriophage and Intestifag were administered orally, and staphylococcal bacteriophage was also applied topically. Staphylococcal bacteriophage (10 ml once daily) was applied using a sterile syringe to a gauze pad, which was then applied to the wound under a sterile adhesive dressing.

The patient received phage preparations orally at doses of 10 ml once daily (before taking the phage preparation, 100 ml of alkaline mineral water was used as an antacid). The course of treatment lasted 20 days. After a 21-day break, a second course of phage therapy began, consisting of staphylococcal bacteriophage 10 ml once daily in the morning, pyobacteriophage 10 ml once daily in the afternoon, and SES bacteriophage 10 ml once daily in the evening for 15 days. During the second course of treatment, pyobacteriophage ointment was also applied to the ulcers twice daily for 15 days. The patient did not take antibiotics during the treatment period.

After a 21-day break, the third course of phage therapy was started: orally pyobacteriophage 10 ml 1 time/day in the morning and SES-bacteriophage 10 ml 1 time/day in the evening in combination with the use of ointment with Pyophage for 15 days.

After 1 year, despite satisfactory health and stable remission of osteomyelitis, the patient was prescribed a prophylactic course of oral phage preparations.

Results

Phage therapy resulted in improvement in the patient's condition. The wounds were visibly filled with new tissue, the fibropurulent layer cleared, and granulation tissue formed (Fig. 1c). Complete healing of the ulcers occurred by the 18th week of treatment. No recurrences of osteomyelitis were observed for two years following phage therapy.

The patient did not experience any allergic reactions or other side effects during treatment.

*Nadareishvili L., Hoyle N., Nakaidze N. et al. Bacteriophage Therapy as a Potential Management Option for Surgical Wound Infections. PHAGE: Therapy, Applications, and Research, 2020; 1 (3). DOI: 10.1089/phage.2020.0010