Australian doctors have tested* a combination of bacteriophages and antibiotics in the treatment of infective endocarditis of a prosthetic valve. This marks the first time Western scientific literature has described the intravenous administration of a phage preparation for this disease.

A 65-year-old man who had a mechanical aortic valve implanted 30 years earlier presented to a medical facility with complaints of malaise, shortness of breath, and severe chest pain that worsened with deep breathing. Eight years prior, he had successfully completed antibiotic treatment for infective endocarditis of the prosthetic valve caused by Haemophilus aphrophilus . Examination revealed fever, tachypnea, tachycardia, hypotension (90-100 mmHg), and a systolic click. At this stage, no cardiac, renal, or hepatic failure or peripheral embolic complications of endocarditis (hematuria, hemorrhages) were observed. Blood cultures were consistent with methicillin-susceptible Staphylococcus aureus infection, determined by whole genome analysis, and the patient received high doses of flucloxacillin, ciprofloxacin, and rifampin.

Transesophageal echocardiography confirmed bacterial growth on the prosthetic aortic and native mitral valves and revealed thickening of the aortic root due to a possible perivalvular abscess. Establishment of extrapulmonary bypass was delayed due to a hemorrhagic infarction of the left anterior cerebral artery, which occurred seven days before the start of phage therapy.

Infective endocarditis caused by S. aureus is known to be associated with high mortality even with optimal antibiotic therapy. Therefore, a decision was made to add bacteriophages to the antimicrobial therapy regimen. An antistaphylococcal phage preparation was administered intravenously, beginning 9 days after the first positive bacteriological test, twice daily for 14 days, along with all previously prescribed antibiotics. We used AB-SA01, a preparation containing three types of lytic bacteriophages active against S. aureus . This phage preparation had recently been successfully used in the treatment of sinusitis (using local irrigation). The phage preparation was used in combination with a standard antibiotic regimen for severe staphylococcal infections.

Fig.1 . + = Pathogen present in blood; - = Pathogen absent in blood; CRP = C-reactive protein; SMA = superior mesenteric artery; WCC = white blood cells (Gilbey T et al., 2019).

By the start of phage therapy, the bacteria were no longer cultured from the blood. Within 24 hours of starting phage therapy, temperature, C-reactive protein, and leukocyte levels began to decline. This downward trend was interrupted only once due to splenic infarction and mesenteric artery occlusion in the patient. Overall, administration of the phage preparation was not accompanied by fever, tachycardia, hypotension, or pruritus.

The patient was discharged from the hospital after 40 days of antibiotic therapy. However, 58 days later, he developed progressive heart failure, refused surgery, and died.

The authors note that phage therapy for endocarditis was well tolerated, no side effects were observed, and it contributed to a reduction in the inflammatory process.

* Gilbey T, Ho J, Cooley LA et al. Adjunctive bacteriophage therapy for prosthetic valve endocarditis due to Staphylococcus aureus. Medical Journal of Australia, 2019, 211(3): 142-143.e1. https://doi.org/10.5694/mja2.50274