July 6,2022
Bacteriophage Therapies and Difficult-to-Treat Mycobacteria Infections By Brendan J. Kelly, MD, MS
Two recent reports present exciting evidence for the efficacy of bacteriophage therapies for difficult-to-treat mycobacteria infections.
In one of the articles, Jerry A. Nick and colleagues describe the intravenous (IV) administration of two mycobacteriophages to treat a case of Mycobacterium abscessus pulmonary infection that had failed to respond to appropriate antibiotic therapy in a patient with cystic fibrosis. The patient responded clinically to the addition of IV mycobacteriophages to antibiotic therapy, and he was discharged 5 days after initiation of phage therapy. Though sputum mycobacterial cultures remained largely positive in the first 100 days after treatment, 90% were negative between day 100 and the patient’s lung transplantation on day 379. In contrast, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa colonization of the lower respiratory tract were unchanged. The explanted lungs were culture-positive for Pseudomonas in all lobes but negative by culture for M. abscessus.
Mycobacteriophage treatment did not increase observed M. abscessus antibiotic resistance and did not select for phage-resistant isolates. Host antibody profiles did demonstrate a gradual increase in serum-mediated neutralization of the therapeutic mycobacteriophages.
In the other article, Jessica S. Little and colleagues report a similar application of a single mycobacteriophage as adjunctive treatment for a case of refractory cutaneous, disseminated Mycobacterium chelonae infection in a patient on tofacitinib for seronegative arthritis. The patient required prolonged treatment with trimethoprim-sulfamethoxazole, omadacycline, and bedaquiline, as well as multiple surgical debridements of skin lesions. After two weeks of twice daily intravenous mycobacteriophage administration, the patient had significant improvement in skin nodules; repeat biopsies performed approximately 2 and 5 months after initiation of therapy were negative for granulomas and for acid-fast bacilli.
As in the first report, an IgG-mediated immune response developed over the course of phage therapy; mildly neutralizing antibodies were observed after 17 days and potently neutralizing antibodies at 16 weeks. The patient has been continued on bacteriophage therapy, as well as antibiotic therapy, and has maintained a good clinical response despite ongoing immunosuppression.
These reports add to a growing body of evidence that bacteriophage therapy can be an important adjunct to antibiotics in cases of multidrug-resistant and refractory infections.
