| Autor: |
Green, Sabrina I, Clark, Justin R, Santos, Haroldo H, Weesner, Kyle E, Salazar, Keiko C, Aslam, Saima, Campbell, J William, Doernberg, Sarah B, Blodget, Emily, Morris, Michele I, Suh, Gina A, Obeid, Karam, Silveira, Fernanda P, Filippov, Andrey A, Whiteson, Katrine L, Trautner, Barbara W, Terwilliger, Austen L, Maresso, Anthony |
| Předmět: |
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| Zdroj: |
Clinical Infectious Diseases; 10/15/2023, Vol. 77 Issue 8, p1079-1091, 13p |
| Abstrakt: |
Background Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections. Methods We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration–approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded. Results Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported. Conclusions Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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