TY - JOUR
T1 - A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy
T2 - Production, Characteristics, and Clinical Outcomes
AU - Green, Sabrina I.
AU - Clark, Justin R.
AU - Santos, Haroldo H.
AU - Weesner, Kyle E.
AU - Salazar, Keiko C.
AU - Aslam, Saima
AU - Campbell, J. William
AU - Doernberg, Sarah B.
AU - Blodget, Emily
AU - Morris, Michele I.
AU - Suh, Gina A.
AU - Obeid, Karam
AU - Silveira, Fernanda P.
AU - Filippov, Andrey A.
AU - Whiteson, Katrine L.
AU - Trautner, Barbara W.
AU - Terwilliger, Austen L.
AU - Maresso, Anthony
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved.
PY - 2023/10/15
Y1 - 2023/10/15
N2 - 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.
AB - 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.
KW - antibiotic resistance
KW - microbiology
KW - phage
KW - phage therapy
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U2 - 10.1093/cid/ciad335
DO - 10.1093/cid/ciad335
M3 - Article
C2 - 37279523
AN - SCOPUS:85172401413
SN - 1058-4838
VL - 77
SP - 1079
EP - 1091
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 8
ER -