A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes

被引：40

作者：

Green, Sabrina, I ^{[1
,2
]}

Clark, Justin R. ^{[1
]}

Santos, Haroldo H. ^{[1
]}

Weesner, Kyle E. ^{[1
]}

Salazar, Keiko C. ^{[1
]}

Aslam, Saima ^{[3
]}

Campbell, J. William ^{[4
]}

Doernberg, Sarah B. ^{[5
]}

Blodget, Emily ^{[6
]}

Morris, Michele, I ^{[7
]}

Suh, Gina A. ^{[8
]}

Obeid, Karam ^{[9
]}

Silveira, Fernanda P. ^{[10
]}

Filippov, Andrey A. ^{[11
]}

Whiteson, Katrine L. ^{[12
]}

Trautner, Barbara W. ^{[13
,14
]}

Terwilliger, Austen L. ^{[1
]}

Maresso, Anthony ^{[1
]}

机构：

[1] Baylor Coll Med, Dept Mol Virol & Microbiol, Tailored Antibacterials & Innovat Labs Phage Res, Houston, TX USA

[2] Katholieke Univ Leuven, Lab Gene Technol, Leuven, Belgium

[3] Univ Calif San Diego, Ctr Innovat Phage Applicat & Therapeut, Div Infect Dis & Global Publ Hlth, La Jolla, CA USA

[4] St Lukes Hosp, Div Infect Dis & Infect Prevent, Chesterfield, MO USA

[5] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA

[6] Univ Calif Irvine, Dept Med, Irvine, CA USA

[7] Univ Miami, Miller Sch Med, Dept Med, Div Infect Dis, Miami, FL USA

[8] Mayo Clin, Dept Med, Div Infect Dis, Rochester, MN USA

[9] Univ Minnesota, Div Infect Dis & Int Med, Dept Med, Minneapolis, MN USA

[10] Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA USA

[11] Walter Reed Army Inst Res, Wound Infect Dept, Bacterial Dis Branch, Silver Spring, MD USA

[12] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA USA

[13] Michael E DeBakey VA Med Ctr, Dept Med, Houston, TX USA

[14] Baylor Coll Med, Dept Med, Houston, TX USA

来源：

CLINICAL INFECTIOUS DISEASES | 2023年 / 77卷 / 08期

基金：

美国国家卫生研究院;

关键词：

antibiotic resistance; phage; phage therapy; microbiology;

D O I：

10.1093/cid/ciad335

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. Antimicrobial resistant infections present clinical challenges. Here, we report the experiences and outcomes of a dedicated phage discovery, manufacturing, and characterization platform for customized phage therapy for a range of heterogenous and complex resistant bacterial infections.

引用

页码：1079 / 1091

页数：13

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