Randomized Controlled Study on the Safety and Efficacy of Phage Cocktail in the Treatment of Multidrug-Resistant Bacterial Skin Infections

Summary

This study addresses the increasingly severe global public health challenge of antibiotic resistance, focusing on exploring phage therapy as a potential treatment strategy for multidrug-resistant bacterial skin infections. Bacteriophages, with advantages such as high specificity, low propensity for inducing resistance, and minimal side effects, have shown promise in preliminary clinical research for scenarios like chronic wound infections, demonstrating potential in reducing bacterial load and promoting healing. To this end, the study is designed as a prospective, double-blind, non-inferiority randomized controlled clinical trial, aiming to systematically evaluate the efficacy and safety of phage therapy compared to a placebo or standard treatment in patients with multidrug-resistant bacterial skin infections. The study plans to enroll patients aged 18 to 75 years, clinically diagnosed with a skin infection and with a wound area between 4 and 225 square centimeters. The infection must not involve deep tissue and should be suitable for topical treatment. All enrolled cases must have pathogenic bacteria detected in secretions or wound samples, and these bacteria must be resistant to key antibiotics (such as carbapenems) or show poor response to antibiotic therapy despite \*in vitro\* sensitivity. Patients who have received systemic antibacterial treatment within 72 hours before enrollment with no significant improvement may also be included. Participants of childbearing potential must agree to use effective contraception during the study and voluntarily provide written informed consent. Exclusion criteria primarily include: infections that can be effectively controlled by existing antimicrobials, or pathogens that are insensitive to the phage cocktail used in the study; pregnant or lactating women; patients whose infection symptoms have improved after using antimicrobials within 72 hours before enrollment; those receiving long-term or high-dose corticosteroids, immunosuppressants, chemotherapy, or other treatments that may interfere with the results; participation in other antimicrobial-related clinical trials within the past month; presence of severe wound infections (e.g., necrotizing fasciitis), chronic inflammatory skin diseases, multiple limb ulcers, non-removable implants, or gangrene; anticipated need for amputation surgery; history of clear allergic diseases, immune deficiency (including HIV positivity), mental disorders, or epilepsy; and any other condition deemed by the investigator as unsuitable for participation. These strict inclusion and exclusion criteria aim to select an appropriate target population, ensuring the scientific rigor and credibility of the study results.

Timeline

Start

2025-01-15

Primary completion

2027-10-31

Completion

2028-05

Publications

• Background GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. Lancet. 2024 Sep 28;404(10459):1199-1226. doi: 10.1016/S0140-6736(24)01867-1. Epub 2024 Sep 16.
• Background Green SI, Clark JR, Santos HH, Weesner KE, Salazar KC, Aslam S, Campbell JW, Doernberg SB, Blodget E, Morris MI, Suh GA, Obeid K, Silveira FP, Filippov AA, Whiteson KL, Trautner BW, Terwilliger AL, Maresso A. A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes. Clin Infect Dis. 2023 Oct 13;77(8):1079-1091. doi: 10.1093/cid/ciad335.
• Background Khatami A, Lin RCY, Petrovic-Fabijan A, Alkalay-Oren S, Almuzam S, Britton PN, Brownstein MJ, Dao Q, Fackler J, Hazan R, Horne B, Nir-Paz R, Iredell JR. Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child. EMBO Mol Med. 2021 Sep 7;13(9):e13936. doi: 10.15252/emmm.202113936. Epub 2021 Aug 9.
• Background Ding X, Tang Q, Xu Z, Xu Y, Zhang H, Zheng D, Wang S, Tan Q, Maitz J, Maitz PK, Yin S, Wang Y, Chen J. Challenges and innovations in treating chronic and acute wound infections: from basic science to clinical practice. Burns Trauma. 2022 May 21;10:tkac014. doi: 10.1093/burnst/tkac014. eCollection 2022.
• Background Kohler T, Luscher A, Falconnet L, Resch G, McBride R, Mai QA, Simonin JL, Chanson M, Maco B, Galiotto R, Riat A, Civic N, Docquier M, McCallin S, Chan B, van Delden C. Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa. Nat Commun. 2023 Jun 27;14(1):3629. doi: 10.1038/s41467-023-39370-z.
• Background Dedrick RM, Freeman KG, Nguyen JA, Bahadirli-Talbott A, Smith BE, Wu AE, Ong AS, Lin CT, Ruppel LC, Parrish NM, Hatfull GF, Cohen KA. Potent antibody-mediated neutralization limits bacteriophage treatment of a pulmonary Mycobacterium abscessus infection. Nat Med. 2021 Aug;27(8):1357-1361. doi: 10.1038/s41591-021-01403-9. Epub 2021 Jul 8.
• Background Pirnay JP, Djebara S, Steurs G, Griselain J, Cochez C, De Soir S, Glonti T, Spiessens A, Vanden Berghe E, Green S, Wagemans J, Lood C, Schrevens E, Chanishvili N, Kutateladze M, de Jode M, Ceyssens PJ, Draye JP, Verbeken G, De Vos D, Rose T, Onsea J, Van Nieuwenhuyse B; Bacteriophage Therapy Providers; Bacteriophage Donors; Soentjens P, Lavigne R, Merabishvili M. Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study. Nat Microbiol. 2024 Jun;9(6):1434-1453. doi: 10.1038/s41564-024-01705-x. Epub 2024 Jun 4.
• Background Liu M, Hernandez-Morales A, Clark J, Le T, Biswas B, Bishop-Lilly KA, Henry M, Quinones J, Voegtly LJ, Cer RZ, Hamilton T, Schooley RT, Salka S, Young R, Gill JJ. Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy. Nat Commun. 2022 Jun 30;13(1):3776. doi: 10.1038/s41467-022-31455-5.
• Background Sulakvelidze A, Alavidze Z, Morris JG Jr. Bacteriophage therapy. Antimicrob Agents Chemother. 2001 Mar;45(3):649-59. doi: 10.1128/AAC.45.3.649-659.2001. No abstract available.
• Background Mu A, McDonald D, Jarmusch AK, Martino C, Brennan C, Bryant M, Humphrey GC, Toronczak J, Schwartz T, Nguyen D, Ackermann G, D'Onofrio A, Strathdee SA, Schooley RT, Dorrestein PC, Knight R, Aslam S. Assessment of the microbiome during bacteriophage therapy in combination with systemic antibiotics to treat a case of staphylococcal device infection. Microbiome. 2021 Apr 14;9(1):92. doi: 10.1186/s40168-021-01026-9.
• Background Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, Segall AM, Taplitz R, Smith DM, Kerr K, Kumaraswamy M, Nizet V, Lin L, McCauley MD, Strathdee SA, Benson CA, Pope RK, Leroux BM, Picel AC, Mateczun AJ, Cilwa KE, Regeimbal JM, Estrella LA, Wolfe DM, Henry MS, Quinones J, Salka S, Bishop-Lilly KA, Young R, Hamilton T. Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection. Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00954-17. doi: 10.1128/AAC.00954-17. Print 2017 Oct.
• Results Chan BK, Stanley GL, Kortright KE, Vill AC, Modak M, Ott IM, Sun Y, Wurstle S, Grun CN, Kazmierczak BI, Rajagopalan G, Harris ZM, Britto CJ, Stewart J, Talwalkar JS, Appell CR, Chaudary N, Jagpal SK, Jain R, Kanu A, Quon BS, Reynolds JM, Teneback CC, Mai QA, Shabanova V, Turner PE, Koff JL. Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis. Nat Med. 2025 May;31(5):1494-1501. doi: 10.1038/s41591-025-03678-8. Epub 2025 Apr 29.

Drugs

Indications

No indication recorded.