Abstract
Antibiotic resistance is a worsening global problem, and phage therapy can be an option for some patients when antibiotics fail. While not approved as a medicine in most of the world, especially in countries that practice Western medicine, phage therapy is being increasingly practiced on a compassionate basis in countries where it has not previously been widely done. Due to the complexity of treating patients with phages, especially in the absence of extensive phage therapy experience, multidisciplinary collaborations and new systems are helping to address current gaps to make compassionate phage therapy possible for more patients around the world. This chapter provides an overview of the general process of treating multidrug-resistant bacterial infections with compassionate phage therapy, with a focus on how it has been done in regions without established phage therapy infrastructure, especially within the last 3 years. We provide several recent examples of compassionate phage therapy that depict both the challenges and how collaborations have led to solutions. Lastly, we provide examples of new systems and organizations that have been created to facilitate compassionate phage therapy, with an emphasis on the online platform Phage Directory.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Abedon ST (2017) Information phage therapy research should report. Pharmaceuticals. https://doi.org/10.3390/ph10020043
Adaptive Phage Therapeutics (2019a) Compassionate use case studies. http://www.aphage.com/compassionate-use-case-studies/. Accessed 2 Jun 2019
Adaptive Phage Therapeutics (2019b) Adaptive phage therapeutics enters into collaboration agreement with researchers at Yale University to manufacture and supply therapeutic bacteriophage. https://www.businesswire.com/news/home/20181212005601/en/Adaptive-Phage-Therapeutics-Enters-Collaboration-Agreement-Researchers. Accessed 2 Jun 2019
Aslam S, Pretorius V, Lehman SM et al (2019) Novel bacteriophage therapy for treatment of left ventricular assist device infection. J Heart Lung Transplant 38(4):475–476
Balasubramanian G, Morampudi S, Chhabra P et al (2016) An overview of compassionate use programs in the European union member states. Intractable Rare Dis Res 5(4):244–254
Bonilla N, Rojas MI, Netto Flores Cruz G et al (2016) Phage on tap–a quick and efficient protocol for the preparation of bacteriophage laboratory stocks. PeerJ. https://doi.org/10.7717/peerj.2261
Center for Innovative Phage Applications and Therapeutics (2019) Center for innovative phage applications and therapeutics. https://ipath.ucsd.edu. Accessed 2 Jun 2019
Chan BK, Turner PE, Kim S et al (2018) Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol Med Public Heal. https://doi.org/10.1093/emph/eoy005
Debarbieux L, Pirnay JP, Verbeken G et al (2016) A bacteriophage journey at the European Medicines agency. FEMS Microbiol Lett 363(2). https://doi.org/10.1093/femsle/fnv225
Dedrick RM, Guerrero-Bustamante CA, Garlena RA et al (2019) Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat Med. https://doi.org/10.1038/s41591-019-0437-z
Djebara S, Maussen C, De Vos D et al (2019) Processing phage therapy requests in a Brussels Military Hospital: lessons identified. Viruses 11:265. https://doi.org/10.3390/v11030265
Donovan P (2017) Access to unregistered drugs in Australia. Aust Prescr. https://doi.org/10.18773/austprescr.2017.062
Duplessis C, Biswas B, Hanisch B et al (2018) Refractory pseudomonas bacteremia in a 2-year-old sterilized by bacteriophage therapy. J Pediatric Infect Dis Soc. https://doi.org/10.1093/jpids/pix056
Eliava Phage Therapy Center (2019) Partners. https://eliavaphagetherapy.com/partners/. Accessed 2 Jun 2019
Emily’s Entourage (2019) Emily’s entourage awards over $400,000 to Cystic Fibrosis Research. https://www.emilysentourage.org/ee-awards-over-400000-to-cystic-fibrosis-research/. Accessed 2 Jun 2019
European Medicines Agency (2019) Compassionate use. https://www.ema.europa.eu/en/human-regulatory/research-development/compassionate-use. Accessed 2 Jun 2019
Fabijan AP, Lin RC, Ho J et al (2019) Safety and tolerability of bacteriophage therapy in severe staphylococcus aureus infection. bioRxiv. https://doi.org/10.1101/619999
Fadlallah A, Chelala E, Legeais J-M (2015) Corneal infection therapy with topical bacteriophage administration. Open Ophthalmol J. https://doi.org/10.2174/1874364101509010167
Ferry T, Boucher F, Fevre C et al (2018a) Innovations for the treatment of a complex bone and joint infection due to XDR Pseudomonas aeruginosa including local application of a selected cocktail of bacteriophages. J Antimicrob Chemother 73(10):2901–2903
Ferry T, Leboucher G, Fevre C et al (2018b) Salvage ‘DAIR’ (debridement, antibiotics and implant retention) with local injection of a selected cocktail of bacteriophages: is it an option for an elderly patient with relapsing S. aureus prosthetic-joint infection? Open Forum Infect Dis. https://doi.org/10.1093/ofid/ofy269
Fish R, Kutter E, Wheat G et al (2016) Bacteriophage treatment of intransigent diabetic toe ulcers: a case series. J Wound Care. https://doi.org/10.12968/jowc.2016.25.7s27
Fish R, Kutter E, Wheat G et al (2018) Compassionate use of bacteriophage therapy for foot ulcer treatment as an effective step for moving toward clinical trials. In: Methods in molecular biology. Humana Press, Clifton
Henry M, Biswas B, Vincent L et al (2012) Development of a high throughput assay for indirectly measuring phage growth using the OmniLog TM system. Bacteriophage. https://doi.org/10.4161/bact.21440
Hoyle N, Zhvaniya P, Balarjishvili N et al (2018) Phage therapy against Achromobacter xylosoxidans lung infection in a patient with cystic fibrosis: a case report. Res Microbiol. https://doi.org/10.1016/j.resmic.2018.05.001
Jarow JP, Lurie P, Ikenberry SC, Lemery S (2017) Overview of FDA’s expanded access program for investigational drugs. Ther Innov Regul Sci. https://doi.org/10.1177/2168479017694850
Jennes S, Merabishvili M, Soentjens P et al (2017) Use of bacteriophages in the treatment of colistin-only-sensitive Pseudomonas aeruginosa septicaemia in a patient with acute kidney injury—a case report. Crit Care. https://doi.org/10.1186/s13054-017-1709-y
Jikia D, Chkhaidze N, Imedashvili E et al (2005) The use of a novel biodegradable preparation capable of the sustained release of bacteriophages and ciprofloxacin, in the complex treatment of multidrug-resistant Staphylococcus aureus-infected local radiation injuries caused by exposure to Sr90. Clin Exp Dermatol. https://doi.org/10.1111/j.1365-2230.2004.01600.x
Khawaldeh A, Morales S, Dillon B et al (2011) Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection. J Med Microbiol. https://doi.org/10.1099/jmm.0.029744-0
Kortright KE, Chan BK, Koff JL, Turner PE (2019) Phage therapy: a renewed approach to combat antibiotic-resistant bacteria. Cell Host Microbe 25(2):219–232
Kutter E, De Vos D, Gvasalia G et al (2010) Phage therapy in clinical practice: treatment of human infections. Curr Pharm Biotechnol. https://doi.org/10.2174/138920110790725401
Kutter EM, Kuhl SJ, Abedon ST (2015) Re-establishing a place for phage therapy in western medicine. Future Microbiol. https://doi.org/10.2217/fmb.15.28
LaFee S, Buschman H (2019) With OK from FDA, UC San Diego Researchers Prepare to Launch Novel Phage Study. https://health.ucsd.edu/news/releases/Pages/2019-01-08-FDA-okays-uc-san-diego-to-launch-novel-phage-study.aspx. Accessed 2 Jun 2019
LaVergne S, Hamilton T, Biswas B et al (2018) Phage therapy for a multidrug-resistant Acinetobacter baumannii Craniectomy site infection. Open Forum Infect Dis. https://doi.org/10.1093/ofid/ofy064
Leszczyński P, Weber-Da̧browska B, Kohutnicka M et al (2006) Successful eradication of methicillin-resistant Staphylococcus aureus (MRSA) intestinal carrier status in a healthcare worker – case report. Folia Microbiol (Praha). https://doi.org/10.1007/BF02932128
Letkiewicz S, Miedzybrodzki R, Fortuna W et al (2009) Eradication of enterococcus faecalis by phage therapy in chronic bacterial prostatitis – case report. Folia Microbiol (Praha). https://doi.org/10.1007/s12223-009-0064-z
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy (2019) Phage therapy unit. https://www.iitd.pan.wroc.pl/en/OTF/index.html. Accessed 3 Jun 2019
Markoishvili K, Tsitlanadze G, Katsarava R et al (2002) A novel sustained-release matrix based on biodegradable polyester amides and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds. Int J Dermatol 41:453–458
Marza JAS, Soothill JS, Boydell P, Collyns TA (2006) Multiplication of therapeutically administered bacteriophages in Pseudomonas aeruginosa infected patients. Burns. https://doi.org/10.1016/j.burns.2006.02.012
McCallin S, Sacher JC, Zheng J, Chan BK (2019) Current state of compassionate phage therapy. Viruses 11(4):343
Międzybrodzki R, Borysowski J, Weber-Dabrowska B et al (2012) Clinical aspects of phage therapy. In: Advances in virus research
Morozova VV, Vlassov VV, Tikunova NV (2018) Applications of bacteriophages in the treatment of localized infections in humans. Front Microbiol 9, 1696. https://doi.org/10.1016/10.3389/fmicb.2018.01696
Nir-Paz R, Gelman D, Khouri A et al (2019) Successful treatment of antibiotic-resistant, poly-microbial bone infection with bacteriophages and antibiotics combination. Clin Infect Dis. https://doi.org/10.1093/cid/ciz222
O’Neill J (2014) Antimicrobial resistance: tackling a crisis for the health and wealth of nations. Rev Antimicrob Resist. https://doi.org/10.1038/510015a
Patey O, McCallin S, Mazure H et al (2019) Clinical indications and compassionate use of phage therapy: personal experience and literature review with a focus on osteoarticular infections. Viruses 11. https://doi.org/10.3390/v11010018
Phage Directory (2019a) Phage directory. https://phage.directory. Accessed 2 Jun 2019
Phage Directory (2019b) Alerts. https://phage.directory/alerts. Accessed 2 Jun 2019
Phage Directory (2019c) Capsid and tail. https://phage.directory/capsid. Accessed 2 Jun 2019
Pirnay JP, Verbeken G, Ceyssens PJ et al (2018) The magistral phage. Viruses 10. https://doi.org/10.3390/v10020064
Rose T, Verbeken G, De VD et al (2014) Experimental phage therapy of burn wound infection: difficult first steps. Int J Burn Trauma 4:66–73
Sacher JC (2019) Improving access to phage therapy in India. In: Capsid tail. https://phage.directory/capsid/phage-therapy-access-india. Accessed 2 Jun 2019
Sacher JC, Zheng J, McCallin S (2019) Sourcing phages for compassionate use. Microbiol Aust. https://doi.org/10.1071/MA19012
Schooley RT, Biswas B, Gill JJ et al (2017) Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.00954-17
Servick K (2018) U.S. center will fight infections with viruses. Science 80. https://doi.org/10.1126/science.360.6395.1280
Smith M (2019) Salt in my soul: an unfinished life. Penguin Random House, New York
Strathdee S, Patterson T (2019) The perfect predator: a Scientist’s race to save her husband from a deadly superbug: a memoir. Hachette Book Group, New York
Ujmajuridze A, Chanishvili N, Goderdzishvili M et al (2018) Adapted bacteriophages for treating urinary tract infections. Front Microbiol. https://doi.org/10.3389/fmicb.2018.01832
US Food and Drug Administration (2019) Expanded access. https://www.fda.gov/news-events/public-health-focus/expanded-access. Accessed 2 Jun 2019
Vitalis Phage Therapy (2019) Vitalis phage therapy. https://www.vitalisphagetherapy.com. Accessed 30 May 2019
Weber-Dabrowska B, Mulczyk M, Görski A (2001) Bacteriophage therapy for infections in cancer patients. Clin Appl Immunol Rev 1(3–4):131–134
Weber-Dąbrowska B, Mulczyk M, Górski A (2001) Bacteriophage therapy of bacterial infections: an update of our Institute’s experience. In: Inflammation
Weber-Da̧browska B, Mulczyk M, Górski A (2003) Bacteriophages as an efficient therapy for antibiotic-resistant septicemia in man. Transplant Proc. https://doi.org/10.1016/S0041-1345(03)00525-6
Weber-Dabrowska B, Jończyk-Matysiak E, Zaczek M et al (2016) Bacteriophage procurement for therapeutic purposes. Front Microbiol
World Medical Association (2013) World medical association declaration of Helsinki. JAMA 310:2191. https://doi.org/10.1001/jama.2013.281053
Zhvania P, Hoyle NS, Nadareishvili L et al (2017) Phage therapy in a 16-year-old boy with Netherton syndrome. Front Med. https://doi.org/10.3389/fmed.2017.00094
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this entry
Cite this entry
Sacher, J.C., Zheng, J. (2021). Phage Therapy Collaboration and Compassionate Use. In: Harper, D.R., Abedon, S.T., Burrowes, B.H., McConville, M.L. (eds) Bacteriophages. Springer, Cham. https://doi.org/10.1007/978-3-319-41986-2_50
Download citation
DOI: https://doi.org/10.1007/978-3-319-41986-2_50
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-41985-5
Online ISBN: 978-3-319-41986-2
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences