Current State of Compassionate Phage Therapy.

Shawna McCallin, Jessica C Sacher, Jan Zheng, Benjamin K Chan
Author Information
  1. Shawna McCallin: Unit of Regenerative Medicine, Department of Musculoskeletal Medicine, Service of Plastic, Reconstructive, & Hand Surgery, University Hospital of Lausanne (CHUV), 1066 Epalignes, Switzerland. Shawna.mccallin@gmail.com.
  2. Jessica C Sacher: Phage Directory, Atlanta, GA 30303, USA. jessica@phage.directory.
  3. Jan Zheng: Phage Directory, Atlanta, GA 30303, USA. jan@phage.directory.
  4. Benjamin K Chan: Yale University New Haven, CT 06520, USA. b.chan@yale.edu.

Abstract

There is a current unmet medical need for the treatment of antibiotic-resistant infections, and in the absence of approved alternatives, some clinicians are turning to empirical ones, such as phage therapy, for compassionate treatment. Phage therapy is ideal for compassionate use due to its long-standing historical use and publications, apparent lack of adverse effects, and solid support by fundamental research. Increased media coverage and peer-reviewed articles have given rise to a more widespread familiarity with its therapeutic potential. However, compassionate phage therapy (cPT) remains limited to a small number of experimental treatment centers or associated with individual physicians and researchers. It is possible, with the creation of guidelines and a greater central coordination, that cPT could reach more of those in need, starting by increasing the availability of phages. Subsequent steps, particularly production and purification, are difficult to scale, and treatment paradigms stand highly variable between cases, or are frequently not reported. This article serves both to synopsize cPT publications to date and to discuss currently available phage sources for cPT. As the antibiotic resistance crisis continues to grow and the future of phage therapy clinical trials remains undetermined, cPT represents a possibility for bridging the gap between current treatment failures and future approved alternatives. Streamlining the process of cPT will help to ensure high quality, therapeutically-beneficial, and safe treatment.

Keywords

References

  1. Clin Exp Dermatol. 2005 Jan;30(1):23-6 [PMID: 15663496]
  2. Folia Microbiol (Praha). 2009 Sep;54(5):457-61 [PMID: 19937220]
  3. Lancet. 2005 Jun 25-Jul 1;365(9478):2166-7 [PMID: 15986542]
  4. Methods Mol Biol. 2018;1693:159-170 [PMID: 29119440]
  5. Open Forum Infect Dis. 2018 Mar 23;5(4):ofy064 [PMID: 29687015]
  6. Trends Microbiol. 2015 Apr;23(4):185-91 [PMID: 25708933]
  7. Clin Infect Dis. 2019 Nov 13;69(11):2015-2018 [PMID: 30869755]
  8. Folia Microbiol (Praha). 2006;51(3):236-8 [PMID: 17004656]
  9. Aust Prescr. 2017 Oct;40(5):194-196 [PMID: 29109604]
  10. EBioMedicine. 2016 Jan 05;4:124-37 [PMID: 26981577]
  11. Res Microbiol. 2018 Nov;169(9):540-542 [PMID: 29777836]
  12. Evol Med Public Health. 2018 Mar 08;2018(1):60-66 [PMID: 29588855]
  13. Rev Infect Dis. 1987 Nov-Dec;9(6):1095-101 [PMID: 3321359]
  14. Open Forum Infect Dis. 2018 Oct 24;5(11):ofy269 [PMID: 30474047]
  15. J Pediatric Infect Dis Soc. 2018 Aug 17;7(3):253-256 [PMID: 28992111]
  16. World J Gastrointest Pharmacol Ther. 2017 Aug 6;8(3):162-173 [PMID: 28828194]
  17. J Med Microbiol. 2011 Nov;60(Pt 11):1697-1700 [PMID: 21737541]
  18. Bacteriophage. 2012 Apr 1;2(2):130-133 [PMID: 23050223]
  19. Crit Care. 2017 Jun 4;21(1):129 [PMID: 28583189]
  20. J Hist Med Allied Sci. 1993 Jul;48(3):275-301 [PMID: 8409365]
  21. Cell Host Microbe. 2019 Feb 13;25(2):219-232 [PMID: 30763536]
  22. Can J Infect Dis Med Microbiol. 2007 Jan;18(1):19-26 [PMID: 18923687]
  23. N Engl J Med. 2018 Feb 22;378(8):695-697 [PMID: 29320302]
  24. Front Microbiol. 2018 Aug 07;9:1832 [PMID: 30131795]
  25. Nature. 2014 Jun 5;510(7503):15-6 [PMID: 24899282]
  26. Antibiotics (Basel). 2018 Oct 02;7(4): [PMID: 30279396]
  27. Virol Sin. 2015 Feb;30(1):80-1 [PMID: 25662889]
  28. Open Ophthalmol J. 2015 Nov 04;9:167-8 [PMID: 26862360]
  29. Int J Dermatol. 2002 Jul;41(7):453-8 [PMID: 12121566]
  30. Front Microbiol. 2016 Aug 12;7:1177 [PMID: 27570518]
  31. JAMA. 2013 Nov 27;310(20):2191-4 [PMID: 24141714]
  32. Front Microbiol. 2018 Aug 02;9:1696 [PMID: 30116226]
  33. Arch Immunol Ther Exp (Warsz). 2000;48(6):547-51 [PMID: 11197610]
  34. Intractable Rare Dis Res. 2016 Nov;5(4):244-254 [PMID: 27904819]
  35. BMC Med. 2017 Jul 24;15(1):136 [PMID: 28735571]
  36. Clin Otolaryngol. 2009 Aug;34(4):349-57 [PMID: 19673983]
  37. Lancet Infect Dis. 2019 Jan;19(1):56-66 [PMID: 30409683]
  38. Transplant Proc. 2003 Jun;35(4):1385-6 [PMID: 12826166]
  39. BMC Med. 2016 Feb 02;14:17 [PMID: 26843367]
  40. J Pharm Policy Pract. 2017 Feb 21;10:10 [PMID: 28239479]
  41. Int J Burns Trauma. 2014 Oct 26;4(2):66-73 [PMID: 25356373]
  42. Br J Clin Pharmacol. 2004 Jun;57(6):695-713 [PMID: 15151515]
  43. J Antimicrob Chemother. 2018 Oct 1;73(10):2901-2903 [PMID: 30060002]
  44. Antimicrob Agents Chemother. 2017 Sep 22;61(10): [PMID: 28807909]
  45. Viruses. 2018 Dec 28;11(1): [PMID: 30597868]
  46. Clin Transl Sci. 2015 Oct;8(5):526-32 [PMID: 25588691]
  47. Viruses. 2018 Feb 06;10(2): [PMID: 29415431]
  48. Ther Innov Regul Sci. 2017 Mar 1;51(2):177-179 [PMID: 28553565]
  49. Emerg Top Life Sci. 2017 Apr 21;1(1):105-116 [PMID: 33525819]
  50. Pharmaceuticals (Basel). 2017 Apr 30;10(2): [PMID: 28468287]
  51. Lancet Infect Dis. 2019 Jan;19(1):35-45 [PMID: 30292481]
  52. Front Med (Lausanne). 2017 Jul 03;4:94 [PMID: 28717637]
  53. Burns. 2006 Aug;32(5):644-6 [PMID: 16781080]
  54. Adv Virus Res. 2012;83:73-121 [PMID: 22748809]
  55. Antimicrob Agents Chemother. 2001 Mar;45(3):649-59 [PMID: 11181338]
  56. Bull N Y Acad Med. 1931 May;7(5):329-48 [PMID: 19311785]

Grants

  1. UL1 TR001863/NCATS NIH HHS

MeSH Term

Bacterial Infections
Compassionate Use Trials
Drug Resistance, Multiple, Bacterial
Humans
Phage Therapy

Word Cloud

Created with Highcharts 10.0.0treatmentcPTtherapyphagecompassionateusecurrentneedapprovedalternativesPhagepublicationsremainsantibioticresistancefutureunmetmedicalantibiotic-resistantinfectionsabsencecliniciansturningempiricalonesidealduelong-standinghistoricalapparentlackadverseeffectssolidsupportfundamentalresearchIncreasedmediacoveragepeer-reviewedarticlesgivenrisewidespreadfamiliaritytherapeuticpotentialHoweverlimitedsmallnumberexperimentalcentersassociatedindividualphysiciansresearcherspossiblecreationguidelinesgreatercentralcoordinationreachstartingincreasingavailabilityphagesSubsequentstepsparticularlyproductionpurificationdifficultscaleparadigmsstandhighlyvariablecasesfrequentlyreportedarticleservessynopsizedatediscusscurrentlyavailablesourcescrisiscontinuesgrowclinicaltrialsundeterminedrepresentspossibilitybridginggapfailuresStreamliningprocesswillhelpensurehighqualitytherapeutically-beneficialsafeCurrentStateCompassionateTherapybacteriophage

Similar Articles

Cited By