Experimental Phage Therapy of Burn Wound Infection: Difficult First Steps

Overview

Journal Int J Burns Trauma

Date 2014 Oct 31

PMID 25356373

Citations 108

Authors

Thomas Rose

Gilbert Verbeken

Daniel De Vos

Maya Merabishvili

Mario Vaneechoutte

Rob Lavigne

Serge Jennes

Martin Zizi

Jean-Paul Pirnay

Affiliations

Soon will be listed here.

Abstract

Antibiotic resistance has become a major public health problem and the antibiotics pipeline is running dry. Bacteriophages (phages) may offer an 'innovative' means of infection treatment, which can be combined or alternated with antibiotic therapy and may enhance our abilities to treat bacterial infections successfully. Today, in the Queen Astrid Military Hospital, phage therapy is increasingly considered as part of a salvage therapy for patients in therapeutic dead end, particularly those with multidrug resistant infections. We describe the application of a well-defined and quality controlled phage cocktail, active against Pseudomonas aeruginosa and Staphylococcus aureus, on colonized burn wounds within a modest clinical trial (nine patients, 10 applications), which was approved by a leading Belgian Medical Ethical Committee. No adverse events, clinical abnormalities or changes in laboratory test results that could be related to the application of phages were observed. Unfortunately, this very prudent 'clinical trial' did not allow for an adequate evaluation of the efficacy of the phage cocktail. Nevertheless, this first 'baby step' revealed several pitfalls and lessons for future experimental phage therapy and helped overcome the psychological hurdles that existed to the use of viruses in the treatment of patients in our burn unit.

Citing Articles

The Role of Active Packaging in the Defense Against Foodborne Pathogens with Particular Attention to Bacteriophages.

Wagh R, Priyadarshi R, Khan A, Riahi Z, Packialakshmi J, Kumar P Microorganisms. 2025; 13(2).

PMID: 40005767 PMC: 11858251. DOI: 10.3390/microorganisms13020401.

Phage Therapy for Orthopaedic Infections: The First Three Cases from the United Kingdom.

Munteanu D, Dunn J, Apjok G, Kintses B, Griselain J, Steurs G Antibiotics (Basel). 2025; 14(2).

PMID: 40001358 PMC: 11851713. DOI: 10.3390/antibiotics14020114.

Advancing Phage Therapy: A Comprehensive Review of the Safety, Efficacy, and Future Prospects for the Targeted Treatment of Bacterial Infections.

Palma M, Qi B Infect Dis Rep. 2024; 16(6):1127-1181.

PMID: 39728014 PMC: 11675988. DOI: 10.3390/idr16060092.

Phage therapeutic delivery methods and clinical trials for combating clinically relevant pathogens.

Selim H, Gomaa F, Alshahrani M, Morgan R, Aboshanab K Ther Deliv. 2024; 16(3):247-269.

PMID: 39545771 PMC: 11875505. DOI: 10.1080/20415990.2024.2426824.

Efficacy of Bacteriophages in Wound Healing: An Updated Review.

Narayanan M, Kumar A, Verma G, Bairwa A, Mirza A, Goyal B Cureus. 2024; 16(10):e71542.

PMID: 39544596 PMC: 11563050. DOI: 10.7759/cureus.71542.

References

Church D, Elsayed S, Reid O, Winston B, Lindsay R . Burn wound infections. Clin Microbiol Rev. 2006; 19(2):403-34. PMC: 1471990. DOI: 10.1128/CMR.19.2.403-434.2006. View

Pirnay J, De Vos D, Verbeken G, Merabishvili M, Chanishvili N, Vaneechoutte M . The phage therapy paradigm: prêt-à-porter or sur-mesure?. Pharm Res. 2010; 28(4):934-7. DOI: 10.1007/s11095-010-0313-5. View

Thiel K . Old dogma, new tricks--21st Century phage therapy. Nat Biotechnol. 2004; 22(1):31-6. DOI: 10.1038/nbt0104-31. View

Altoparlak U, Erol S, Akcay M, Celebi F, Kadanali A . The time-related changes of antimicrobial resistance patterns and predominant bacterial profiles of burn wounds and body flora of burned patients. Burns. 2004; 30(7):660-4. DOI: 10.1016/j.burns.2004.03.005. View

Weber-Dabrowska B, MULCZYK M, Gorski A . Bacteriophage therapy of bacterial infections: an update of our institute's experience. Arch Immunol Ther Exp (Warsz). 2001; 48(6):547-51. View

Manelli J, Palayret D, Carlin G, Echinard C, JOUGLARD J . [Evaluation of septicemia risk in burn patients. Parallel between skin bacterial count and blood culture]. Nouv Presse Med. 1976; 5(29):1831-2. View

Kutter E, De Vos D, Gvasalia G, Alavidze Z, Gogokhia L, Kuhl S . Phage therapy in clinical practice: treatment of human infections. Curr Pharm Biotechnol. 2010; 11(1):69-86. DOI: 10.2174/138920110790725401. View

Markoishvili K, Tsitlanadze G, Katsarava R, Morris Jr J, Sulakvelidze A . A novel sustained-release matrix based on biodegradable poly(ester amide)s and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds. Int J Dermatol. 2002; 41(7):453-8. DOI: 10.1046/j.1365-4362.2002.01451.x. View

Berg J, Mossner B, Skov M, Lauridsen J, Gottrup F, Kolmos H . Antibacterial properties of EMLA and lidocaine in wound tissue biopsies for culturing. Wound Repair Regen. 2006; 14(5):581-5. DOI: 10.1111/j.1743-6109.2006.00157.x. View

10.

Merabishvili M, Pirnay J, Verbeken G, Chanishvili N, Tediashvili M, Lashkhi N . Quality-controlled small-scale production of a well-defined bacteriophage cocktail for use in human clinical trials. PLoS One. 2009; 4(3):e4944. PMC: 2654153. DOI: 10.1371/journal.pone.0004944. View

11.

Marza J, Soothill J, Boydell P, Collyns T . Multiplication of therapeutically administered bacteriophages in Pseudomonas aeruginosa infected patients. Burns. 2006; 32(5):644-6. DOI: 10.1016/j.burns.2006.02.012. View

12.

Jikia D, Chkhaidze N, Imedashvili E, Mgaloblishvili I, Tsitlanadze G, Katsarava R . 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. 2005; 30(1):23-6. DOI: 10.1111/j.1365-2230.2004.01600.x. View

13.

McVay C, Velasquez M, Fralick J . Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model. Antimicrob Agents Chemother. 2007; 51(6):1934-8. PMC: 1891379. DOI: 10.1128/AAC.01028-06. View

14.

Pirnay J, De Vos D, Cochez C, Bilocq F, Pirson J, Struelens M . Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone. J Clin Microbiol. 2003; 41(3):1192-202. PMC: 150314. DOI: 10.1128/JCM.41.3.1192-1202.2003. View

15.

Taddonio T, Thomson P, Tait M, Prasad J, Feller I . Rapid quantification of bacterial and fungal growth in burn wounds: biopsy homogenate Gram stain versus microbial culture results. Burns Incl Therm Inj. 1988; 14(3):180-4. DOI: 10.1016/0305-4179(88)90035-6. View

16.

Endersen L, OMahony J, Hill C, Ross R, McAuliffe O, Coffey A . Phage therapy in the food industry. Annu Rev Food Sci Technol. 2014; 5:327-49. DOI: 10.1146/annurev-food-030713-092415. View

17.

Kumari S, Harjai K, Chhibber S . Bacteriophage versus antimicrobial agents for the treatment of murine burn wound infection caused by Klebsiella pneumoniae B5055. J Med Microbiol. 2010; 60(Pt 2):205-210. DOI: 10.1099/jmm.0.018580-0. View

18.

Sulakvelidze A, Alavidze Z, Morris Jr J . Bacteriophage therapy. Antimicrob Agents Chemother. 2001; 45(3):649-59. PMC: 90351. DOI: 10.1128/AAC.45.3.649-659.2001. View

19.

Verbeken G, Pirnay J, Lavigne R, Jennes S, De Vos D, Casteels M . Call for a dedicated European legal framework for bacteriophage therapy. Arch Immunol Ther Exp (Warsz). 2014; 62(2):117-29. PMC: 3950567. DOI: 10.1007/s00005-014-0269-y. View

20.

Hsueh P, Teng L, Yang P, Chen Y, Ho S, Luh K . Persistence of a multidrug-resistant Pseudomonas aeruginosa clone in an intensive care burn unit. J Clin Microbiol. 1998; 36(5):1347-51. PMC: 104826. DOI: 10.1128/JCM.36.5.1347-1351.1998. View