Bacteriophage as an Antimicrobial against Pseudomonas aeruginosa in Burn Patients
Kendall Turner
Introduction Pseudomonas aeruginosa is a gram negative bacterium and opportunistic human pathogen with intrinsic antibiotic resistance capabilities and adaptive mechanisms.1 The organism has the third highest incident rate of nosocomial infections in burn patients, composing 9.00 to 18.30% of burn infections.2 Furthermore, P. aeruginosa is a major cause of skin graft loss in burn patients.3 Increasing antibiotic resistance of the organism has created a need for alternative effective therapies. Lytic bacteriophages target and parasitize bacteria and may provide a new and effective approach to treating P. aeruginosa burn wound infections. Methods A literature search was conducted via the PubMed database and included for consideration peer reviewed research journal articles published within the last five years. Keywords included “Pseudomonas aeruginosa”, “bacteriophage”, “phage”, “burn patient”, “burn wound”, “epithelium” and considered basic research, animal models, and clinical trials as available. Research articles were analyzed for quality of data and impact factors of the journals. Lung and catheter related infections were excluded. Results Multiple strains of bacteriophages have been identified as potential candidates against Pseudomonas aeruginosa infection and are commonly found in the Podoviridae and Myoviridae families. In vitro studies have shown MAG1 to reduce biofilm effectively over a long period of time resulting in less selection for phage-resistant clones due to a YefM antitoxin homolog.4 In vivo studies of ᶲPan70 on a burned mouse model have demonstrated 80-100% survival rates compared to its 0% survival of controls.5 phiYY phages identified in China provide the first discovered dsRNA phage against Pseudomonas aeruginosa and possesses a broad host range and muramidase lysin protein effective against multi-drug resistant bacteria.6 Only one clinical trial has been published within the last five years, and while it does not demonstrate more effectiveness than antibiotics, phage therapy does not appear to result in adverse effects.7 Furthermore, in vitro experiments provide evidence that the combination of phage and antibiotic is more effective than either treatment alone. This is due to the ability of the phage to break own the bacteria cell’s biofilm layer, leaving it exposed to the effects of antibiotics. Combination therapy essentially blocks both possible pathways of resistance evolution by P. aeruginosa.8 Conclusion Many promising lytic phages against Pseudomonas aeruginosa have been identified. However, phage therapy specifically against Pseudomonas aeruginosa is very much still in early stages. Randomized clinical control trials of phage only and phage-antibiotic therapies are needed to establish true efficacy and reliability of phage treatment.
- Chen, Selina SP, and Ralph Rudoy. Pseudomonas Infection. MedScape. http://emedicine.medscape.com/article/970904-overview#showall. Published March 9, 2016. Accessed March 23, 2017.
- Leseva, M et al. Nosocomial infections in burn patients: etiology, antimicrobial resistance, means to control. Annals of Burns and Fire Disasters. 2013;26(1): 5-11.
- Coetzee E, Rode H, Kahn D. Pseudomonas aeruginosa burn wound infection in a dedicated paediatric burns unit. South African Journal Of Surgery. 2013;51(2):50-53.
- Kiatek, Magdalena et al. Isolation of bacteriophages and their application to control Pseudomonas aeruginosa in planktonic and biofilm models. Research in Microbiology. 2017;168:194-207
- Holguin, Angela V et al. Phage ᶲPan70, a Putative Temperate Phage, Controls Pseudomonas aeruginosa in Planktonic, Biofilm and Burn Mouse Model Assays. Viruses. 2015;7:4602-2623.
- Yang Y, Lu S, Shen W, et al. Characterization of the first double-stranded RNA bacteriophage infecting Pseudomonas aeruginosa. Scientific Reports. 2016;6:38795.
- Rose, Thomas et al. Experimental phage therapy of burn wound infection: difficult first steps. Int J Burn Trauma. 2014;4(2):66-73.
- Chaudhry, Waqas Nasir et al. Synergy and Order Effects of Antibiotics and Phages in Killing Pseudomonas aeruginosa Biofilms. PLoS One. 2017;12(1):e0168615.