Topical Polyethylene Glycol-Phage Ointment as a Therapy to Treat Burn-Wound Infection Using Mice Model
DOI:
https://doi.org/10.23851/mjs.v35i2.1477Keywords:
Phage, Phage therapy, P. aeruginosa, burn wound infection, PEG-phage ointmentAbstract
Background: One of the most significant problems facing public health today is antimicrobial resistance. Pseudomonas aeruginosa is considered one of the most prevalent causes of healthcare-associated illnesses. Objective: The use of phages as a potential alternative therapeutic method for treating bacterial infections has been the subject of significant research to solve this predicament. Methods: The P. aeruginosa isolates that caused infections of burn wounds were collected from three hospitals in Baghdad. The VITEK system diagnosed and examined the isolates for their antibiotic sensitivity. As well as the phages were isolated and purified from sewage water samples from different sewer stations. After these steps, phages were examined by transmission electron microscopy to ensure the order and the families of these phages, and the tests of lytic activities of phages on the P. aeruginosa isolates were done to determine the best lytic ability of them to use for treatment wounds infections. Results: Burn-wound infections swabs culture showed a positive culture for 109 isolates as the following P. aeruginosa in 76(69.72%), Staphylococcus aureus16(14.67%), Acinetobacter baumannii 9(8.25%), Klebsiella pneumoniae 5(4.58%), Escherichia .coli 3(2.75%) obtained from burn wound infections, had a significant level of resistance to several antibiotics. Four bacteriophages were isolated: KM1, KM2, KM3, KM4 and KM5. KM5 is a mixture of phages referred to as a cocktail. The four phages and their cocktail exhibited significant lytic activity against P. aeruginosa. A total of four monophages and a cocktail were utilized in the preparation of the PEG-phage ointment. Conclusions: All monophages and their cocktail could completely clear bacterial infection in 17 days. KM3 and KM4 PEG-phage ointments demonstrated more potent healing activity than standard, which required 12 days for full recovery, while the cocktail took 15 days (KM5). However, KM1 and KM2 took the same time as the standard, which is 17 days for burn wound infection treated with PEG-phage ointments, while the control, which did not receive any treatment, took 23 days to recover. KM1 and KM2 show less activity for healing burn wound infections from all five phage ointments.
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References
J. Friedstat, D. A. Brown, and B. Levi, "Chemical, electrical, and radiation injuries," Clinics in plastic surgery, vol. 44, no. 3, pp. 657-669, 2017.
M. G. Jeschke, M. E. van Baar, M. A. Choudhry, K. K. Chung, N. S. Gibran, and S. Logsetty, "Burn injury," Nature Reviews Disease Primers, vol. 6, no. 1, p. 11, 2020.
M. A. Khalil, G. M. El Maghraby, F. I. Sonbol, N. G. Allam, P. S. Ateya, and S. S. Ali, "Enhanced efficacy of some antibiotics in presence of silver nanoparticles against multidrug resistant pseudomonas aeruginosa recovered from burn wound infections," Frontiers in microbiology, vol. 12, p. 648 560, 2021.
N. Othman and D. Kendrick, "Epidemiology of burn injuries in the east mediterranean region: A systematic review," BMC public health, vol. 10, pp. 1-10, 2010.
C.-J. Fraenkel, G. Starlander, E. Tano, S. Sütterlin, and Å. Melhus, "The first swedish outbreak with vim-2-producing pseudomonas aeruginosa, occurring between 2006 and 2007, was probably due to contaminated hospital sinks," Microorganisms, vol. 11, no. 4, p. 974, 2023.
L. Danelishvili, L. S. Young, and L. E. Bermudez, "In vivo efficacy of phage therapy for mycobacterium avium infection as delivered by a nonvirulent mycobacterium," Microbial Drug Resistance, vol. 12, no. 1, pp. 1-6, 2006.
C. Kolenda, J. Josse, M. Medina, C. Fevre, S. Lustig, T. Ferry, and F. Laurent, "Evaluation of the activity of a combination of three bacteriophages alone or in association with antibiotics on staphylococcus aureus embedded in biofilm or internalized in osteoblasts," Antimicrobial agents and chemotherapy, vol. 64, no. 3, pp. 10-1128, 2020.
A. Alturki, "Burn wound infections; a review article," World Family Medicine, vol. 19, no. 5, pp. 111-116, 2021.
T. Chhibber, V. S. Gondil, and V. Sinha, "Development of chitosan-based hydrogel containing antibiofilm agents for the treatment of staphylococcus aureus-infected burn wound in mice," AAPS PharmSciTech, vol. 21, pp. 1-12, 2020.
N. Principi, E. Silvestri, and S. Esposito, "Advantages and limitations of bacteriophages for the treatment of bacterial infections," Frontiers in pharmacology, vol. 10, p. 513, 2019.
O. Sepúlveda-Robles, L. Kameyama, and G. Guarneros, "High diversity and novel species of pseudomonas aeruginosa bacteriophages," Applied and environmental microbiology, vol. 78, no. 12, pp. 4510-4515, 2012.
A. M. Pinto, M. A. Cerqueira, M. Bañobre-Lópes, L. M. Pastrana, and S. Sillankorva, "Bacteriophages for chronic wound treatment: From traditional to novel delivery systems," Viruses, vol. 12, no. 2, p. 235, 2020.
A. Zyman, A. Górski, and R. Międzybrodzki, "Phage therapy of wound-associated infections," Folia microbiologica, vol. 67, no. 2, pp. 193-201, 2022.
W. Hussain, M. W. Ullah, U. Farooq, A. Aziz, and S. Wang, "Bacteriophage-based advanced bacterial detection: Concept, mechanisms, and applications," Biosensors and Bioelectronics, vol. 177, p. 112 973, 2021.
M. M. Azevedo, C. Pina-Vaz, and A. G. Rodrigues, "The role of phage therapy in burn wound infections management: Advantages and pitfalls," Journal of Burn Care & Research, vol. 43, no. 2, pp. 336-342, 2022.
J. S. Marza, J. Soothill, P. Boydell, and T. Collyns, "Multiplication of therapeutically administered bacteriophages in pseudomonas aeruginosa infected patients," Burns, vol. 32, no. 5, pp. 644-646, 2006.
K. M. Caflisch, G. A. Suh, and R. Patel, "Biological challenges of phage therapy and proposed solutions: A literature review," Expert review of anti-infective therapy, vol. 17, no. 12, pp. 1011-1041, 2019.
R. J. Atterbury, A. M. Gigante, M. d. l. S. Rubio Lozano, R. D. Méndez Medina, G. Robinson, H. Alloush, P. A. Barrow, and V. M. Allen, "Reduction of salmonella contamination on the surface of chicken skin using bacteriophage," Virology Journal, vol. 17, no. 1, pp. 1-8, 2020.
S. Kumari, K. Harjai, and S. Chhibber, "Topical treatment of klebsiella pneumoniae b5055 induced burn wound infection in mice using natural products," The Journal of Infection in Developing Countries, vol. 4, no. 06, pp. 367-377, 2010.
B. A. Berryhill, D. L. Huseby, I. C. McCall, D. Hughes, and B. R. Levin, "Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of staphylococcus aureus infections," Proceedings of the National Academy of Sciences, vol. 118, no. 10, e2008007118, 2021.
B. L. Aghaee, M. Khan Mirzaei, M. Y. Alikhani, A. Mojtahedi, and C. F. Maurice, "Improving the inhibitory effect of phages against pseudomonas aeruginosa isolated from a burn patient using a combination of phages and antibiotics," Viruses, vol. 13, no. 2, p. 334, 2021.
A. S. André, I. Moutinho, J. N. Dias, and F. Aires-da-Silva, "In vivo phage display: A promising selection strategy for the improvement of antibody targeting and drug delivery properties," Frontiers in Microbiology, vol. 13, p. 962 124, 2022.
A. V. Holguı́n, G. Rangel, V. Clavijo, C. Prada, M. Mantilla, M. C. Gomez, E. Kutter, C. Taylor, P. C. Fineran, and A. F. G. Barrios, "Phage Φpan70, a putative temperate phage, controls pseudomonas aeruginosa in planktonic, biofilm and burn mouse model assays," Viruses, vol. 7, no. 8, pp. 4602-4623, 2015.
P. Jault, T. Leclerc, S. Jennes, J. P. Pirnay, Y.-A. Que, G. Resch, A. F. Rousseau, F. Ravat, H. Carsin, and R. Le Floch, "Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by pseudomonas aeruginosa (phagoburn): A randomised, controlled, double-blind phase 1/2 trial," The Lancet Infectious Diseases, vol. 19, no. 1, pp. 35-45, 2019.
S. Richter, L. Sercia, J. Branda, C.-A. D. Burnham, M. Bythrow, M. Ferraro, O. Garner, C. Ginocchio, R. Jennemann, and M. Lewinski, "Identification of enterobacteriaceae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the vitek ms system," European journal of clinical microbiology & infectious diseases, vol. 32, pp. 1571-1578, 2013.
S. Jassim, A. Abdulamir, and F. Abu Bakar, "Novel phage-based bio-processing of pathogenic escherichia coli and its biofilms," World Journal of Microbiology and Biotechnology, vol. 28, pp. 47-60, 2012.
J. J. Dennehy and S. T. Abedon, "Phage infection and lysis," Bacteriophages: biology, technology, therapy, pp. 341-383, 2021.
H. Ana, S. Rui, and A. Adelaide, "Reducing salmonella horizontal transmission during egg incubation by phage therapy," disease, vol. 10, no. 8, pp. 718-722, 2013.
A. M. King, E. Lefkowitz, M. J. Adams, and E. B. Carstens, Virus taxonomy: ninth report of the International Committee on Taxonomy of Viruses. Elsevier, 2011.
R. M. Dale, G. Schnell, and J. P. Wong, "Therapeutic efficacy of "nubiotics" against burn wound infection by pseudomonas aeruginosa," Antimicrobial agents and chemotherapy, vol. 48, no. 8, pp. 2918-2923, 2004.
A. Vieira, Y. Silva, A. Cunha, N. Gomes, H.-W. Ackermann, and A. Almeida, "Phage therapy to control multidrugresistant pseudomonas aeruginosa skin infections: In vitro and ex vivo experiments," European Journal of clinical microbiology & infectious diseases, vol. 31, pp. 3241-3249, 2012.
H.-W. Ackermann and M. S. DuBow, Viruses of prokaryotes. CRC press, 1987.
J. J. Dennehy and S. T. Abedon, "Phage infection and lysis," Bacteriophages: biology, technology, therapy, pp. 341-383, 2021.
S. T. Abedon, "Lysis from without," Bacteriophage, vol. 1, no. 1, pp. 46-49, 2011.
G. Aprea, A. R. D'Angelo, V. A. Prencipe, and G. Migliorati, "Bacteriophage morphological characterization by using transmission electron microscopy," Journal of Life Sciences, vol. 9, no. 1, pp. 214-220, 2015.
J. Madsen and T. Susi, "The abtem code: Transmission electron microscopy from first principles," Open Research Europe, vol. 1, no. 24, p. 24, 2021.
M. Kornienko, N. Kuptsov, R. Gorodnichev, D. Bespiatykh, A. Guliaev, M. Letarova, E. Kulikov, V. Veselovsky, M. Malakhova, and A. Letarov, "Contribution of podoviridae and myoviridae bacteriophages to the effectiveness of anti-staphylococcal therapeutic cocktails," Scientific reports, vol. 10, no. 1, p. 18 612, 2020.
S. O'flaherty, A. Coffey, R. Edwards, W. Meaney, G. Fitzgerald, and R. Ross, "Genome of staphylococcal phage k: A new lineage of myoviridae infecting gram-positive bacteria with a low g+ c content," Journal of bacteriology, vol. 186, no. 9, pp. 2862-2871, 2004.
C. M. Chibani, A. Farr, S. Klama, S. Dietrich, and H. Liesegang, "Classifying the unclassified: A phage classification method," Viruses, vol. 11, no. 2, p. 195, 2019.
Y. Zhu, J. Shang, C. Peng, and Y. Sun, "Phage family classification under caudoviricetes: A review of current tools using the latest ictv classification framework," Frontiers in Microbiology, vol. 13, p. 1 032 186, 2022.
B. J. Cairns and R. J. Payne, "Bacteriophage therapy and the mutant selection window," Antimicrobial agents and chemotherapy, vol. 52, no. 12, pp. 4344-4350, 2008.
L. L. Furfaro, M. S. Payne, and B. J. Chang, "Bacteriophage therapy: Clinical trials and regulatory hurdles,"Frontiers in cellular and infection microbiology, vol. 8, p. 376, 2018.
H. Kunisaki and Y. Tanji, "Intercrossing of phage genomes in a phage cocktail and stable coexistence with escherichia coli o157: H7 in anaerobic continuous culture," Applied microbiology and biotechnology, vol. 85, pp. 1533-1540, 2010.
A. J. Santiago, M. L. Burgos-Garay, L. Kartforosh, M. Mazher, and R. M. Donlan, "Bacteriophage treatment of carbapenemase-producing klebsiella pneumoniae in a multispecies biofilm: A potential biocontrol strategy for healthcare facilities," AIMS microbiology, vol. 6, no. 1, p. 43, 2020.
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