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Scientific Articles   |    
Bacteriophage Therapy in Implant-Related InfectionsAn Experimental Study
Cengiz Yilmaz, MD1; Mehmet Colak, MD1; Banu Coskun Yilmaz, MD1; Gulden Ersoz, MD1; Mzia Kutateladze, PhD2; Mehmet Gozlugol, MD1
1 Departments of Orthopedics and Traumatology (C.Y., M.C., and M.G.), Histology and Embryology (B.C.Y.), and Infectious Diseases and Clinical Bacteriology (G.E.), Mersin University Medical School, Mersin Universitesi Tip Fakultesi Hastanesi, Zeytinlibahce cd, 33070, Mersin, Turkey. E-mail address for C. Yilmaz: cyilmaz@doctor.com. E-mail address for M. Colak: drmcolak@hotmail.com. E-mail address for B.C. Yilmaz: bcoskuny@yahoo.com. E-mail address for G. Ersoz: ersoz@mersin.edu.tr. E-mail address for M. Gozlugol: mehmetgozlugol@gmail.com
2 G. Eliava Institute of Bacteriophages, Microbiology and Virology, 3 Gotua Street, Tbilisi 0160, Georgia. E-mail address: kutateladze@pha.ge
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A commentary by Dirk Jan F. Moojen, MD, PhD, is linked to the online version of this article at jbjs.org.

Investigation performed at Mersin University Medical School, Mersin, Turkey



Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. None of the authors, or their institution(s), have had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, no author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2013 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2013 Jan 16;95(2):117-125. doi: 10.2106/JBJS.K.01135
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Abstract

Background: 

Implant-related infections with bacteria resistant to multiple antibiotics represent one of the major problems in orthopaedic surgery. It was our hypothesis that local application of bacteriophages, which are bacteria-destroying viruses, would be effective against biofilm-forming bacteria.

Methods: 

An implant-related infection model was created using methicillin-resistant Staphylococcus aureus (MRSA) in forty-eight rats and Pseudomonas aeruginosa in another forty-eight rats. Each group was divided into four subgroups; one subgroup received a bacterium-specific bacteriophage (Sb-1 in the MRSA group and PAT14 in the Pseudomonas aeruginosa group), one received antibiotic for fourteen days (20 mg/kg/day teicoplanin in the MRSA group, and 120 mg/kg/day imipenem + cilastatin and 25 mg/kg/day amikacin in the Pseudomonas group), one received antibiotic and bacteriophage, and one received no treatment. Animals receiving bacteriophage therapy were injected locally with 107 bacteriophages in a 0.1-mL suspension on three consecutive days. All animals were killed on the fifteenth day after initiation of treatment, and the tibia was excised. Results were assessed with use of microbiology, light microscopy, and electron microscopy.

Results: 

In the MRSA group, the antibiotic administration significantly decreased the number of colony-forming units per subject in quantitative cultures (control subgroup, 50,586; bacteriophage, 30,788; antibiotic, 17,165; antibiotic + bacteriophage, 5000; p = 0.004 for the comparison of the latter group with the control). Biofilm was absent only in the antibiotic + bacteriophage subgroup. In the Pseudomonas group, the number of colony-forming units per subject in quantitative cultures was significantly lower in each treatment subgroup compared with the control subgroup (control subgroup, 14,749; bacteriophage, 6484 [p = 0.016]; antibiotic, 2619 [p = 0.01]; antibiotic + bacteriophage, 1705 [p < 0.001]). The value in the antibiotic + bacteriophage subgroup was also significantly lower than the values in the other subgroups (p = 0.006). Biofilm thickness did not differ significantly among the subgroups in the Pseudomonas group.

Conclusions: 

The addition of bacteriophage treatment to an appropriate antibiotic regimen helped to dissolve the biofilm of both types of bacteria studied. This effect on MRSA was more pronounced than that on Pseudomonas aeruginosa.

Clinical Relevance: 

The addition of bacteriophage therapy to a standard antibiotic regimen may represent a valuable adjunct for eradicating implant-related infections.

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    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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