In-vitro-Wirksamkeit von Bakteriophagen gegen die gängigen biofilmbildenden Bakterien in der Orthopädie und Unfallchirurgie

Zusammenfassung

Hintergrund

Biofilmbildende Bakterien stellen im klinischen Alltag eine große Herausforderung dar. Dies gilt insbesondere für den bakteriellen Befall von Prothesen oder Osteosynthesematerial in der Orthopädie und Unfallchirurgie. Die Therapie mit Bakteriophagen bildet hierfür in der Zukunft, neben chirurgischem Débridement und Antibiotikagabe, möglicherweise das 3. Standbein in der Therapie von Biofilmen.

Ziel der Arbeit

Das Ziel dieser Studie ist es, die aktuellen Daten zur In-vitro-Wirksamkeit von Bakteriophagen gegen Biofilm zu bündeln und somit als Wegweiser für weitere Studien zu dienen.

Material und Methoden

Es wurde eine systematische Literaturrecherche in der PubMed-Datenbank durchgeführt. Von Interesse waren in dieser Suche Studien, die sich mit der In-vitro-Wirksamkeit von Bakteriophagen gegen Biofilme der gängigen Bakterien in der Orthopädie und Unfallchirurgie beschäftigt haben.

Ergebnisse

Die Inhalte der durch die systematische Suche gefundenen Studien wurden in verschiedene Kategorien unterteilt und im Anschluss diskutiert. Von Interesse waren die Oberflächen und die Dauer, auf denen die Biofilme gezüchtet wurden. Weiterhin wurde auf die Wirksamkeit von Bakteriophagen und Antibiotika bei gemeinsamer Anwendung Rücksicht genommen. Abschließend wird dargestellt, wie die verschiedenen Autoren die Phagen erhielten, Sensibilitätstestungen durchführten und unter welchen Bedingungen (pH, Temperatur) die Phagen wirksam waren.

Schlussfolgerung

Die aktuellen Daten zur In-vitro-Wirksamkeit von Bakteriophagen zeigen sich hinsichtlich der Stabilität in sauren und basischen sowie in breiten Temperaturspektren vielversprechend. Es fehlen noch Studien, bei denen mehrwöchig gereifte Biofilme auf Oberflächen untersucht werden, die in der Orthopädie und Unfallchirurgie von Interesse sind.

Schlüsselwörter

Phagentherapie - Biofilm - periprothetische Gelenkinfektion - in vitro - Bakterien

• Literatur

• 1 Górski A, Jończyk-Matysiak E, Międzybrodzki R. et al. Phage Therapy: Beyond Antibacterial Action. Front Med (Lausanne) 2018; 5: 146
• 2 Donlan RM. Preventing biofilms of clinically relevant organisms using bacteriophage. Trends Microbiol 2009; 17: 66-72
• 3 Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002; 15: 167-193
• 4 Kutter E, Raya R, Carlson K. Molecular Mechanisms of Phage Infection. 2005.
• 5 Olszak T, Latka A, Roszniowski B. et al. Phage Life Cycles Behind Bacterial Biodiversity. Curr Med Chem 2017; 24: 3987-4001
• 6 Oppenheim AB, Kobiler O, Stavans J. et al. Switches in bacteriophage lambda development. Annu Rev Genet 2005; 39: 409-429
• 7 Young R. Phage lysis: three steps, three choices, one outcome. J Microbiol 2014; 52: 243-258
• 8 Hischebeth GT, Randau TM, Molitor E. et al. Comparison of bacterial growth in sonication fluid cultures with periprosthetic membranes and with cultures of biopsies for diagnosing periprosthetic joint infection. Diagn Microbiol Infect Dis 2016; 84: 112-115
• 9 Statistisches Bundesamt. Vollstationär behandelte Patientinnen und Patienten in Krankenhäusern. 2023 Zugriff am 20. Dezember 2024 unter: https://www.destatis.de/DE/Themen/Gesellschaft-Umwelt/Gesundheit/Krankenhaeuser/Tabellen/drg-operationen-insgesamt.html
• 10 Renz N, Trampuz A. Periprothetische Infektionen: aktueller Stand der Diagnostik und Therapie. Orthopädie & Rheuma 2015; 18: 20-28
• 11 Walter N, Rupp M, Hierl K. et al. Long-Term Patient-Related Quality of Life after Knee Periprosthetic Joint Infection. J Clin Med 2021; 10: 907
• 12 Walter N, Rupp M, Hinterberger T. et al. [Prosthetic infections and the increasing importance of psychological comorbidities: An epidemiological analysis for Germany from 2009 through 2019]. Orthopade 2021; 50: 859-865
• 13 Abisado RG, Benomar S, Klaus JR. et al. Bacterial Quorum Sensing and Microbial Community Interactions. mBio 2018; 9: e02331-17
• 14 Høyland-Kroghsbo NM, Maerkedahl RB, Svenningsen SL. A quorum-sensing-induced bacteriophage defense mechanism. mBio 2013; 4: e00362-12
• 15 Landini P, Antoniani D, Burgess JG. et al. Molecular mechanisms of compounds affecting bacterial biofilm formation and dispersal. Microbiol Biotechnol 2010; 86: 813-823
• 16 Ma L, Conover M, Lu H. et al. Assembly and development of the Pseudomonas aeruginosa biofilm matrix. PLoS Pathog 2009; 5: e1000354
• 17 Nealson KH, Platt T, Hastings JW. Cellular control of the synthesis and activity of the bacterial luminescent system. J Bacteriol 1970; 104: 313-322
• 18 Ng WL, Bassler BL. Bacterial quorum-sensing network architectures. Annu Rev Genet 2009; 43: 197-222
• 19 Papenfort K, Bassler BL. Quorum sensing signal-response systems in Gram-negative bacteria. Nat Rev Microbiol 2016; 14: 576-588
• 20 Spoering AL, Lewis K. Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials. J Bacteriol 2001; 183: 6746-6751
• 21 Melo LDR, Pinto G, Oliveira F. et al. The Protective Effect of Staphylococcus epidermidis Biofilm Matrix against Phage Predation. Viruses 2020; 12: 1076
• 22 Khalifa L, Brosh Y, Gelman D. et al. Targeting Enterococcus faecalis biofilms with phage therapy. Appl Environ Microbiol 2015; 81: 2696-2705
• 23 Danis-Wlodarczyk K, Vandenheuvel D, Jang HB. et al. A proposed integrated approach for the preclinical evaluation of phage therapy in Pseudomonas infections. Sci Rep 2016; 6: 28115
• 24 Save J, Que YA, Entenza JM. et al. Bacteriophages Combined With Subtherapeutic Doses of Flucloxacillin Act Synergistically Against Staphylococcus aureus Experimental Infective Endocarditis. J Am Heart Assoc 2022; 11: e023080
• 25 Whittard E, Redfern J, Xia G. et al. Phenotypic and Genotypic Characterization of Novel Polyvalent Bacteriophages With Potent In Vitro Activity Against an International Collection of Genetically Diverse Staphylococcus aureus. Front Cell Infect Microbiol 2021; 11: 698909
• 26 Fiscarelli EV, Rossitto M, Rosati P. et al. In Vitro Newly Isolated Environmental Phage Activity against Biofilms Preformed by Pseudomonas aeruginosa from Patients with Cystic Fibrosis. Microorganisms 2021; 9: 478
• 27 Camens S, Liu S, Hon K. et al. Preclinical Development of a Bacteriophage Cocktail for Treating Multidrug Resistant Pseudomonas aeruginosa Infections. Microorganisms 2021; 9: 2001
• 28 Plota M, Sazakli E, Giormezis N. et al. In Vitro Anti-Biofilm Activity of Bacteriophage K (ATCC 19685-B1) and Daptomycin against Staphylococci. Microorganisms 2021; 9: 1853
• 29 Sundaramoorthy NS, Thothathri S, Bhaskaran M. et al. Phages from Ganges River curtail in vitro biofilms and planktonic growth of drug resistant Klebsiella pneumoniae in a zebrafish infection model. AMB Express 2021; 11: 27
• 30 Cano EJ, Caflisch KM, Bollyky PL. et al. Phage Therapy for Limb-threatening Prosthetic Knee Klebsiella pneumoniae Infection: Case Report and In Vitro Characterization of Anti-biofilm Activity. Clin Infect Dis 2021; 73: e144-e151
• 31 Kifelew LG, Warner MS, Morales S. et al. Efficacy of Lytic Phage Cocktails on Staphylococcus aureus and Pseudomonas aeruginosa in Mixed-Species Planktonic Cultures and Biofilms. Viruses 2020; 12: 559
• 32 Wintachai P, Naknaen A, Thammaphet J. et al. Characterization of extended-spectrum-beta-lactamase producing Klebsiella pneumoniae phage KP1801 and evaluation of therapeutic efficacy in vitro and in vivo. Sci Rep 2020; 10: 11803
• 33 Racenis K, Kroica J, Rezevska D. et al. S. aureus Colonization, Biofilm Production, and Phage Susceptibility in Peritoneal Dialysis Patients. Antibiotics (Basel) 2020; 9: 582
• 34 Cobb LH, Park J, Swanson EA. et al. CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection. PLoS One 2019; 14: e0220421
• 35 Dakheel KH, Rahim RA, Neela VK. et al. Genomic analyses of two novel biofilm-degrading methicillin-resistant Staphylococcus aureus phages. BMC Microbiol 2019; 19: 114
• 36 Jeon J, Yong D. Two Novel Bacteriophages Improve Survival in Galleria mellonella Infection and Mouse Acute Pneumonia Models Infected with Extensively Drug-Resistant Pseudomonas aeruginosa. Appl Environ Microbiol 2019; 85: e02900-18
• 37 Al-Zubidi M, Widziolek M, Court EK. et al. Identification of Novel Bacteriophages with Therapeutic Potential That Target Enterococcus faecalis. Infect Immun 2019; 87: e00512-19
• 38 Oliveira A, Sousa JC, Silva AC. et al. Chestnut Honey and Bacteriophage Application to Control Pseudomonas aeruginosa and Escherichia coli Biofilms: Evaluation in an ex vivo Wound Model. Front Microbiol 2018; 9: 1725
• 39 Shlezinger M, Friedman M, Houri-Haddad Y. et al. Phages in a thermoreversible sustained-release formulation targeting E. faecalis in vitro and in vivo. PLoS One 2019; 14: e0219599
• 40 Taha OA, Connerton PL, Connerton IF. et al. Bacteriophage ZCKP1: A Potential Treatment for Klebsiella pneumoniae Isolated From Diabetic Foot Patients. Front Microbiol 2018; 9: 2127
• 41 Kumaran D, Taha M, Yi Q. et al. Does Treatment Order Matter? Investigating the Ability of Bacteriophage to Augment Antibiotic Activity against Staphylococcus aureus Biofilms. Front Microbiol 2018; 9: 127
• 42 Fong SA, Drilling A, Morales S. et al. Activity of Bacteriophages in Removing Biofilms of Pseudomonas aeruginosa Isolates from Chronic Rhinosinusitis Patients. Front Cell Infect Microbiol 2017; 7: 418
• 43 Singla S, Harjai K, Katare OP. et al. Encapsulation of Bacteriophage in Liposome Accentuates Its Entry in to Macrophage and Shields It from Neutralizing Antibodies. PLoS One 2016; 11: e0153777
• 44 Olszak T, Zarnowiec P, Kaca W. et al. In vitro and in vivo antibacterial activity of environmental bacteriophages against Pseudomonas aeruginosa strains from cystic fibrosis patients. Appl Microbiol Biotechnol 2015; 99: 6021-6033
• 45 Abdulamir AS, Jassim SA, Hafidh RR. et al. The potential of bacteriophage cocktail in eliminating Methicillin-resistant Staphylococcus aureus biofilms in terms of different extracellular matrices expressed by PIA, ciaA-D and FnBPA genes. Ann Clin Microbiol Antimicrob 2015; 14: 49
• 46 Mendes JJ, Leandro C, Mottola C. et al. In vitro design of a novel lytic bacteriophage cocktail with therapeutic potential against organisms causing diabetic foot infections. J Med Microbiol 2014; 63: 1055-1065
• 47 Cornelissen A, Ceyssens PJ, T’syen J. et al. The T7-related Pseudomonas putida phage phi15 displays virion-associated biofilm degradation properties. PLoS One 2011; 6: e18597
• 48 Knezevic P, Obreht D, Curcin S. et al. Phages of Pseudomonas aeruginosa: response to environmental factors and in vitro ability to inhibit bacterial growth and biofilm formation. J Appl Microbiol 2011; 111: 245-254
• 49 Cerca N, Oliveira R, Azeredo J. Susceptibility of Staphylococcus epidermidis planktonic cells and biofilms to the lytic action of staphylococcus bacteriophage K. Lett Appl Microbiol 2007; 45: 313-317
• 50 Chaudhry WN, Concepcion-Acevedo J, Park T. et al. Synergy and Order Effects of Antibiotics and Phages in Killing Pseudomonas aeruginosa Biofilms. PLoS One 2017; 12: e0168615
• 51 Oh HK, Hwang YJ, Hong HW. et al. Comparison of Enterococcus faecalis Biofilm Removal Efficiency among Bacteriophage PBEF129, Its Endolysin, and Cefotaxime. Viruses 2021; 13: 426
• 52 Melo LDR, Ferreira R, Costa AR. et al. Efficacy and safety assessment of two enterococci phages in an in vitro biofilm wound model. Sci Rep 2019; 9: 6643
• 53 Wroe JA, Johnson CT, Garcia AJ. Bacteriophage delivering hydrogels reduce biofilm formation in vitro and infection in vivo. J Biomed Mater Res A 2020; 108: 39-49
• 54 Curtin JJ, Donlan RM. Using bacteriophages to reduce formation of catheter-associated biofilms by Staphylococcus epidermidis. Antimicrob Agents Chemother 2006; 50: 1268-1275
• 55 Fu W, Forster T, Mayer O. et al. Bacteriophage cocktail for the prevention of biofilm formation by Pseudomonas aeruginosa on catheters in an in vitro model system. Antimicrob Agents Chemother 2010; 54: 397-404
• 56 Lehman SM, Donlan RM. Bacteriophage-mediated control of a two-species biofilm formed by microorganisms causing catheter-associated urinary tract infections in an in vitro urinary catheter model. Antimicrob Agents Chemother Appl 2015; 59: 1127-1137
• 57 Tan D, Zhang Y, Cheng M. et al. Characterization of Klebsiella pneumoniae ST11 Isolates and Their Interactions with Lytic Phages. Viruses 2019; 11: 1080
• 58 Tkhilaishvili T, Wang L, Perka C. et al. Using Bacteriophages as a Trojan Horse to the Killing of Dual-Species Biofilm Formed by Pseudomonas aeruginosa and Methicillin Resistant Staphylococcus aureus. Front Microbiol 2020; 11: 695
• 59 Wang L, Tkhilaishvili T, Trampuz A. et al. Evaluation of Staphylococcal Bacteriophage Sb-1 as an Adjunctive Agent to Antibiotics Against Rifampin-Resistant Staphylococcus aureus Biofilms. Front Microbiol 2020; 11: 602057
• 60 Magin V, Garrec N, Andres Y. Selection of Bacteriophages to Control In Vitro 24 h Old Biofilm of Pseudomonas Aeruginosa Isolated from Drinking and Thermal Water. Viruses 2019; 11: 749
• 61 Kirby AE. Synergistic action of gentamicin and bacteriophage in a continuous culture population of Staphylococcus aureus. PLoS One 2012; 7: e51017
• 62 Armon R, Kott Y. A simple, rapid and sensitive presence/absence detection test for bacteriophage in drinking water. J Appl Bacteriol 1993; 74: 490-496
• 63 Kutter E. Phage host range and efficiency of plating. Methods Mol Biol 2009; 501: 141-149
• 64 Mazzocco A, Waddell TE, Lingohr E. et al. Enumeration of bacteriophages using the small drop plaque assay system. Methods Mol Biol 2009; 501: 81-85
• 65 Schuster H. Bacteriophages, von M. H. Adams. Interscience Publishers, Inc., New York-London 1959. 1. Aufl., XVIII, 592 S., 26 Tab., 16 Abb., geb. £ 6.50. Angewandte Chemie 1962; 74: 164-164
• 66 Sambrook J, Russell DW. Molecular Cloning: A Laboratory Manual. New York: Cold Spring Harbour Laboratory Press; 2001
• 67 Appelmans R. Le dosage du bactériophage. Compt Rend Soc Biol 1921; 85: 701
• 68 Xie Y, Wahab L, Gill JJ. Development and Validation of a Microtiter Plate-Based Assay for Determination of Bacteriophage Host Range and Virulence. Viruses 2018; 10: 189
• 69 Stachurska X, Roszak M, Jabłońska J. et al. Double-Layer Agar (DLA) Modifications for the First Step of the Phage-Antibiotic Synergy (PAS) Identification. Antibiotics (Basel) 2021; 10: 1306