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Complications in Orthopedic Trauma Surgery: Fracture-Related Infection

  • Marc Antoine Burch
  • T. Fintan Moriarty
  • Richard Kuehl
  • Andrew Foster
  • Mario MorgensternEmail author
Chapter
  • 94 Downloads

Abstract

Fracture-related infection (FRI), in particular when associated with internal fixation hardware, is one of the most dreaded complications in orthopedic trauma surgery. Often hard to diagnose, these infections require input from both surgical and microbiological specialists. As such, these infections extend beyond the sole control of basic orthopedic surgery and demand the input of a multidisciplinary team of specialists in order to be adequately and comprehensively treated. FRI can lead to compromised new bone formation, bone necrosis, and failure for the fracture to heal. It can also result in considerable bone defects created when the infected necrotic bone is surgically removed. The reconstruction of these large bone defects can become a significant, secondary challenge, even for experienced surgeons. The burden of FRI is demonstrated not only in terms of the costs of repeated operative revision and prolonged hospital stay, but also in morbidity and loss of function for the affected patient. In this chapter we summarize the current clinical practices in the diagnosis and management of FRI. In addition, we list several domains in which scientific and technical developments are most needed, such as antimicrobial delivery and diagnostics, and which have the greatest potential to impact clinical practice.

Keywords

Fracture-related infection Orthopedic device-related infection Fracture Osteomyelitis Bacterial infection Biofilm 

References

  1. 1.
    Metsemakers WJ, Morgenstern M, McNally MA et al (2018) Fracture-related infection: a consensus on definition from an international expert group. Injury 49:505–510CrossRefGoogle Scholar
  2. 2.
    Metsemakers WJ, Kortram K, Morgenstern M et al (2018) Definition of infection after fracture fixation: a systematic review of randomized controlled trials to evaluate current practice. Injury 49:497–504CrossRefGoogle Scholar
  3. 3.
    Willenegger H, Roth B (1986) Treatment tactics and late results in early infection following osteosynthesis. Unfallchirurgie 12:241–246CrossRefGoogle Scholar
  4. 4.
    Thomer L, Schneewind O, Missiakas D (2016) Pathogenesis of Staphylococcus aureus bloodstream infections. Annu Rev Pathol 11:343–364CrossRefGoogle Scholar
  5. 5.
    Nishitani K, de Mesy Bentley KL, Daiss JL (2016) Implant-associated biofilm. Principles of orthopedic infection management. AO Foundation, DavosGoogle Scholar
  6. 6.
    Nguyen TH, Park MD, Otto M (2017) Host response to Staphylococcus epidermidis colonization and infections. Front Cell Infect Microbiol 7:90PubMedGoogle Scholar
  7. 7.
    Sabate Bresco M, Harris LG, Thompson K et al (2017) Pathogenic mechanisms and host interactions in Staphylococcus epidermidis device-related infection. Front Microbiol 8:1401CrossRefGoogle Scholar
  8. 8.
    Gahukamble AD, McDowell A, Post V et al (2014) Propionibacterium acnes and Staphylococcus lugdunensis cause pyogenic osteomyelitis in an intramedullary nail model in rabbits. J Clin Microbiol 52:1595–1606CrossRefGoogle Scholar
  9. 9.
    Lourtet-Hascoet J, Bicart-See A, Felice MP, Giordano G, Bonnet E (2016) Staphylococcus lugdunensis, a serious pathogen in periprosthetic joint infections: comparison to Staphylococcus aureus and Staphylococcus epidermidis. Int J Infect Dis 51:56–61CrossRefGoogle Scholar
  10. 10.
    Lee K, Lee KM, Kim D, Yoon SS (2017) Molecular determinants of the thickened matrix in a dual-species Pseudomonas aeruginosa and Enterococcus faecalis biofilm. Appl Environ Microbiol 83Google Scholar
  11. 11.
    Frank KL, Guiton PS, Barnes AM et al (2013) AhrC and Eep are biofilm infection-associated virulence factors in Enterococcus faecalis. Infect Immun 81:1696–1708CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Castillo Pedraza MC, Novais TF, Faustoferri RC et al (2017) Extracellular DNA and lipoteichoic acids interact with exopolysaccharides in the extracellular matrix of Streptococcus mutans biofilms. Biofouling 33:722–740CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Chao Y, Marks LR, Pettigrew MM, Hakansson AP (2014) Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease. Front Cell Infect Microbiol 4:194PubMedGoogle Scholar
  14. 14.
    Nguyen L, Minville V, Bensafi H et al (2007) Open leg fracture with Bacillus cereus infection. Ann Franc D’anesth Reanim 26:780–783CrossRefGoogle Scholar
  15. 15.
    Trampuz A, Zimmerli W (2006) Diagnosis and treatment of infections associated with fracture-fixation devices. Injury 37(Suppl 2):S59–S66CrossRefGoogle Scholar
  16. 16.
    Osterblad M, Hakanen A, Manninen R et al (2000) A between-species comparison of antimicrobial resistance in enterobacteria in fecal flora. Antimicrob Agents Chemother 44:1479–1484CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Berkes M, Obremskey WT, Scannell B et al (2010) Maintenance of hardware after early postoperative infection following fracture internal fixation. J Bone Joint Surg Am 92:823–828CrossRefGoogle Scholar
  18. 18.
    Zaid M, Chavez MR, Carrasco AE et al (2019) Cutibacterium (formerly Propionibacterium) acnes clavicular infection. J Bone Joint Infect 4:40–49CrossRefGoogle Scholar
  19. 19.
    Patel A, Calfee RP, Plante M, Fischer SA, Green A (2009) Propionibacterium acnes colonization of the human shoulder. J Shoulder Elbow Surg 18:897–902CrossRefGoogle Scholar
  20. 20.
    Ibnoulkhatib A, Lacroix J, Moine A et al (2012) Post-traumatic bone and/or joint limb infections due to Clostridium spp. Orthop Traumatol Surg Res 98:696–705CrossRefGoogle Scholar
  21. 21.
    Azzam K, Parvizi J, Jungkind D et al (2009) Microbiological, clinical, and surgical features of fungal prosthetic joint infections: a multi-institutional experience. J Bone Joint Surg Am 91(Suppl 6):142–149CrossRefGoogle Scholar
  22. 22.
    Joo HS, Otto M (2012) Molecular basis of in vivo biofilm formation by bacterial pathogens. Chem Biol 19:1503–1513CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Stewart PS (2015) Antimicrobial tolerance in biofilms. Microbiol Spectr 3Google Scholar
  24. 24.
    Kuehl R, Tschudin-Sutter S, Morgenstern M et al (2019) Time-dependent differences in management and microbiology of orthopaedic internal fixation-associated infections: an observational prospective study with 229 patients. Clin Microbiol Infect 25:76–81CrossRefGoogle Scholar
  25. 25.
    Metsemakers WJ, Onsea J, Neutjens E et al (2017) Prevention of fracture-related infection: a multidisciplinary care package. Int Orthop 41:2457–2469CrossRefGoogle Scholar
  26. 26.
    Patzakis MJ, Wilkins J (1989) Factors influencing infection rate in open fracture wounds. Clin Orthop Relat Res 243:36–40Google Scholar
  27. 27.
    Kortram K, Bezstarosti H, Metsemakers WJ, Raschke MJ, Van Lieshout EMM, Verhofstad MHJ (2017) Risk factors for infectious complications after open fractures; a systematic review and meta-analysis. Int Orthop 41:1965–1982CrossRefGoogle Scholar
  28. 28.
    Yim GH, Hardwicke JT (2018) The evolution and interpretation of the Gustilo and Anderson classification. J Bone Joint Surg Am 100:e152CrossRefGoogle Scholar
  29. 29.
    Gustilo RB, Anderson JT (1976) Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses. J Bone Joint Surg Am 58:453–458CrossRefGoogle Scholar
  30. 30.
    Chang Y, Kennedy SA, Bhandari M et al (2015) Effects of antibiotic prophylaxis in patients with open fracture of the extremities: a systematic review of randomized controlled trials. JBJS Rev 3Google Scholar
  31. 31.
    Luchette FA, Borzotta AP, Croce MA et al (2000) Practice management guidelines for prophylactic antibiotic use in penetrating abdominal trauma: the EAST Practice Management Guidelines Work Group. J Trauma 48:508–518CrossRefGoogle Scholar
  32. 32.
    Dunkel N, Pittet D, Tovmirzaeva L et al (2013) Short duration of antibiotic prophylaxis in open fractures does not enhance risk of subsequent infection. Bone Joint J 95-B:831–837CrossRefGoogle Scholar
  33. 33.
    Anderson A, Miller AD, Brandon BP (2011) Antimicrobial prophylaxis in open lower extremity fractures. Open Access Emerg Med 3:7–11PubMedGoogle Scholar
  34. 34.
    Thakore RV, Francois EL, Nwosu SK et al (2017) The Gustilo-Anderson classification system as predictor of nonunion and infection in open tibia fractures. Eur J Trauma Emerg Surg 43:651–656CrossRefGoogle Scholar
  35. 35.
    Guerra MTE, Gregio FM, Bernardi A, Castro CC (2017) Infection rate in adult patients with open fractures treated at the emergency hospital and at the ULBRA university hospital in Canoas, Rio Grande do Sul, Brazil. Rev Brasil Ortop 52:544–548CrossRefGoogle Scholar
  36. 36.
    Morgenstern M, Vallejo A, McNally MA et al (2018) The effect of local antibiotic prophylaxis when treating open limb fractures: a systematic review and meta-analysis. Bone Joint Res 7:447–456CrossRefGoogle Scholar
  37. 37.
    Otte JE, Politi JR, Chambers B, Smith CA (2017) Intrawound vancomycin powder reduces early prosthetic joint infections in revision hip and knee arthroplasty. Surg Technol Int 30:284–289PubMedGoogle Scholar
  38. 38.
    Sweet FA, Roh M, Sliva C (2011) Intrawound application of vancomycin for prophylaxis in instrumented thoracolumbar fusions: efficacy, drug levels, and patient outcomes. Spine 36:2084–2088CrossRefGoogle Scholar
  39. 39.
    Bakhsheshian J, Dahdaleh NS, Lam SK, Savage JW, Smith ZA (2015) The use of vancomycin powder in modern spine surgery: systematic review and meta-analysis of the clinical evidence. World Neurosurg 83:816–823CrossRefGoogle Scholar
  40. 40.
    Singh K, Bauer JM, LaChaud GY, Bible JE, Mir HR (2015) Surgical site infection in high-energy peri-articular tibia fractures with intra-wound vancomycin powder: a retrospective pilot study. J Orthop Traumatol 16:287–291CrossRefGoogle Scholar
  41. 41.
    Lawing CR, Lin FC, Dahners LE (2015) Local injection of aminoglycosides for prophylaxis against infection in open fractures. J Bone Joint Surg Am 97:1844–1851CrossRefGoogle Scholar
  42. 42.
    Lovallo J, Helming J, Jafari SM et al (2014) Intraoperative intra-articular injection of gentamicin: will it decrease the risk of infection in total shoulder arthroplasty? J Shoulder Elbow Surg 23:1272–1276CrossRefGoogle Scholar
  43. 43.
    Shiels SM, Tennent DJ, Wenke JC (2018) Topical rifampin powder for orthopedic trauma part I: Rifampin powder reduces recalcitrant infection in a delayed treatment musculoskeletal trauma model. J Orthop Res 36:3136–3141CrossRefGoogle Scholar
  44. 44.
    Morgenstern M, Kuhl R, Eckardt H et al (2018) Diagnostic challenges and future perspectives in fracture-related infection. Injury 49(Suppl 1):S83–S90CrossRefGoogle Scholar
  45. 45.
    Lee YJ, Sadigh S, Mankad K, Kapse N, Rajeswaran G (2016) The imaging of osteomyelitis. Quant Imaging Med Surg 6:184–198CrossRefGoogle Scholar
  46. 46.
    Rajashanker B, Whitehouse RW (2015) Chapter 53. Bone, joint and spinal infection. In: Grainger & Allison’s diagnostic radiology, 6th edn. Churchill Livingstone, New York, pp 1241–1242Google Scholar
  47. 47.
    Mettler F, Guiberteau M (2012) Chapter 8. Skeletal system. In: Essentials of nuclear medicine imaging, 6th edn. Saunders Elsevier, Philadelphia, pp 296–300Google Scholar
  48. 48.
    Christian S, Kraas J, Conway WF (2007) Musculoskeletal infections. Semin Roentgenol 42:92–101CrossRefGoogle Scholar
  49. 49.
    Palestro CJ, Torres MA (1997) Radionuclide imaging in orthopedic infections. Semin Nucl Med 27:334–345CrossRefGoogle Scholar
  50. 50.
    Al-Sheikh W, Sfakianakis GN, Mnaymneh W et al (1985) Subacute and chronic bone infections: diagnosis using In-111, Ga-67 and Tc-99m MDP bone scintigraphy, and radiography. Radiology 155:501–506CrossRefGoogle Scholar
  51. 51.
    Govaert GA, FF IJ, McNally M, McNally E, Reininga IH, Glaudemans AW (2017) Accuracy of diagnostic imaging modalities for peripheral post-traumatic osteomyelitis—a systematic review of the recent literature. Eur J Nucl Med Mol Imaging 44:1393–1407CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Glaudemans AW, de Vries EF, Vermeulen LE, Slart RH, Dierckx RA, Signore A (2013) A large retrospective single-centre study to define the best image acquisition protocols and interpretation criteria for white blood cell scintigraphy with (9)(9)mTc-HMPAO-labelled leucocytes in musculoskeletal infections. Eur J Nucl Med Mol Imaging 40:1760–1769CrossRefGoogle Scholar
  53. 53.
    van den Kieboom J, Bosch P, Plate JDJ et al (2018) Diagnostic accuracy of serum inflammatory markers in late fracture-related infection: a systematic review and meta-analysis. Bone Joint J 100-B:1542–1550CrossRefGoogle Scholar
  54. 54.
    Xie K, Dai K, Qu X, Serum YM (2017) Synovial fluid interleukin-6 for the diagnosis of periprosthetic joint infection. Sci Rep 7:1496CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Portillo ME, Salvadó M, Trampuz A et al (2015) Improved diagnosis of orthopedic implant-associated infection by inoculation of sonication fluid into blood culture bottles. J Clin Microbiol 53(5):1622–1627CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Aggarwal VK, Higuera C, Deirmengian G, Parvizi J, Austin MS (2013) Swab cultures are not as effective as tissue cultures for diagnosis of periprosthetic joint infection. Clin Orthop Relat Res 471:3196–3203CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Yano MH, Klautau GB, da Silva CB et al (2014) Improved diagnosis of infection associated with osteosynthesis by use of sonication of fracture fixation implants. J Clin Microbiol 52:4176–4182CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Vaudaux P, Kelley WL, Lew DP (2006) Staphylococcus aureus small colony variants: difficult to diagnose and difficult to treat. Clin Infect Dis 43:968–970CrossRefGoogle Scholar
  59. 59.
    Ronde-Oustau C, Lustig S, Dupieux C, Ferry T, Lyon BJ (2017) Implant-associated ESBL-Klebsiella pneumonia producing small colony variant bone and joint infection in a healthy 40-year-old man. BMJ Case Rep 2017Google Scholar
  60. 60.
    Tande AJ, Osmon DR, Greenwood-Quaintance KE, Mabry TM, Hanssen AD, Patel R (2014) Clinical characteristics and outcomes of prosthetic joint infection caused by small colony variant staphylococci. MBio 5:e01910–e01914CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Proctor RA, von Eiff C, Kahl BC et al (2006) Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 4:295–305CrossRefGoogle Scholar
  62. 62.
    Butler-Wu SM, Burns EM, Pottinger PS et al (2011) Optimization of periprosthetic culture for diagnosis of Propionibacterium acnes prosthetic joint infection. J Clin Microbiol 49:2490–2495CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Post V, Richards R, Moriarty TF (2016) Microbiology. In: Principles of orthopedic infection management. Georg Thieme Verlag, Stuttgart, pp 29–44Google Scholar
  64. 64.
    Renz N, Cabric S, Morgenstern C, Schuetz MA, Trampuz A (2018) Value of PCR in sonication fluid for the diagnosis of orthopedic hardware-associated infections: has the molecular era arrived? Injury 49:806–811CrossRefGoogle Scholar
  65. 65.
    Panousis K, Grigoris P, Butcher I, Rana B, Reilly JH, Hamblen DL (2005) Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92 cases. Acta Orthop 76:341–346CrossRefGoogle Scholar
  66. 66.
    Kramer AAO, Below H et al (2013) Wound antiseptics today—an overview. Antiseptics in surgery—update 2013. Lindqvist Book Publishing, Berlin, pp 85–111Google Scholar
  67. 67.
    Wouthyzen-Bakker M, Benito N, Soriano A (2017) The effect of preoperative antimicrobial prophylaxis on intraoperative culture results in patients with a suspected or confirmed prosthetic joint infection: a systematic review. J Clin Microbiol 55(9):2765–2774CrossRefGoogle Scholar
  68. 68.
    Rittmann WW, Perren S (1974) Cortical bone healing after internal fixation and infection. Springer Verlag, BerlinCrossRefGoogle Scholar
  69. 69.
    Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE (1998) Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group. JAMA 279:1537–1541CrossRefGoogle Scholar
  70. 70.
    Tschudin-Sutter S, Frei R, Dangel M et al (2016) Validation of a treatment algorithm for orthopaedic implant-related infections with device-retention-results from a prospective observational cohort study. Clin Microbiol Infect 22:457 e1–457 e9CrossRefGoogle Scholar
  71. 71.
    Zimmerli W (2015) Orthopaedic implant-associated infections: update of antimicrobial therapy. Der Orthopade 44:961–966CrossRefGoogle Scholar
  72. 72.
    Jefferson KK, Goldmann DA, Pier GB (2005) Use of confocal microscopy to analyze the rate of vancomycin penetration through Staphylococcus aureus biofilms. Antimicrob Agents Chemother 49:2467–2473CrossRefGoogle Scholar
  73. 73.
    Zimmerli W, Sendi P (2019) Role of Rifampin against Staphylococcal biofilm infections in vitro, in animal models, and in orthopedic-device-related infections. Antimicrob Agents Chemother 63:e01746PubMedPubMedCentralGoogle Scholar
  74. 74.
    Metsemakers WJ, Kuehl R, Moriarty TF et al (2018) Infection after fracture fixation: current surgical and microbiological concepts. Injury 49:511–522CrossRefGoogle Scholar
  75. 75.
    Calhoun JH, Henry SL, Anger DM, Cobos JA, Mader JT (1993) The treatment of infected nonunions with gentamicin-polymethylmethacrylate antibiotic beads. Clin Orthop Relat Res:23–27Google Scholar
  76. 76.
    Rand BC, Penn-Barwell JG, Wenke JC (2015) Combined local and systemic antibiotic delivery improves eradication of wound contamination: an animal experimental model of contaminated fracture. Bone Joint J 97-B:1423–1427CrossRefGoogle Scholar
  77. 77.
    Webb JC, Gbejuade H, Lovering A, Spencer R (2013) Characterisation of in vivo release of gentamicin from polymethyl methacrylate cement using a novel method. Int Orthop 37:2031–2036CrossRefGoogle Scholar
  78. 78.
    Quintiliani R, Courvalin P (1995) Mechanisms of resistance to antimicrobial agents. In: Manual of clinical microbiology, 6th edn. ASM, Washington, DC, p 1319Google Scholar
  79. 79.
    Anguita-Alonso P, Rouse MS, Piper KE, Jacofsky DJ, Osmon DR, Patel R (2006) Comparative study of antimicrobial release kinetics from polymethylmethacrylate. Clin Orthop Relat Res 445:239–244PubMedGoogle Scholar
  80. 80.
    Likine EF, Seligson D (2019) Rifampin and tobramycin combination with PMMA antibiotic cement. Eur J Orthopaed Surg Traumatol Orthoped Traumatol 29:499–500CrossRefGoogle Scholar
  81. 81.
    Inzana JA, Schwarz EM, Kates SL, Awad HA (2016) Biomaterials approaches to treating implant-associated osteomyelitis. Biomaterials 81:58–71CrossRefGoogle Scholar
  82. 82.
    Zilberman M, Elsner JJ (2008) Antibiotic-eluting medical devices for various applications. J Control Release 130:202–215CrossRefGoogle Scholar
  83. 83.
    Bennett-Guerrero E, Ferguson TB Jr, Lin M et al (2010) Effect of an implantable gentamicin-collagen sponge on sternal wound infections following cardiac surgery: a randomized trial. JAMA 304:755–762CrossRefGoogle Scholar
  84. 84.
    Chaudhary S, Sen RK, Saini UC, Soni A, Gahlot N, Singh D (2011) Use of gentamicin-loaded collagen sponge in internal fixation of open fractures. Chin J Traumatol 14:209–214PubMedGoogle Scholar
  85. 85.
    Ferguson J, Diefenbeck M, McNally M (2017) Ceramic biocomposites as biodegradable antibiotic carriers in the treatment of bone infections. J Bone Joint Infect 2:38–51CrossRefGoogle Scholar
  86. 86.
    McKee MD, Li-Bland EA, Wild LM, Schemitsch EH (2010) A prospective, randomized clinical trial comparing an antibiotic-impregnated bioabsorbable bone substitute with standard antibiotic-impregnated cement beads in the treatment of chronic osteomyelitis and infected nonunion. J Orthop Trauma 24:483–490CrossRefGoogle Scholar
  87. 87.
    Craig J, Fuchs T, Jenks M et al (2014) Systematic review and meta-analysis of the additional benefit of local prophylactic antibiotic therapy for infection rates in open tibia fractures treated with intramedullary nailing. Int Orthop 38:1025–1030CrossRefGoogle Scholar
  88. 88.
    El-Husseiny M, Patel S, MacFarlane RJ, Haddad FS (2011) Biodegradable antibiotic delivery systems. J Bone Joint Surg 93:151–157CrossRefGoogle Scholar
  89. 89.
    Brady RA, O’May GA, Leid JG, Prior ML, Costerton JW, Shirtliff ME (2011) Resolution of Staphylococcus aureus biofilm infection using vaccination and antibiotic treatment. Infect Immun 79:1797–1803CrossRefGoogle Scholar
  90. 90.
    Lemire JA, Kalan L, Bradu A, Turner RJ (2015) Silver oxynitrate, an unexplored silver compound with antimicrobial and antibiofilm activity. Antimicrob Agents Chemother 59:4031–4039CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Moriarty TF, Kuehl R, Coenye T et al (2016) Orthopaedic device-related infection: current and future interventions for improved prevention and treatment. EFORT Open Rev 1:89–99CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Mansour SC, de la Fuente-Nunez C, Hancock RE (2015) Peptide IDR-1018: modulating the immune system and targeting bacterial biofilms to treat antibiotic-resistant bacterial infections. J Pept Sci 21:323–329CrossRefGoogle Scholar
  93. 93.
    De Brucker K, Delattin N, Robijns S et al (2014) Derivatives of the mouse cathelicidin-related antimicrobial peptide (CRAMP) inhibit fungal and bacterial biofilm formation. Antimicrob Agents Chemother 58:5395–5404CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Gil D, Shuvaev S, Frank-Kamenetskii A, Reukov V, Gross C, Vertegel A (2017) Novel antibacterial coating on orthopedic wires to eliminate pin tract infections. Antimicrob Agents Chemother 61:e00442CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Greene AH, Bumgardner JD, Yang Y, Moseley J, Haggard WO (2008) Chitosan-coated stainless steel screws for fixation in contaminated fractures. Clin Orthop Relat Res 466:1699–1704CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Jennings JA, Carpenter DP, Troxel KS et al (2015) Novel antibiotic-loaded point-of-care implant coating inhibits biofilm. Clin Orthop Relat Res 473:2270–2282CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    McConoughey SJ, Howlin R, Granger JF et al (2014) Biofilms in periprosthetic orthopedic infections. Future Microbiol 9:987–1007CrossRefGoogle Scholar
  98. 98.
    Whiteley M, Diggle SP, Greenberg EP (2017) Progress in and promise of bacterial quorum sensing research. Nature 551:313–320CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Hentzer M, Wu H, Andersen JB et al (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22:3803–3815CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Abedon ST, Kuhl SJ, Blasdel BG, Kutter EM (2011) Phage treatment of human infections. Bacteriophage 1:66–85CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Deresinski S (2009) Bacteriophage therapy: exploiting smaller fleas. Clin Infect Dis 48:1096–1101CrossRefGoogle Scholar
  102. 102.
    Sulakvelidze A, Kutter E (2005) Bacteriophage therapy in humans. In: Bacteriophages: biology and application. CRC, Boca Raton, FL, pp 381–436Google Scholar
  103. 103.
    Tkhilaishvili T, Lombardi L, Klatt AB, Trampuz A, Di Luca M (2018) Bacteriophage Sb-1 enhances antibiotic activity against biofilm, degrades exopolysaccharide matrix and targets persisters of Staphylococcus aureus. Int J Antimicrob Agents 52:842–853CrossRefGoogle Scholar
  104. 104.
    Henriksen K, Rorbo N, Rybtke ML et al (2019) P. aeruginosa flow-cell biofilms are enhanced by repeated phage treatments but can be eradicated by phage-ciprofloxacin combination. Pathog Dis 77:ftz011CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Marc Antoine Burch
    • 1
    • 2
  • T. Fintan Moriarty
    • 1
  • Richard Kuehl
    • 2
  • Andrew Foster
    • 1
  • Mario Morgenstern
    • 2
    Email author
  1. 1.AO Research Institute DavosDavosSwitzerland
  2. 2.Clinic for Orthopedics and Trauma Surgery, University Hospital of BaselBaselSwitzerland

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