Subscribe to RSS
DOI: 10.1055/a-1989-0565
Local Administration of Antibiotics in Orthopedics and Traumatology
What is New 50 Years after the Development of Antibiotic Loaded PMMA Cements and -PMMA Bead Chains? Article in several languages: deutsch | English2022 marks the 50th anniversary of the development of the antibiotic loaded PMMA chain. The loading of bone cements with antibiotics was a major advance in the treatment of musculoskeletal infections and is still a proven standard today. The research and use of novel antibiotic carriers continues to be an important part of research in the context of musculoskeletal infections. The article provides an overview of the various local antibiotics available and their specifics. In addition, current adapted treatment concepts are discussed.
-
Lokale Antibiotika gewinnen in den Therapiestrategien von Infektionen des Bewegungsapparates zunehmend an Bedeutung.
-
Lokal applizierbare Antibiotikaträger ersetzen jedoch nicht das ausgiebige Débridement mit Entfernung von nekrotischem und infiziertem Gewebe sowie die Spülung in Kombination mit einer systemischen, teils biofilmwirksamen Antibiotikatherapie.
-
Mit antibiotischen Trägersubstanzen, die sich nach PMMA etabliert haben, z. B. Träger auf Kalziumbasis und Knochenersatzstoffe, kann nun auf die Entfernung der Substanzen verzichtet werden, und es sind einzeitige Therapiekonzepte möglich.
-
Der Einsatz lokaler Antibiotika und Antibiotikaträger erfordert umfangreiche Kenntnisse über Trägersubstanzen, deren Eigenschaften hinsichtlich Biokompatibilität und Abbaubarkeit sowie Elutionseigenschaften der eingesetzten Antibiotika und schließlich die Kenntnis der rechtlichen Rahmenbedingungen.
-
Der Artikel gibt einen Überblick über die verschiedenen lokal verfügbaren Antibiotika und deren Besonderheiten. Darüber hinaus werden aktuelle angepasste Behandlungskonzepte diskutiert.
-
Local antibiotics are becoming increasingly important in the therapeutic strategies for musculoskeletal infections.
-
Antibiotic carriers that can be applied locally cannot replace the basics of evidence-based treatment: extensive debridement with the removal of necrotic and infected tissue, implant management, and irrigation in combination with systemic, partly biofilm-effective, antibiotic therapy.
-
Once other antibiotic carrier substances, e.g., calcium-based carriers and bone substitutes, came into more general use after PMMA, the removal of these carrier substances was no longer necessary and single-stage therapy concepts became possible.
-
The use of local antibiotics and antibiotic carriers requires extensive knowledge of carrier substances, their properties in terms of biocompatibility and degradability, as well as the elution characteristics of the antibiotics used and, finally, a knowledge of the legal framework.
-
This article provides an overview of various topical antibiotics and their special features. In addition, current adapted treatment concepts are discussed.
Keywords
antibiotic carrier - PMMA - antibiotic beads - musculoskeletal infection - Periprosthetic joint Infection - PJI - fracture related infection - FRI - local antibioticsPublication History
Article published online:
28 September 2023
© 2023. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
Literatur
- 1 Otto-Lambertz C, Yagdiran A, Wallscheid F. et al. Periprosthetic infection in joint replacement: diagnosis and treatment. Dtsch Arztebl Int 2017; 114: 347-353
- 2 Revisionsendoprothetik der Hüftpfanne. Wirtz DC, Rader C, Reichel H. Heidelberg: Springer; 2008
- 3 Sporer SM, Paprosky WG. The use of a trabecular metal acetabular component and trabecular metal augment for severe acetabular defects. J Arthroplasty 2006; 21: 83-86
- 4 Yu R, Hofstaetter JG, Sullivan T. et al. Validity and reliability of the Paprosky acetabular defect classification. Clin Orthop Relat Res 2013; 471: 2259-2265
- 5 Winkler T, Trampuz A, Hardt S. et al. Periprothetische Infektion nach Hüftendoprothetik. Orthopade 2014; 43: 70-78
- 6 Bozic KJ, Kurtz SM, Lau E. et al. The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res 2010; 468: 45-51
- 7 Qasim SN, Swann A, Ashford R. The DAIR (debridement, antibiotics and implant retention) procedure for infected total knee replacement – a literature review. SICOT J 2017; 3: 2
- 8 Geipel U, Herrmann M. Das infizierte Implantat. Orthopäde 2005; 34: 119
- 9 Walter G, Gramlich Y. Periprothetische Infektionen. In: Engelhardt M, Raschke M. Orthopädie und Unfallchirurgie. BerlinHeidelberg: Springer; 2019: 1-25
- 10 Wang J, Calhoun JH, Mader JT. The application of bioimplants in the management of chronic osteomyelitis. Orthopedics 2002; 25: 1247-1252
- 11 Mader JT, Calhoun J, Cobos J. In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads. Antimicrob Agents Chemother 1997; 41: 415-418
- 12 Armstrong DG, Findlow AH, Oyibo SO. et al. The use of absorbable antibiotic-impregnated calcium sulphate pellets in the management of diabetic foot infections. Diabet Med 2001; 18: 942-943
- 13 Klemm K, Börner M. [Treatment of chronic osteomyelitis with gentamicin PMMA chains]. Unfallchirurgie 1986; 12: 128-131
- 14 Kanellakopoulou K, Galanopoulos I, Soranoglou V. et al. Treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with a synthetic carrier of calcium sulphate (Stimulan) releasing moxifloxacin. Int J Antimicrob Agents 2009; 33: 354-359
- 15 Jerosch J, Lindner N, Fuchs S. Ergebnisse der Langzeittherapie chronischer, posttraumatischer Osteomelytis mit Gentamicin PMMA-Ketten. Unfallchirurg 1995; 98: 338-343
- 16 Adams K, Couch L, Cierny G. et al. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res 1992; (278) 244-252
- 17 Blaha JD, Calhoun JH, Nelson CL. et al. Comparison of the clinical efficacy and tolerance of gentamicin PMMA beads on surgical wire versus combined and systemic therapy for osteomyelitis. Clin Orthop Relat Res 1993; (295) 8-12
- 18 Walenkamp GH, Kleijn LL, de Leeuw M. Osteomyelitis treated with gentamicin-PMMA beads: 100 patients followed for 1–12 years. Acta Orthop Scand 1998; 69: 518-522
- 19 Neut D, van de Belt H, Stokroos I. et al. Biomaterial-associated infection of gentamicin-loaded PMMA beads in orthopaedic revision surgery. J Antimicrob Chemother 2001; 47: 885-891
- 20 Heybeli N, Oktar FN, Ozyazgan S. et al. Low-cost antibiotic loaded systems for developing countries. Technol Health Care 2003; 11: 207-216
- 21 Kelm J, Anagnostakos K, Regitz T. et al. MRSA-Infektionen des Bewegungsapparats. Behandlung mit intraoperativ herstellbaren Gentamicin-Vancomycin-PMMA-Ketten. Chirurg 2004; 75: 988-995
- 22 Nelson CL, Griffin FM, Harrison BH. et al. In vitro elution characteristics of commercially and noncommercially prepared antibiotic PMMA beads. Clin Orthop Relat Res 1992; (284) 303-309
- 23 Walenkamp GH, Vree TB, van Rens TJ. Gentamicin-PMMA beads. Pharmacokinetic and nephrotoxicological study. Clin Orthop Relat Res 1986; (205) 171-183
- 24 DiCicco M, Duong T, Chu A. et al. Tobramycin and gentamycin elution analysis between two in situ polymerizable orthopedic composites. J Biomed Mater Res B Appl Biomater 2003; 65: 137-149
- 25 Rushton N. Applications of local antibiotic therapy. Eur J Surg Suppl 1997; 27-30
- 26 Wilson KJ, Cierny G, Adams KR. et al. Comparative evaluation of the diffusion of tobramycin and cefotaxime out of antibiotic-impregnated polymethylmethacrylate beads. J Orthop Res 1988; 6: 279-286
- 27 Ferguson JY, Dudareva M, Riley ND. et al. The use of a biodegradable antibiotic-loaded calcium sulphate carrier containing tobramycin for the treatment of chronic osteomyelitis: a series of 195 cases. Bone Joint J 2014; 96-B: 829-836
- 28 Turner TM, Urban RM, Hall DJ. et al. Local and systemic levels of tobramycin delivered from calcium sulfate bone graft substitute pellets. Clin Orthop Relat Res 2005; (437) 97-104
- 29 Chang W, Colangeli M, Colangeli S. et al. Adult osteomyelitis: debridement versus debridement plus Osteoset T pellets. Acta Orthop Belg 2007; 73: 238-243
- 30 Frommelt L. Prinzipien der Antibiotikabehandlung bei periprothetischen Infektionen. Orthopade 2004; 33: 822-828
- 31 Wahl P, Livio F, Jacobi M. et al. Systemic exposure to tobramycin after local antibiotic treatment with calcium sulphate as carrier material. Arch Orthop Trauma Surg 2011; 131: 657-662
- 32 Fleiter N, Walter G, Bosebeck H. et al. Clinical use and safety of a novel gentamicin-releasing resorbable bone graft substitute in the treatment of osteomyelitis/osteitis. Bone Joint Res 2014; 3: 223-229
- 33 Gramlich Y, Walter G, Gils J. et al. Erste Ergebnisse in der Anwendung resorbierbarer, lokaler Antibiotikaträger bei Rezidivosteomyelitiden. Z Orthop Unfall 2017; 155: 35-44
- 34 Gramlich Y. Procedure for single stage implant retention for chronic periprosthetic infection using topical degradable calcium-based antibiotics. Int Orthop 2019; 43: 1559-1566
- 35 Ferguson J, Diefenbeck M, McNally M. Ceramic biocomposites as biodegradable antibiotic carriers in the treatment of bone infections. J Bone Jt Infect 2017; 2: 38-51
- 36 The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 13.1. 2023 Accessed September 12, 2023 at: https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_13.1_Breakpoint_Tables.pdf
- 37 Stravinskas M, Horstmann P, Ferguson J. et al. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: in vitro and clinical release studies. Bone Joint Res 2016; 5: 427-435
- 38 Ferguson J, Athanasou N, Diefenbeck M. et al. Radiographic and histological analysis of a synthetic bone graft substitute eluting gentamicin in the treatment of chronic osteomyelitis. J Bone Jt Infect 2019; 4: 76-84
- 39 Niemann M, Graef F, Ahmad SS. et al. Outcome analysis of the use of Cerament® in patients with chronic osteomyelitis and corticomedullary defects. Diagnostics (Basel) 2022; 12: 1207
- 40 Gramlich Y, Johnson T, Kemmerer M. et al. Salvage procedure for chronic periprosthetic knee infection: the application of DAIR results in better remission rates and infection-free survivorship when used with topical degradable calcium-based antibiotics. Knee Surg Sports Traumatol Arthrosc 2020; 28: 2823-2834
- 41 Bennett-Guerrero E, Pappas TN, Koltun WA. et al. Gentamicin-collagen sponge for infection prophylaxis in colorectal surgery. N Engl J Med 2010; 363: 1038-1049
- 42 Kim KJ, Jeong HS, Ahn BH. et al. Clinical efficacy of the antibiotic-loaded collagen sponge during arthroscopic treatment of acute septic arthritis of the native knee. Orthop J Sports Med 2022; 10
- 43 van Vugt TAG, Walraven JMB, Geurts JAP. et al. Antibiotic-loaded collagen sponges in clinical treatment of chronic osteomyelitis: a systematic review. J Bone Joint Surg Am 2018; 100: 2153-2161
- 44 El-Husseiny M, Patel S, MacFarlane RJ. et al. Biodegradable antibiotic delivery systems. J Bone Joint Surg Br 2011; 93: 151-157
- 45 Ruszczak Z, Friess W. Collagen as a carrier for on-site delivery of antibacterial drugs. Adv Drug Deliv Rev 2003; 55: 1679-1698
- 46 García-García J, Azuara G, Fraile-Martinez O. et al. Modification of the polymer of a bone cement with biodegradable microspheres of PLGA and loading with daptomycin and vancomycin improve the response to bone tissue infection. Polymers (Basel) 2022; 14: 888
- 47 Inzana JA, Schwarz EM, Kates SL. et al. Biomaterials approaches to treating implant-associated osteomyelitis. Biomaterials 2016; 81: 58-71
- 48 Shariati A, Chegini Z, Ghaznavi-Rad E. et al. PLGA-based nanoplatforms in drug delivery for inhibition and destruction of microbial biofilm. Front Cell Infect Microbiol 2022; 12: 926363
- 49 Zhu M, Whittaker AK, Han FY. et al. Journey to the market: the evolution of biodegradable drug delivery systems. Appl Sci 2022; 12: 935
- 50 Zare EN, JamaledinNaserzadeh P. et al. Metal-based nanostructures/PLGA nanocomposites: antimicrobial activity, cytotoxicity, and their biomedical applications. ACS Appl Mater Interfaces 2020; 12: 3279-3300
- 51 Kasi G, Gnanasekar S, Zhang K. et al. Polyurethane-based composites with promising antibacterial properties. J Appl Polym Sci 2022; 139: 52181
- 52 Garvin K, Feschuk C. Polylactide-polyglycolide antibiotic implants. Clin Orthop Relat Res 2005; (437) 105-110
- 53 Basu A, Domb AJ. Recent advances in polyanhydride based biomaterials. Adv Mater 2018; 30: e1706815
- 54 Li LC, Deng J, Stephens D. Polyanhydride implant for antibiotic delivery--from the bench to the clinic. Adv Drug Deliv Rev 2002; 54: 963-986
- 55 Hench LL. The story of bioglass. J Mater Sci Mater Med 2006; 17: 967-978
- 56 Cunha MT, Murça MA, Nigro S. et al. In vitro antibacterial activity of bioactive glass S53P4 on multiresistant pathogens causing osteomyelitis and prosthetic joint infection. BMC Infect Dis 2018; 18: 157
- 57 Rivadeneira J, Gorustovich A. Bioactive glasses as delivery systems for antimicrobial agents. J Appl Microbiol 2017; 122: 1424-1437
- 58 Hench LL, Jones JR. Bioactive glasses: frontiers and challenges. Front Bioeng Biotechnol 2015; 3: 194
- 59 Winkler H. Treatment of chronic orthopaedic infection. EFORT Open Rev 2017; 2: 110-116
- 60 Winkler H, Haiden P. Allograft bone as antibiotic carrier. J Bone Jt Infect 2017; 2: 52-62
- 61 Giavaresi G, Meani E, Sartori M. et al. Efficacy of antibacterial-loaded coating in an in vivo model of acutely highly contaminated implant. Int Orthop 2014; 38: 1505-1512
- 62 Vertullo CJ, Quick M, Jones A. et al. A surgical technique using presoaked vancomycin hamstring grafts to decrease the risk of infection after anterior cruciate ligament reconstruction. Arthroscopy 2012; 28: 337-342
- 63 Baron JE, Shamrock AG, Cates WT. et al. Graft preparation with intraoperative vancomycin decreases infection after ACL reconstruction: a review of 1,640 cases. J Bone Joint Surg Am 2019; 101: 2187-2193
- 64 Eriksson K, Karlsson J. Local vancomycin in ACL reconstruction: a modern rationale (2016) for morbidity prevention and patient safety. Knee Surg Sports Traumatol Arthrosc 2016; 24: 2721-2723
- 65 Naendrup JH, Marche B, de Sa D. et al. Vancomycin-soaking of the graft reduces the incidence of septic arthritis following ACL reconstruction: results of a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc 2020; 28: 1005-1013
- 66 Rodriguez-Merchan EC, Ribbans WJ. The role of vancomycin-soaking of the graft in anterior cruciate ligament reconstruction. J ISAKOS 2022; 7: 94-98
- 67 Sailer MA, Skråmm I, Sivertsen EA. et al. Nationwide survey on the use of local antibiotics during anterior cruciate ligament reconstruction in Norway. Res Square 2020;
- 68 Yavuz IA, Oken OF, Yildirim AO. et al. No effect of vancomycin powder to prevent infection in primary total knee arthroplasty: a retrospective review of 976 cases. Knee Surg Sports Traumatol Arthrosc 2020; 28: 3055-3060
- 69 Lawrie CM, Kazarian GS, Barrack T. et al. Intra-articular administration of vancomycin and tobramycin during primary cementless total knee arthroplasty: determination of intra-articular and serum elution profiles. Bone Joint J 2021; 103-B: 1702-1708
- 70 Fleischman AN, Austin MS. Local intra-wound administration of powdered antibiotics in orthopaedic surgery. J Bone Jt Infect 2017; 2: 23-28
- 71 Pincher B, Fenton C, Jeyapalan R. et al. A systematic review of the single-stage treatment of chronic osteomyelitis. J Orthop Surg Res 2019; 14: 393
- 72 McNally MA, Ferguson JY, Lau AC. et al. Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/hydroxyapatite biocomposite: a prospective series of 100 cases. Bone Joint J 2016; 98-B: 1289-1296
- 73 Metsemakers WJ, Morgenstern M, Senneville E. et al. General treatment principles for fracture-related infection: recommendations from an international expert group. Arch Orthop Trauma Surg 2020; 140: 1013-1027
- 74 Metsemakers WJ, Fragomen AT, Moriarty TF. et al. Evidence-based recommendations for local antimicrobial strategies and dead space management in fracture-related infection. J Orthop Trauma 2020; 34: 18-29
- 75 Gramlich Y, Parvizi J. Enough is enough: salvage procedures in severe periprosthetic joint infection. Arthroplasty 2023; 5: 36
- 76 Tschudin-Sutter S, Frei R, Dangel M. et al. Validation of a treatment algorithm for orthopaedic implant-related infections with device-retention-results from a prospective observational cohort study. Clin Microbiol Infect 2016; 22: 457.e1-457.9
- 77 Kuiper JW, Willink RT, Moojen DJ. et al. Treatment of acute periprosthetic infections with prosthesis retention: review of current concepts. World J Orthop 2014; 5: 667-676
- 78 Sendi P, Lötscher PO, Kessler B. et al. Debridement and implant retention in the management of hip periprosthetic joint infection: outcomes following guided and rapid treatment at a single centre. Bone Joint J 2017; 99-B: 330-336
- 79 Ottesen CS, Troelsen A, Sandholdt H. et al. Acceptable success rate in patients with periprosthetic knee joint infection treated with debridement, antibiotics, and implant retention. J Arthroplasty 2019; 34: 365-368
- 80 Lora-Tamayo J, Senneville E, Ribera A. et al. The not-so-good prognosis of streptococcal periprosthetic joint infection managed by implant retention: the results of a large multicenter study. Clin Infect Dis 2017; 64: 1742-1752
- 81 Kapadia BH, Berg RA, Daley JA. et al. Periprosthetic joint infection. Lancet 2016; 387: 386-394
- 82 Wouthuyzen-Bakker M, Sebillotte M, Huotari K. et al. Lower success rate of débridement and implant retention in late acute versus early acute periprosthetic joint infection caused by Staphylococcus spp. results from a matched cohort study. Clin Orthop Relat Res 2020; 478: 1348-1355
- 83 Osmon D, Berbari E, Berendt A. et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2013; 56: e1-e25
- 84 Di Benedetto P, Di Benedetto ED, Salviato D. et al. Acute periprosthetic knee infection: is there still a role for DAIR?. Acta Biomed 2017; 88: 84-91
- 85 Argenson JN, Arndt M, Babis G. et al. Hip and knee section, treatment, debridement and retention of implant: proceedings of international consensus on orthopedic infections. J Arthroplasty 2019; 34 (Suppl. 02) S399-S419
- 86 Reinisch K, Schläppi M, Meier C. et al. Local antibiotic treatment with calcium sulfate as carrier material improves the outcome of debridement, antibiotics, and implant retention procedures for periprosthetic joint infections after hip arthroplasty – a retrospective study. J Bone Jt Infect 2022; 7: 11-21
- 87 de Vries L, van der Weegen W, Neve WC. et al. The effectiveness of debridement, antibiotics and irrigation for periprosthetic joint infections after primary hip and knee arthroplasty. A 15 years retrospective study in two community hospitals in the Netherlands. J Bone Jt Infect 2016; 1: 20-24
- 88 Fehring KA, Abdel MP, Ollivier M. et al. Repeat Two-Stage Exchange Arthroplasty for Periprosthetic Knee Infection Is Dependent on Host Grade. J Bone Joint Surg Am 2017; 99: 19-24
- 89 Metsemakers WJ, KuehlMoriarty TF. et al. Infection after fracture fixation: current surgical and microbiological concepts. Injury 2018; 49: 511-522
- 90 von Hasselbach C. Klinik und Pharmakokinetik von Kollagen-Gentamicin als adjuvante Lokaltherapie knöcherner Infektionen. Unfallchirurg 1989; 92: 459-470