Single-stage revision of MRSA orthopedic device-related infection in sheep with an antibiotic-loaded hydrogel.
Animals
Anti-Bacterial Agents
/ administration & dosage
Biofilms
/ drug effects
Bone Cements
Drug Evaluation, Preclinical
Gentamicins
/ administration & dosage
Hydrogels
Methicillin-Resistant Staphylococcus aureus
Polymethyl Methacrylate
Prosthesis-Related Infections
/ drug therapy
Reoperation
/ adverse effects
Sheep
Staphylococcal Infections
/ drug therapy
Vancomycin
/ administration & dosage
MRSA
fracture-related infection
hydrogel
local antibiotics
orthopaedic device-related infection
peri-prosthetic joint infection
single-stage revision
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
01
09
2020
revised:
04
12
2020
accepted:
07
12
2020
pubmed:
12
12
2020
medline:
1
5
2021
entrez:
11
12
2020
Statut:
ppublish
Résumé
Local antimicrobial therapy is an integral aspect of treating orthopedic device-related infection (ODRI), which is conventionally administered via polymethyl-methacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibiotic-loaded hydrogel in a single-stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture-negative. Antibiotic delivery via hydrogel resulted in 10-100 times greater local concentrations for the first 2-3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.
Substances chimiques
Anti-Bacterial Agents
0
Bone Cements
0
Gentamicins
0
Hydrogels
0
Vancomycin
6Q205EH1VU
Polymethyl Methacrylate
9011-14-7
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
438-448Informations de copyright
© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.
Références
Czaja AS, Rivara FP, Wang J, et al. Late outcomes of trauma patients with infections during index hospitalization. J Trauma. 2009;67:805-814.
Metsemakers W-J, Smeets B, Nijs S, Hoekstra H. Infection after fracture fixation of the tibia: analysis of healthcare utilization and related costs. Injury. 2017;48:1204-1210.
Metsemakers W-J, Fragomen AT, Moriarty TF, et al. Evidence-based recommendations for local antimicrobial strategies and dead space management in fracture-related infection. J Orthop Trauma. 2019;34(1):18-29.
Hake ME, Young H, Hak DJ, Stahel PF, Hammerberg EM, Mauffrey C. Local antibiotic therapy strategies in orthopaedic trauma: practical tips and tricks and review of the literature. Injury. 2015;46:1446-1456.
Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with Palacos resins. Chirurg. 1970;41:511.
Hovelius L, Josefsson G. An alternative method for exchange operation of infected arthroplasty. Acta Orthop Scand. 1979;50:93-96.
Conway J, Mansour J, Kotze K, Specht S, Shabtai L. Antibiotic cement-coated rods: an effective treatment for infected long bones and prosthetic joint nonunions. Bone Joint J. 2014;96-b:1349-1354.
Parry MC, Duncan CP. The challenge of methicillin resistant staphylococcal infection after total hip replacement: overlooked or overstated? Bone Joint J. 2014;96:60-65.
Mortazavi SMJ, Vegari D, Ho A, Zmistowski B, Parvizi J. Two-stage exchange arthroplasty for infected total knee arthroplasty: predictors of failure. Clin Orthop Relat Res. 2011;469:3049-3054.
Kilgus D, Howe D, Strang A. Results of periprosthetic hip and knee infections caused by resistant bacteria. Clin Orthop Relat Res. 2002;404:116-124.
Morgenstern M, Erichsen C, Militz M, et al. The AO trauma CPP bone infection registry: epidemiology and outcomes of Staphylococcus aureus bone infection. J Orthop Res. 2020;39(1):136-146.
Belt HD, Neut D, Schenk W, Horn JR, Mei HCD, Busscher HJ. Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation. Acta Orthop Scand. 2000;71:625-629.
Neut D. Biomaterial-associated infection of gentamicin-loaded PMMA beads in orthopaedic revision surgery. J Antimicrob Chemother. 2001;47:885-891.
Inzana J, Trombetta R, Schwarz E, Kates S, Awad H. 3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection. Eur Cell Mater. 2015;30:232-247.
Pelletier MH, Malisano L, Smitham PJ, Okamoto K, Walsh WR. The compressive properties of bone cements containing large doses of antibiotics. J Arthroplasty. 2009;24:454-460.
Foster AL, Moriarty TF, Trampuz A, et al. Fracture-related infection: current methods for prevention and treatment. Expert Rev Anti Infect Ther. 2020;18:1-15.
Kunutsor SK, Whitehouse MR, Blom AW, Beswick AD. Re-infection outcomes following one- and two-stage surgical revision of infected hip prosthesis: a systematic review and meta-analysis. PLOS One. 2015;10:e0139166.
Kunutsor SK, Whitehouse MR, Lenguerrand E, Blom AW, Beswick AD. Re-infection outcomes following one- and two-stage surgical revision of infected knee prosthesis: a systematic review and meta-analysis. PLOS One. 2016;11:e0151537.
Gehrke T, Zahar A, Kendoff D. One-stage exchange: it all began here. Bone Joint J. 2013;95:77-83.
Prasarn ML, Ahn J, Achor T, Matuszewski P, Lorich DG, Helfet DL. Management of infected femoral nonunions with a single-staged protocol utilizing internal fixation. Injury. 2009;40:1220-1225.
D'este M, Alini M, Eglin D. Single step synthesis and characterization of thermoresponsive hyaluronan hydrogels. Carbohydr Polymers. 2012;90:1378-1385.
Ter Boo G-JA, Arens D, Metsemakers W-J, et al. Injectable gentamicin-loaded thermo-responsive hyaluronic acid derivative prevents infection in a rabbit model. Acta Biomater. 2016;43:185-194.
Malizos K, Blauth M, Danita A, et al. Fast-resorbable antibiotic-loaded hydrogel coating to reduce post-surgical infection after internal osteosynthesis: a multicenter randomized controlled trial. J Orthop Traumatol. 2017;18:159-169.
Capuano N, Logoluso N, Gallazzi E, Drago L, Romanò CL. One-stage exchange with antibacterial hydrogel coated implants provides similar results to two-stage revision, without the coating, for the treatment of peri-prosthetic infection. Knee Surg Sports Traumatol Arthrosc. 2018;26:3362-3367.
Boot W, Foster A, Schmid T, et al. 2019. Antibiotic-loaded hydrogel outperforms gold-standard treatment in a large animal model of MRSA implant-associated osteomyelitis. In: 38th Annual Meeting of the European Bone and Joint Infection Society. Antwerp, Belgium.
Moriarty T, Schmid T, Post V, et al. A large animal model for a failed two-stage revision of intramedullary nail-related infection by methicillin-resistant Staphylococcus aureus. Eur Cell Mater. 2017;34:83-98.
Moriarty TF, Harris LG, Mooney RA, et al. Recommendations for design and conduct of preclinical in vivo studies of orthopedic device-related infection. J Orthop Res. 2019;37:271-287.
Depypere M, Kuehl R, Metsemakers W-J, et al. Recommendations for antimicrobial therapy in fracture-related infection: a consensus from an international expert group. J Orthop Trauma. 2019;34(1):30-41.
Osmon DR, Berbari EF, Berendt AR, et al. Executive summary: diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013;56:1-10.
Stevens CM, Tetsworth KD, Calhoun JH, Mader JT. An articulated antibiotic spacer used for infected total knee arthroplasty: a comparative in vitro elution study of Simplex ® and Palacos ® bone cements. J Orthop Res. 2005;23:27-33.
Kanakaris N, Gudipati S, Tosounidis T, Harwood P, Britten S, Giannoudis PV. The treatment of intramedullary osteomyelitis of the femur and tibia using the Reamer-Irrigator-Aspirator system and antibiotic cement rods. Bone Joint J. 2014;96:783-788.
Kummer A, Tafin UF, Borens O. Effect of sonication on the elution of antibiotics from polymethyl methacrylate (PMMA). J Bone Jt Infect. 2017;2:208-212.
Post V, Wahl P, Richards RG, Moriarty TF. Vancomycin displays time-dependent eradication of mature Staphylococcus aureus biofilms. J Orthop Res. 2017;35:381-388.
de Mesy Bentley KL, Trombetta R, Nishitani K, et al. Evidence of Staphylococcus aureus deformation, proliferation, and migration in canaliculi of live cortical bone in murine models of osteomyelitis. J Bone Miner Res. 2017;32:985-990.
ter Boo GJ, Schmid T, Zderic I, et al. Local application of a gentamicin-loaded thermo-responsive hydrogel allows for fracture healing upon clearance of a high Staphylococcus aureus load in a rabbit model. Eur Cell Mater. 2018;35:151-164.
Rittmann WW, Perren SM 1975. Cortical Bone Healing After Internal Fixation and Infection: Biomechanics and Biology. Springer-Verlag.
Foster AL, Moriarty TF, Zalavras C, et al. The influence of biomechanical stability on bone healing and fracture-related infection: the legacy of Stephan Perren. Injury. 2020.
Rathbone CR, Cross JD, Brown KV, Murray CK, Wenke JC. Effect of various concentrations of antibiotics on osteogenic cell viability and activity. J Orthop Res. 2011;29:1070-1074.
Rowan FE, Donaldson MJ, Pietrzak JR, Haddad FS. The role of one-stage exchange for prosthetic joint infection. Curr Rev Musculoskelet Med. 2018;11:370-379.
Wolf CF, Gu NY, Doctor JN, Manner PA, Leopold SS. Comparison of one and two-stage revision of total hip arthroplasty complicated by infection: a Markov expected-utility decision analysis. J Bone Joint Surg Am. 2011;93:631-639.
Busscher HJ, Alt V, Van Der Mei HC, et al. A trans-atlantic perspective on stagnation in clinical translation of antimicrobial strategies for the control of biomaterial-implant-associated infection. ACS Biomater Sci Eng. 2019;5:402-406.
Moriarty TF, Grainger DW, Richards RG. Challenges in linking preclinical anti-microbial research strategies with clinical outcomes for device-associated infections. Eur Cells Mater. 2014;28:112-128.