Research Article| Volume 40, P63-70, January 2023

Download started.


Low dose vancomycin-loaded spacers for two-stage revision knee arthroplasty: High success, low toxicity

Published:November 18, 2022DOI:



      Two-stage revision arthroplasty is a widely used treatment method for infected knee arthroplasty. Loading high doses of antibiotics to spacer during the first stage is standard practice. However, there are reported systemic side effects attributed to antibiotic-loaded spacers. The aim of our study is to investigate the success rate and systemic toxicity following the first stage revision knee arthroplasty with low-dose vancomycin-loaded spacers.


      We included patients with infected knee arthroplasty eligible for two-stage revision arthroplasty from 2001 to 2020. One gram of vancomycin is added per pack of bone cement. Spacers were handmade in the operating theatre. Following the first stage, pre-operative and postoperative culture results, infection parameters, kidney and liver function tests, and functional scores were analyzed. Kaplan-Meier survival analysis was done to determine the success rate.


      Fifty patients with a mean follow-up of 48 months (24–108) were included in the study. A five-year survival analysis showed an 88.5% success rate. Fourteen percent of the patients had acute kidney injury with creatinine levels between 1.12–2.80 mg/dl, and 8% had a mild drug-induced liver injury with elevated serum ALT levels between 223–540 U/L and total bilirubin levels between 0.59–1.23 mg/dl. None of the patients required dialysis. All of the systemic side effects were reversible.


      Our results have suggested that low dose antibiotic-loaded spacers are comparable to the studies with high dose antibiotic loaded spacers regarding infection eradication and survival rates. They are less likely to cause severe systemic side effects. Therefore we suggest low dose antibiotic-loaded spacers should be considered when treating patients with vancomycin sensitive Staphylococcal species and culture negative infected knee arthroplasty.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The Knee
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Goldman R.T.
        • Scuderi G.R.
        • Insall J.N.
        2-stage reimplantation for infected total knee replacement.
        Clin Orthop Relat Res. 1996; 331: 118-124
        • Gusso M.I.
        • Capone A.
        • Civinini R.
        • Scoccianti G.
        The spacer block technique in revision of total knee arthroplasty with septic loosening.
        La Chirurgia degli organi di movimento. 1995; 80: 21-27
        • Insall J.N.
        • Thompson F.M.
        • Brause B.D.
        Two-stage reimplantation for the salvage of infected total knee arthroplasty.
        J Bone Joint Surg Am. 1983; 65: 1087-1098
        • Windsor R.E.
        • Insall J.N.
        • Urs W.K.
        • Miller D.V.
        • Brause B.D.
        Two-stage reimplantation for the salvage of total knee arthroplasty complicated by infection. Further follow-up and refinement of indications.
        J Bone Joint Surg Am. 1990; 72: 272-278
        • Anagnostakos K.
        Therapeutic Use of Antibiotic-loaded Bone Cement in the Treatment of Hip and Knee Joint Infections.
        J Bone Jt Infect. 2017; 2: 29-37
        • Fink B.
        • Vogt S.
        • Reinsch M.
        • Buchner H.
        Sufficient release of antibiotic by a spacer 6 weeks after implantation in two-stage revision of infected hip prostheses.
        Clin Orthop Relat Res. 2011; 469: 3141-3147
        • Hsieh P.H.
        • Chang Y.H.
        • Chen S.H.
        • Ueng S.W.
        • Shih C.H.
        High concentration and bioactivity of vancomycin and aztreonam eluted from Simplex cement spacers in two-stage revision of infected hip implants: a study of 46 patients at an average follow-up of 107 days.
        J Orthop Res. 2006; 24: 1615-1621
        • Dagneaux L.
        • Limberg A.K.
        • Osmon D.R.
        • Leung N.
        • Berry D.J.
        • Abdel M.P.
        Acute kidney injury when treating periprosthetic joint infections after total knee arthroplasties with antibiotic-loaded spacers: incidence, risks, and outcomes.
        J Bone Joint Surg Am. 2021; 103: 754-760
        • Curtis J.M.
        • Sternhagen V.
        • Batts D.
        Acute renal failure after placement of tobramycin-impregnated bone cement in an infected total knee arthroplasty.
        Pharmacotherapy. 2005; 25: 876-880
        • Dovas S.
        • Liakopoulos V.
        • Papatheodorou L.
        • Chronopoulou I.
        • Papavasiliou V.
        • Atmatzidis E.
        • et al.
        Acute renal failure after antibiotic-impregnated bone cement treatment of an infected total knee arthroplasty.
        Clin Nephrol. 2008; 69: 207-212
        • van Raaij T.M.
        • Visser L.E.
        • Vulto A.G.
        • Verhaar J.A.
        Acute renal failure after local gentamicin treatment in an infected total knee arthroplasty.
        J Arthroplasty. 2002; 17: 948-950
        • Marczak D.
        • Synder M.
        • Sibinski M.
        • Polguj M.
        • Dudka J.
        • Kowalczewski J.
        Two stage revision hip arthroplasty in periprosthetic joint infection. Comparison study: with or without the use of a spacer.
        Int Orthop. 2017; 41: 2253-2258
        • Hsieh P.H.
        • Shih C.H.
        • Chang Y.H.
        • Lee M.S.
        • Shih H.N.
        • Yang W.E.
        Two-stage revision hip arthroplasty for infection: comparison between the interim use of antibiotic-loaded cement beads and a spacer prosthesis.
        J Bone Joint Surg Am. 2004; 86: 1989-1997
        • Jahoda D.
        • Sosna A.
        • Landor I.
        • Vavrik P.
        • Pokorny D.
        • Hudec T.
        Two-stage reimplantation using spacers–the method of choice in treatment of hip joint prosthesis-related infections. Comparison with methods used from 1979 to 1998.
        Acta Chir Orthop Traumatol Cech. 2003; 70: 17-24
        • Caglar O.
        • Tokgozoglu M.
        • Akgun R.C.
        • Atilla B.
        Low-dose vancomycin-loaded cement spacer for two-stage revision of infected total hip arthroplasty.
        Jt Dis Relat Surg. 2020; 31: 449-455
        • Ting N.T.
        • Della Valle C.J.
        Diagnosis of periprosthetic joint infection-an algorithm-based approach.
        J Arthroplasty. 2017; 32: 2047-2050
        • Ronco C.
        • Bellomo R.
        • Kellum J.A.
        Acute kidney injury.
        Lancet. 2019; 394: 1949-1964
        • Aithal G.P.
        • Watkins P.B.
        • Andrade R.J.
        • Larrey D.
        • Molokhia M.
        • Takikawa H.
        • et al.
        Case definition and phenotype standardization in drug-induced liver injury.
        Clin Pharmacol Ther. 2011; 89: 806-815
        • Sharkey P.F.
        • Lichstein P.M.
        • Shen C.
        • Tokarski A.T.
        • Parvizi J.
        Why are total knee arthroplasties failing today–has anything changed after 10 years?.
        J Arthroplasty. 2014; 29: 1774-1778
        • Pangaud C.
        • Ollivier M.
        • Argenson J.N.
        Outcome of single-stage versus two-stage exchange for revision knee arthroplasty for chronic periprosthetic infection.
        EFORT Open Rev. 2019; 4: 495-502
        • Petis S.M.
        • Perry K.I.
        • Mabry T.M.
        • Hanssen A.D.
        • Berry D.J.
        • Abdel M.P.
        Two-stage exchange protocol for periprosthetic joint infection following total knee arthroplasty in 245 knees without prior treatment for infection.
        J Bone Joint Surg Am. 2019; 101: 239-249
        • Yusuf E.
        • Croughs P.
        Vancomycin prophylaxis in prosthetic joint surgery?.
        Clin Microbiol Infect. 2020; 26: 3-5
        • Cabrita H.B.
        • Croci A.T.
        • Camargo O.P.
        • Lima A.L.
        Prospective study of the treatment of infected hip arthroplasties with or without the use of an antibiotic-loaded cement spacer.
        Clinics (Sao Paulo). 2007; 62: 99-108
        • Corona P.S.
        • Barro V.
        • Mendez M.
        • Caceres E.
        • Flores X.
        Industrially prefabricated cement spacers: do vancomycin- and gentamicin-impregnated spacers offer any advantage?.
        Clin Orthop Relat Res. 2014; 472: 923-932
        • Guray B.A.
        • Atilla B.
        Effect of low-dose vancomycin, gentamycin and boric acid containing bone cement on bacteria cultured from periprosthetic joint infection patients.
        Orthopaedics and Traumatology. Hacettepe University Faculty of Medicine, Ankara2012
        • Bishop A.R.
        • Kim S.
        • Squire M.W.
        • Rose W.E.
        • Ploeg H.L.
        Vancomycin elution, activity and impact on mechanical properties when added to orthopedic bone cement.
        J Mech Behav Biomed Mater. 2018; 87: 80-86
        • Edelstein A.I.
        • Okroj K.T.
        • Rogers T.
        • Della Valle C.J.
        • Sporer S.M.
        Systemic absorption of antibiotics from antibiotic-loaded cement spacers for the treatment of periprosthetic joint infection.
        J Arthroplasty. 2018; 33: 835-839
        • Koo K.H.
        • Yang J.W.
        • Cho S.H.
        • Song H.R.
        • Park H.B.
        • Ha Y.C.
        • et al.
        Impregnation of vancomycin, gentamicin, and cefotaxime in a cement spacer for two-stage cementless reconstruction in infected total hip arthroplasty.
        J Arthroplasty. 2001; 16: 882-892
        • Parvizi J.
        • Tan T.L.
        • Goswami K.
        • Higuera C.
        • Della Valle C.
        • Chen A.F.
        • et al.
        The 2018 definition of periprosthetic hip and knee infection: an evidence-based and validated criteria.
        J Arthroplasty. 2018; 33: 1309-14 e2
        • Preobrazhensky P.
        • Bozhkova S.
        • Kochish A.
        • Tikhilov R.
        • Kazemirsky A.
        Comparative analysis of pathogen structure in patients with PJI after primary total hip and knee arthroplasty.
        Arch Orthop Trauma Surg. 2021; 141: 1963-1969
        • Ludwick L.
        • Chisari E.
        • Wang J.
        • Clarkson S.
        • Collins L.
        • Parvizi J.
        Emergence of antibiotic resistance across two-stage revision for periprosthetic joint infection.
        J Arthroplasty. 2021; 36: 2946-2950
        • Jiang Q.
        • Fu J.
        • Chai W.
        • Hao L.B.
        • Zhou Y.G.
        • Xu C.
        • et al.
        Two-stage exchange Arthroplasty is a viable treatment for Periprosthetic joint infection in inflammatory diseases.
        BMC Musculoskelet Disord. 2020; 21: 681