Antibiotic Choice: The Synergistic Effect of Single vs Dual Antibiotics



      This review summarizes single vs dual antibiotic cement literature, evaluating for synergistic activity with dual antibiotics.


      A systematic review was performed for literature regarding dual antibiotics in cement, identifying 13 studies to include for review.


      Many in vitro studies reported higher elution from cement and/or improved bacteria inhibition with dual antibiotics, typically at higher dosages with a manual mixing technique. Limited clinical data from hip hemiarthroplasties and spacers demonstrated that dual antibiotics were associated with improved infection prevention and higher intra-articular antibiotic concentrations.


      In addition to broader pathogen coverage, several studies document synergy of elution and increased antibacterial activity when dual antibiotics are added to cement. Limited clinical evidence suggests that dual antibiotic cement may be associated with reduced infection rates.


      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 Journal of Arthroplasty
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Tansey R.
        • Mirza Y.
        • Sukeik M.
        • Shaath M.
        • Haddad F.S.
        Definition of periprosthetic hip and knee joint infections and the economic burden.
        Open Orthop J. 2016; 10: 662-668
        • Pulido L.
        • Ghanem E.
        • Joshi A.
        • Purtill J.J.
        • Parvizi J.
        Periprosthetic joint infection: the incidence, timing, and predisposing factors.
        Clin Orthop Relat Res. 2008; 466: 1710-1715
        • Chen A.F.
        • Parvizi J.
        Antibiotic-loaded bone cement and periprosthetic joint infection.
        J Long Term Eff Med Implants. 2014; 24: 89-97
        • Ajit Singh V.
        • Chun Haw B.
        • Haseeb A.
        • Shuan Ju Teh C.
        Hand-mixed vancomycin versus commercial tobramycin cement revisited: a study on mechanical and antibacterial properties.
        J Orthop Surg (Hong Kong). 2019; 27 (2309499019839616)
        • Moran E.
        • Masters S.
        • Berendt A.R.
        • McLardy-Smith P.
        • Byren I.
        • Atkins B.L.
        Guiding empirical antibiotic therapy in orthopaedics: the microbiology of prosthetic joint infection managed by debridement, irrigation and prosthesis retention.
        J Infect. 2007; 55: 1-7
        • Masri B.A.
        • Duncan C.P.
        • Beauchamp C.P.
        Long-term elution of antibiotics from bone-cement: an in vivo study using the prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) system.
        J Arthroplasty. 1998; 13: 331-338
        • Bertazzoni Minelli E.
        • Della Bora T.
        • Benini A.
        Different microbial biofilm formation on polymethylmethacrylate (PMMA) bone cement loaded with gentamicin and vancomycin.
        Anaerobe. 2011; 17: 380-383
        • Penner M.J.
        • Masri B.A.
        • Duncan C.P.
        Elution characteristics of vancomycin and tobramycin combined in acrylic bone-cement.
        J Arthroplasty. 1996; 11: 939-944
        • Slane J.
        • Gietman B.
        • Squire M.
        Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin.
        J Orthop Res. 2018; 36: 1078-1085
        • Sprowson A.P.
        • Jensen C.
        • Chambers S.
        • Parsons N.R.
        • Aradhyula N.M.
        • Carluke I.
        • et al.
        The use of high-dose dual-impregnated antibiotic-laden cement with hemiarthroplasty for the treatment of a fracture of the hip: The Fractured Hip Infection Trial.
        Bone Joint J. 2016; 98-B: 1534-1541
        • Savage P.
        • McCormick M.
        • Al-Dadah O.
        Arthroplasty infection rates in fractured neck of femur: single vs dual antibiotic cement.
        Ann R Coll Surg Engl. 2019; 101: 514-518
        • Salim S.A.
        • Everitt J.
        • Schwartz A.
        • Agarwal M.
        • Castenada J.
        • Fülöp T.
        • et al.
        Aminoglycoside impregnated cement spacer precipitating acute kidney injury requiring hemodialysis.
        Semin Dial. 2018; 31: 88-93
        • Walker L.C.
        • Baker P.
        • Holleyman R.
        • Deehan D.
        Microbial resistance related to antibiotic-loaded bone cement: a historical review.
        Knee Surg Sports Traumatol Arthrosc. 2017; 25: 3808-3817
        • Faschingbauer M.
        • Reichel H.
        • Bieger R.
        • Kappe T.
        Mechanical complications with one hundred and thirty eight (antibiotic-laden) cement spacers in the treatment of periprosthetic infection after total hip arthroplasty.
        Int Orthop. 2015; 39: 989-994
        • Trentinaglia M.T.
        • Van Der Straeten C.
        • Morelli I.
        • Logoluso N.
        • Drago L.
        • Romanò C.L.
        Economic evaluation of antibacterial coatings on healthcare costs in first year following total joint arthroplasty.
        J Arthroplasty. 2018; 33: 1656-1662
        • Hsieh P.-H.
        • Huang K.-C.
        • Tai C.-L.
        Liquid gentamicin in bone cement spacers: in vivo antibiotic release and systemic safety in two-stage revision of infected hip arthroplasty.
        J Trauma. 2009; 66: 804-808
        • Tyas B.
        • Marsh M.
        • Oswald T.
        • Refaie R.
        • Molyneux C.
        • Reed M.
        Antibiotic resistance profiles of deep surgical site infections in hip hemiarthroplasty; comparing low dose single antibiotic versus high dose dual antibiotic impregnated cement.
        J Bone Joint Infect. 2018; 3: 123-129
        • Li T.
        • Fu L.
        • Wang J.
        • Shi Z.
        High dose of vancomycin plus gentamicin incorporated acrylic bone cement decreased the elution of vancomycin.
        Infect Drug Resist. 2019; 12: 2191-2199
        • Frew N.M.
        • Cannon T.
        • Nichol T.
        • Smith T.J.
        • Stockley I.
        Comparison of the elution properties of commercially available gentamicin and bone cement containing vancomycin with “home-made” preparations.
        Bone Joint J. 2017; 99-B: 73-77
        • Klekamp J.
        • Dawson J.M.
        • Haas D.W.
        • DeBoer D.
        • Christie M.
        The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty.
        J Arthroplasty. 1999; 14: 339-346
        • Boelch S.P.
        • Jordan M.C.
        • Arnholdt J.
        • Rudert M.
        • Luedemann M.
        • Steinert A.F.
        Loading with vancomycin does not decrease gentamicin elution in gentamicin premixed bone cement.
        J Mater Sci Mater Med. 2017; 28: 104
        • Cerretani D.
        • Giorgi G.
        • Fornara P.
        • Bocchi L.
        • Neri L.
        • Ceffa R.
        • et al.
        The in vitro elution characteristics of vancomycin combined with imipenem-cilastatin in acrylic bone-cements: a pharmacokinetic study.
        J Arthroplasty. 2002; 17: 619-626
        • Martínez-Moreno J.
        • Merino V.
        • Nácher A.
        • Rodrigo J.L.
        • Bonet Yuste B.B.
        • Merino-Sanjuán M.
        Bioactivity of ceftazidime and fluconazole included in polymethyl methacrylate bone cement for use in arthroplasty.
        J Arthroplasty. 2017; 32: 3126-3133.e1