Periprosthetic joint infection (PJI) following total hip and total knee arthroplasty continues to be a leading cause of re-operation and revision arthroplasty. Not only is the treatment of PJI notoriously challenging, but success rates are variable. Regardless of the surgical strategy used, successful management of PJI requires a comprehensive surgical debridement focused at eradicating the underlying biofilm followed by appropriate antimicrobial therapy. Although systemic antimicrobial delivery continues to be a cornerstone in the treatment of PJI, many surgeons have started using local antibiotics to deliver higher concentrations of antibiotics directly into the vulnerable joint and adjacent soft tissues, which often have compromised vascularity. Available evidence on the use of topical powder, bone cement, and calcium sulphate carriers for local delivery of antibiotics during the initial treatment of PJI is limited to studies that are extremely heterogeneous. There is currently no level-1 evidence to support routinely using these products. Further, appropriately powered, prospective studies are needed to quantify the safety and efficacy of antibiotic-located calcium-sulphate carriers to justify their added costs. These products should not encourage surgeons to deviate from best practice guidelines, such as those recommended during the International Consensus Meeting on Musculoskeletal Infections.
KohCKZengIRaviS, et al. Periprosthetic joint infection is the main cause of failure for modern knee arthroplasty: an analysis of 11,134 knees. Clin Orthop Relat Res2017; 475: 2194–2201.
2.
KamathAFOngKLLauE, et al. Quantifying the burden of revision total joint arthroplasty for periprosthetic infection. J Arthroplasty2015; 30: 1492–1497.
3.
LenguerrandEWhitehouseMRBeswickAD, et al. Risk factors associated with revision for prosthetic joint infection after hip replacement: a prospective observational cohort study. Lancet Infect Dis2018; 18: 1004–1014.
4.
Bourget-MurrayJBansalRSoroceanuA, et al. Assessment of risk factors for early-onset deep surgical site infection following primary total hip arthroplasty for osteoarthritis. J Bone Jt Infect2021; 6: 443–450.
5.
Bourget-MurrayJBansalRSoroceanuA, et al. Corrigendum to “Assessment of risk factors for early-onset deep surgical site infection following primary total hip arthroplasty for osteoarthritis” published in J. Bone Joint Infect., 6, 443-450, 2021. J Bone Jt Infect2022; 7: 151–153.
6.
KurtzSMLauEWatsonH, et al. Economic burden of periprosthetic joint infection in the United States. J Arthroplasty2012; 27(Suppl.): 61–65.e1.
7.
BozicKJKurtzSMLauE, et al. The epidemiology of revision total hip arthroplasty in the United States. J Bone Joint Surg Am2009; 91: 128–133.
8.
BozicKJKurtzSMLauE, et al. The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res2010; 468: 45–51.
9.
McMaster Arthroplasty Collaborative (MAC). Risk factors for periprosthetic joint infection following primary total hip arthroplasty: a 15-year, population-based cohort study. J Bone Joint Surg Am2020; 102: 503–509.
10.
Canadian Institute for Health Information. Early revisions of hip and knee replacements in Canada: a quality, productivity and capacity issue. Ottawa, ON: CIHI, 2020.
11.
SchwartzAMFarleyKXGuildGN, et al. Projections and epidemiology of revision hip and knee arthroplasty in the United States to 2030. J Arthroplasty2020; 35(Suppl.): S79–S85.
12.
ZmistowskiBKaramJADurinkaJB, et al. Periprosthetic joint infection increases the risk of one-year mortality. J Bone Joint Surg Am2013; 95: 2177–2184.
13.
HelwigPMorlockJOberstM, et al. Periprosthetic joint infection—effect on quality of life. Int Orthop2014; 38: 1077–1081.
14.
BoddapatiVFuMCMaymanDJ, et al. Revision total knee arthroplasty for periprosthetic joint infection is associated with increased postoperative morbidity and mortality relative to noninfectious revisions. J Arthroplasty2018; 33: 521–526.
15.
NicholsCIVoseJG. Clinical outcomes and costs within 90 days of primary or revision total joint arthroplasty. J Arthroplasty2016; 31: 1400–1406.e3.
16.
GundtoftPHPedersenABVarnumC, et al. Increased mortality after prosthetic joint infection in primary THA. Clin Orthop Relat Res2017; 475: 2623–2631.
17.
YaoJJHevesiMVisscherSL, et al. Direct inpatient medical costs of operative treatment of periprosthetic hip and knee infections are twofold higher than those of aseptic revisions. J Bone Joint Surg Am2021; 103: 312–318.
18.
PremkumarAKolinDAFarleyKX, et al. Projected economic burden of periprosthetic joint infection of the hip and knee in the United States. J Arthroplasty2021; 36: 1484–1489.e3.
19.
PeelTNDowseyMMBuisingKL, et al. Cost analysis of debridement and retention for management of prosthetic joint infection. Clin Microbiol Infect2013; 19: 181–186.
20.
KloucheSSarialiEMamoudyP. Total hip arthroplasty revision due to infection: a cost analysis approach. Orthop Traumatol Surg Res2010; 96: 124–132.
TriantafyllopoulosGKMemtsoudisSGZhangW, et al. Periprosthetic infection recurrence after 2-stage exchange arthroplasty: failure or fate?J Arthroplasty2017; 32: 526–531.
23.
TanTLGomezMMManriqueJ, et al. Positive culture during reimplantation increases the risk of subsequent failure in two-stage exchange arthroplasty. J Bone Joint Surg Am2016; 98: 1313–1319.
24.
KurtzSMLauECSonMS, et al. Are we winning or losing the battle with periprosthetic joint infection: trends in periprosthetic joint infection and mortality risk for the medicare population. J Arthroplasty2018; 33: 3238–3245.
25.
CullifordDMaskellJJudgeA, et al. Future projections of total hip and knee arthroplasty in the UK: results from the UK Clinical Practice Research Datalink. Osteoarthritis Cartilage2015; 23: 594–600.
26.
KurtzSMOngKLLauE, et al. Impact of the economic downturn on total joint replacement demand in the United States: updated projections to 2021. J Bone Joint Surg Am2014; 96: 624–630.
27.
NishitaniKSutipornpalangkulWde Mesy BentleyKL, et al. Quantifying the natural history of biofilm formation in vivo during the establishment of chronic implant-associated Staphylococcus aureus osteomyelitis in mice to identify critical pathogen and host factors. J Orthop Res2015; 33: 1311–1319.
28.
LovatiABBottagisioMde VecchiE, et al. Animal models of implant-related low-grade infections. A twenty-year review. Adv Exp Med Biol2017; 971: 29–50.
29.
VidlakDKielianT. Infectious dose dictates the host response during staphylococcus aureus orthopedic-implant biofilm infection. Infect Immun2016; 84: 1957–1965.
30.
KaplanJB. Antibiotic-induced biofilm formation. Int J Artif Organs2011; 34: 737–751.
31.
HøibyNCiofuOJohansenHK, et al. The clinical impact of bacterial biofilms. Int J Oral Sci2011; 3: 55–65.
32.
HøibyNBjarnsholtTGivskovM, et al. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents2010; 35: 322–332.
33.
ElkinsJMKatesSLangeJ, et al. General assembly, diagnosis, definitions: proceedings of international consensus on orthopedic infections. J Arthroplasty2019; 34(Suppl.): S181–S185.
34.
ZimmerliWTrampuzAOchsnerPE. Prosthetic-joint infections. N Engl J Med2004; 351: 1645–1654.
35.
ThakrarRRHorriatSKayaniB, et al. Indications for a single-stage exchange arthroplasty for chronic prosthetic joint infection: a systematic review. Bone Joint J2019; 101-B(Suppl. A): 19–24.
36.
RowanFEDonaldsonMJPietrzakJR, et al. The role of one-stage exchange for prosthetic joint infection. Curr Rev Musculoskelet Med2018; 11: 370–379.
37.
LeonardHALiddleADBurkeO, et al. Single- or two-stage revision for infected total hip arthroplasty? a systematic review of the literature. Clin Orthop Relat Res2014; 472: 1036–1042.
38.
FehringTKFehringKAHewlettA, et al. What’s new in musculoskeletal infection. J Bone Joint Surg Am2021; 103: 1251–1258.
39.
SlaneJGietmanBSquireM. Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin. J Orthop Res2018; 36: 1078–1085.
40.
HsiehP-HHuangK-CLeeP-C, et al. Two-stage revision of infected hip arthroplasty using an antibiotic-loaded spacer: retrospective comparison between short-term and prolonged antibiotic therapy. J Antimicrob Chemother2009; 64: 392–397.
41.
ButiniMECabricSTrampuzA, et al. In vitro anti-biofilm activity of a biphasic gentamicin-loaded calcium sulfate/hydroxyapatite bone graft substitute. Colloids Surf B Biointerfaces2018; 161: 252–260.
42.
DusaneDHDiamondSMKnechtCS, et al. Effects of loading concentration, blood and synovial fluid on antibiotic release and anti-biofilm activity of bone cement beads. J Control Release2017; 248: 24–32.
43.
CastanedaPMcLarenATavazivaG, et al. Biofilm antimicrobial susceptibility increases with antimicrobial exposure time. Clin Orthop Relat Res2016; 474: 1659–1664.
44.
AggarwalVKBakhshiHEckerNU, et al. Organism profile in periprosthetic joint infection: pathogens differ at two arthroplasty infection referral centers in Europe and in the United States. J Knee Surg2014; 27: 399–406.
45.
CoronaPSEspinalLRodríguez-PardoD, et al. Antibiotic susceptibility in gram-positive chronic joint arthroplasty infections: increased aminoglycoside resistance rate in patients with prior aminoglycoside-impregnated cement spacer use. J Arthroplasty2014; 29: 1617–1621.
46.
IarikovDDemianHRubinD, et al. Choice and doses of antibacterial agents for cement spacers in treatment of prosthetic joint infections: review of published studies. Clin Infect Dis2012; 55: 1474–1480.
47.
KiniSGGabrADasR, et al. Two-stage revision for periprosthetic hip and knee joint infections. Open Orthop J2016; 10: 579–588.
48.
LeekhaSTerrellCLEdsonRS. General principles of antimicrobial therapy. Mayo Clin Proc2011; 86: 156–167.
49.
OtteJEPolitiJRChambersB, et al. Intrawound vancomycin powder reduces early prosthetic joint infections in revision hip and knee arthroplasty. Surg Technol Int2017; 30: 284–289.
50.
RiesgoAMParkBKHerreroCP, et al. Vancomycin povidone-iodine protocol improves survivorship of periprosthetic joint infection treated with irrigation and debridement. J Arthroplasty2018; 33: 847–850.
51.
WinklerCDennisonJWooldridgeA, et al. Do local antibiotics reduce periprosthetic joint infections? a retrospective review of 744 cases. J Clin Orthop Trauma2018; 9(Suppl. 1): S34–S39.
52.
HeckmannNDMayfieldCKCulvernCN, et al. Systematic review and meta-analysis of intrawound vancomycin in total hip and total knee arthroplasty: a call for a prospective randomized trial. J Arthroplasty2019; 34: 1815–1822.
53.
JohnsonJDNesslerJMHorazdovskyRD, et al. Serum and wound vancomycin levels after intrawound administration in primary total joint arthroplasty. J Arthroplasty2017; 32: 924–928.
54.
SlullitelPADobranskyJSBaliK, et al. Is there a role for preclosure dilute betadine irrigation in the prevention of postoperative infection following total joint arthroplasty?J Arthroplasty2020; 35: 1374–1378.
55.
ChundamalaJWrightJG. The efficacy and risks of using povidone-iodine irrigation to prevent surgical site infection: an evidence-based review. Can J Surg2007; 50: 473–481.
56.
IorioRYuSAnoushiravaniAA, et al. Vancomycin powder and dilute povidone-iodine lavage for infection prophylaxis in high-risk total joint arthroplasty. J Arthroplasty2020; 35: 1933–1936.
57.
BuchalterDBTeoGMKirbyDJ, et al. Does the organism profile of periprosthetic joint infections change with a topical vancomycin powder and dilute povidone-iodine lavage protocol?J Arthroplasty2021; 36(Suppl.): S314–S319.
58.
QadirROchsnerJLChimentoGF, et al. Establishing a role for vancomycin powder application for prosthetic joint infection prevention-results of a wear simulation study. J Arthroplasty2014; 29: 1449–1456.
59.
SeebachEKubatzkyKF. Chronic implant-related bone infections-can immune modulation be a therapeutic strategy?Front Immunol2019; 10: 1724.
60.
RathboneCRCrossJDBrownKV, et al. Effect of various concentrations of antibiotics on osteogenic cell viability and activity. J Orthop Res2011; 29: 1070–1074.
61.
ShielsSMTennentDJLofgrenAL, et al. Topical rifampin powder for orthopaedic trauma part II: topical rifampin allows for spontaneous bone healing in sterile and contaminated wounds. J Orthop Res2018; 36: 3142–3150.
van de BeltHNeutDUgesDR, et al. Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials2000; 21: 1981–1987.
64.
SamuelSMathewBSVeeraraghavanB, et al. In vitro study of elution kinetics and bio-activity of meropenem-loaded acrylic bone cement. J Orthop Traumatol2012; 13: 131–136.
65.
GaspariniGDe GoriMCalonegoG, et al. Drug elution from high-dose antibiotic-loaded acrylic cement: a comparative, in vitro study. Orthopedics2014; 37: e999–e1005.
66.
VrabecGStevensonWElguizaouiS, et al. What is the intraarticular concentration of tobramycin using low-dose tobramycin bone cement in TKA: an in vivo analysis?Clin Orthop Relat Res2016; 474: 2441–2447.
67.
van VugtTAGArtsJJGeurtsJAP. Antibiotic-loaded polymethylmethacrylate beads and spacers in treatment of orthopedic infections and the role of biofilm formation. Front Microbiol2019; 10: 1626.
68.
TörholmCLidgrenLLindbergL, et al. Total hip joint arthroplasty with gentamicin-impregnated cement. A clinical study of gentamicin excretion kinetics. Clin Orthop Relat Res1983; 181: 99–106.
69.
WahligHDingeldeinE. Antibiotics and bone cements. Experimental and clinical long-term observations. Acta Orthop Scand1980; 51: 49–56.
70.
NeutDvan de BeltHvan HornJR, et al. Residual gentamicin-release from antibiotic-loaded polymethylmethacrylate beads after 5 years of implantation. Biomaterials2003; 24: 1829–1831.
71.
AnagnostakosKMeyerC. Antibiotic elution from hip and knee acrylic bone cement spacers: a systematic review. Biomed Res Int2017; 2017: 4657874.
72.
NeutDvan HornJRvan KootenTG, et al. Detection of biomaterial-associated infections in orthopaedic joint implants. Clin Orthop Relat Res2003; 413: 261–268.
73.
PreiningerBMatziolisGPfitznerT, et al. In situ tele-thermographic measurements during PMMA spacer augmentation in temporary arthrodesis after periprosthetic knee joint infection. Technol Health Care2012; 20: 337–341.
74.
WatanakunakornCTisoneJC. Synergism between vancomycin and gentamicin or tobramycin for methicillin-susceptible and methicillin-resistant staphylococcus aureus strains. Antimicrob Agents Chemother1982; 22: 903–905.
75.
DueyREChongACMcQueenDA, et al. Mechanical properties and elution characteristics of polymethylmethacrylate bone cement impregnated with antibiotics for various surface area and volume constructs. Iowa Orthop J2012; 32: 104–115.
76.
LautenschlagerEPJacobsJJMarshallGW, et al. Mechanical properties of bone cements containing large doses of antibiotic powders. J Biomed Mater Res1976; 10: 929–938.
77.
LautenschlagerEPMarshallGWMarksKE, et al. Mechanical strength of acrylic bone cements impregnated with antibiotics. J Biomed Mater Res1976; 10: 837–845.
78.
JamesALarsonT. Acute renal failure after high-dose antibiotic bone cement: case report and review of the literature. Ren Fail2015; 37: 1061–1066.
79.
SpringerBDLeeG-COsmonD, et al. Systemic safety of high-dose antibiotic-loaded cement spacers after resection of an infected total knee arthroplasty. Clin Orthop Relat Res2004; 427: 47–51.
80.
HsiehP-HChenL-HChenC-H, et al. Two-stage revision hip arthroplasty for infection with a custom-made, antibiotic-loaded, cement prosthesis as an interim spacer. J Trauma2004; 56: 1247–1252.
81.
DagneauxLLimbergAKOsmonDR, et al. Acute kidney injury when treating periprosthetic joint infections after total knee arthroplasties with antibiotic-loaded spacers: incidence, risks, and outcomes. J Bone Joint Surg Am2021; 103: 754–760.
82.
AbosalaAAliM. The use of calcium sulphate beads in periprosthetic joint infection, a systematic review. J Bone Jt Infect2020; 5: 43–49.
83.
EneRNicaMEneD, et al. Review of calcium-sulphate-based ceramics and synthetic bone substitutes used for antibiotic delivery in PJI and osteomyelitis treatment. EFORT Open Rev2021; 6: 297–304.
84.
CooperJJFloranceHMcKinnonJL, et al. Elution profiles of tobramycin and vancomycin from high-purity calcium sulphate beads incubated in a range of simulated body fluids. J Biomater Appl2016; 31: 357–365.
85.
McConougheySJHowlinRPWisemanJ, et al. Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites. J Biomed Mater Res B Appl Biomater2015; 103: 870–877.
86.
AikenSSCooperJJFloranceH, et al. Local release of antibiotics for surgical site infection management using high-purity calcium sulfate: an in vitro elution study. Surg Infect (Larchmt)2015; 16: 54–61.
87.
McPhersonEJDipaneMVSherifSM. Dissolvable antibiotic beads in treatment of periprosthetic joint infection and revision arthroplasty: the use of synthetic pure calcium sulfate (Stimulan) impregnated with vancomycin & tobramycin. Reconstructive Review2013; 3: 32–43.
88.
SakellariouVISavvidouOMarkopoulosC, et al. Combination of calcium hydroxyapatite antibiotic carrier with cement spacers in peri-prosthetic knee infections. Surg Infect (Larchmt)2015; 16: 748–754.
89.
KallalaRHaddadFS. Hypercalcaemia following the use of antibiotic-eluting absorbable calcium sulphate beads in revision arthroplasty for infection. Bone Joint J2015; 97-B: 1237–1241.
90.
LogolusoNDragoLGallazziE, et al. Calcium-based, antibiotic-loaded bone substitute as an implant coating: a pilot clinical study. J Bone Jt Infect2016; 1: 59–64.
91.
FlierlMACulpBMOkrojKT, et al. Poor outcomes of irrigation and debridement in acute periprosthetic joint infection with antibiotic-impregnated calcium sulfate beads. J Arthroplasty2017; 32: 2505–2507.
92.
KallalaRHarrisWEIbrahimM, et al. Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty: safety profile and complication rates. Bone Joint Res2018; 7: 570–579.
93.
LumZCPereiraGC. Local bio-absorbable antibiotic delivery in calcium sulfate beads in hip and knee arthroplasty. J Orthop2018; 15: 676–678.
94.
GramlichYWalterGKlugA, et al. Procedure for single-stage implant retention for chronic periprosthetic infection using topical degradable calcium-based antibiotics. Int Orthop2019; 43: 1559–1566.
95.
SandifordNA. Complication rates are low with the use of stimulan calcium sulphate based antibiotic delivery system in the management of patients with hip-related PJI: early results of a consecutive case series. Hip Int2020; 30(Suppl.): 3–6.
96.
CalannaFChenFRisitanoS, et al. Debridement, antibiotic pearls, and retention of the implant (DAPRI): a modified technique for implant retention in total knee arthroplasty PJI treatment. J Orthop Surg (Hong Kong)2019; 27: 2309499019874413.
97.
PiovanGFarinelliLScrepisD, et al. The role of antibiotic calcium sulfate beads in acute periprosthetic knee infection: a retrospective cohort study. Arthroplasty2022; 4: 42.
98.
TararMYKhalidAUsmanM, et al. Wound leakage with the use of calcium sulphate beads in prosthetic joint surgeries: a systematic review. Cureus2021; 13: e19650.
