Surgical site infection (SSI) presents a ubiquitous concern to surgical specialties, especially in the presence of prosthetic material. Antibiotic-impregnated beads present a novel and evolving means to combat this condition. This review aims to analyze the quality of evidence and methods of antibiotic bead use, particularly for application within vascular surgery.
Methods:
A systematic scoping review was conducted within Embase, MEDLINE, and the Cochrane Registry of Randomized Controlled Trials. Articles were evaluated by 2 independent reviewers. Level of evidence was evaluated using the Oxford Center for Evidence-Based Medicine Criteria and the Cochrane Risk of Bias Tool for Randomized Controlled Trials.
Results:
The search yielded 6951 papers, with 275 included for final analysis. Publications increased in frequency from 1978 to the present. The most common formulation was polymethyl methacrylate; however publications on biodegradable formulations, including calcium sulfate beads, have been published with increasing frequency. Most publications had positive conclusions (94.2%); however, the data was mainly subjective and may be prone to publication bias. Only 11 randomized controlled trials were identified and all but one was evaluated to be at a high risk of bias. The most common indication was for osteomyelitis (52%), orthopedic prosthetic infections (20%), and trauma (9%). Within vascular surgery, beads have been used primarily for the treatment of graft infection, with freedom from recurrence rates being reported from 41% to 87.5%.
Conclusions:
Antibiotic-impregnated beads provide a means to deliver high doses of antibiotic directly to a surgical site, without the risks of parenteral therapy. There has yet to be significant high-level quality data published on their use. There is a large body of evidence that suggests antibiotic beads may be used in SSIs in high-risk patients, prosthetic infections, and other complex surgical infections. Important potential areas of application in vascular surgery include graft infection, prevention of wound infection in high-risk patients, and diabetic foot infection.
AndersonDJKayeKSClassenD, et al.Strategies to prevent surgical site infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29(S1):S51–S61. doi:10.1086/591064
2.
HenrySLOstermannPAWSeligsonD. The prophylactic use of antibiotic impregnated beads in open fractures. J Trauma Acute Care Surg. 1990;30(10):1231–1238.
3.
CarverDCKuehnSBWeinleinJC. Role of systemic and local antibiotics in the treatment of open fractures. Orthop Clin North Am. 2017;48(2):137–153.
4.
DavisFMSutzkoDCGreySF, et al.Predictors of surgical site infection after open lower extremity revascularization. J Vasc Surg. 2017;65(6):1769–1778.e3. doi:10.1016/j.jvs.2016.11.053
5.
FischerJPNelsonJARohrbachJI, et al.Prophylactic muscle flaps in vascular surgery: the Penn Groin Assessment Scale. Plast Reconstr Surg. 2012;129(6):940e–949e. doi:10.1097/PRS.0b013e31824ecb17.
6.
DesaiSDuaAPatelB, et al.Surgical site infections after lower extremity revascularization procedures involving groin incisions. Ann Vasc Surg. 2014;28(1):53–58.
7.
Berriós-TorresSIUmscheidCABratzlerDW, et al.Centers for disease control and prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg. 2017;152(8):784–791. doi:10.1001/jamasurg.2017.0904
8.
HuirasPLoganJKPapadopoulosSWhitneyD. Local antimicrobial administration for prophylaxis of surgical site infections. Pharmacother J Hum Pharmacol Drug Ther. 2012;32(11):1006–1019.
9.
WahligHDingeldeinEBergmannRReussK. The release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacokinetic study. J Bone Joint Surg Br. 1978;60(2):270–275.
10.
OstermannPAHenrySLSeligsonD. The role of local antibiotic therapy in the management of compound fractures. Clin Orthop Relat Res. 1993;295:102–111.
11.
WhiteTLCullifordATZomayaMFreedGDemasCP. Use of antibiotic-impregnated absorbable beads and tissue coverage of complex wounds. Am Surg. 2016;82(11):1068–1072.
12.
SørensenTSSørensen llanIMerserS. Rapid release of gentamicin from collagen sponge: in vitro comparison with plastic beads. Acta Orthop Scand. 1990;61(4):353–356.
13.
McConougheySJHowlinRPWisemanJStoodleyPCalhounJH. Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites. J Biomed Mater Res—Part B Appl Biomater. 2015;103(4):870–877. doi:10.1002/jbm.b.33247
14.
BeckerPLSmithRAWilliamsRSDutkowskyJP. Comparison of antibiotic release from polymethylmethacrylate beads and sponge collagen. J Orthop Res. 1994;12(5):737–741. doi:10.1002/jor.1100120517
15.
McKeeMDLi-BlandEAWildLMSchemitschEH. A prospective, randomized clinical trial comparing an antibiotic-impregnated bioabsorbable bone substitute with standard antibiotic-impregnated cement beads in the treatment of chronic osteomyelitis and infected nonunion. J Orthop Trauma. 2010;24(8):483–490. doi:10.1097/BOT.0b013e3181df91d9
16.
PetersMDJGodfreyCMKhalilHMcInerneyPParkerDSoaresCB. Guidance for conducting systematic scoping reviews. Int J Evid Based Healthc. 2015;13(3):141–146.
17.
HowickJChalmersIGlasziouP, et al.Explanation of the 2011 oxford centre for evidence-based medicine (OCEBM) levels of evidence (background document). Oxford Cent Evidence-Based Med. 2011. https://www.cebm.net/2016/05/ocebm-levels-of-evidence/
18.
HigginsJPTAltmanDGGøtzschePC, et al.The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
19.
ChanYUengSWWangCLeeSChenC. Is an effective and safe method for the management of small infected tibial defects: a comparison study. Crit Care. 2000;48(2):246–255.
20.
BlahaJDCalhounJHNelsonCL, 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. doi:10.1097/00003086-199310000-00003
21.
CalhounJHAngerDMLedbetterBRCobosJAMaderJT. The Ilizarov fixator and polymethylmethacrylate-antibiotic beads for the treatment of infected deformities. Clin Orthop Relat Res. 1993;(295):13–22.
22.
CalhounJHHenrySLAngerDMCobosJAMaderJT. The treatment of infected nonunions with gentamicin-polymethylmethacrylate antibiotic beads. Clin Orthop Relat Res. 1993;(295):23–27.
23.
HaydonRCBlahaJDMancinelliCKoikeK. Audiometric thresholds in osteomyelitis patients treated with gentamicin-impregnated methylmethacrylate beads (septopal). Clin Orthop Relat Res. 1993;(295):43–46. doi:10.1097/00003086-199310000-00008
24.
NelsonCLEvansRPBlahaJDCalhounJHenrySLPatzakisMJ. A comparison of gentamicin-impregnated polymethylmethacrylate bead implantation to conventional parenteral antibiotic therapy in infected total hip and knee arthroplasty. Clin Orthop Relat Res. 1993;(295):96–101.
25.
HedstromSALidgrenLTörholmCÖnnerfältR. Antibiotic containing bone cement beads in the treatment of deep muscle and skeletal infections. Acta Orthop. 1980;51(1-6):863–869. doi:10.3109/17453678008990886
26.
MoehringHGravelCChapmanMOlsonS. Comparison of antibiotic beads and intravenous antibiotics in open fractures. Clin Orthop Relat Res. 2000;372(372):254–261.
27.
RosenHRMarczellAPCzerwenkaEStiererMOSpoulaHWaslH. Local gentamicin application for perineal wound healing following abdominoperineal rectum excision. Am J Surg. 1991;162(5):438–441.
28.
JuyalAKhuranaGMaheshwariR. Red man syndrome: an unusual complication of vancomycin beads. Bangladesh J Med Sci. 2015;14(3):290–291. doi:10.3329/bjms.v14i3.17955
29.
SongEKSeonJKJeongMS. Delayed-type hypersensitivity reaction to piperacillin/tazobactam in a patient with an infected total knee replacement. J Bone Joint Surg Br. 2010;92-B(11):1596–1599. doi:10.1302/0301-620X.92B11.24827
30.
GordonPMWhiteMIScotlandTR. Generalized sensitivity from an implanted orthopaedic antibiotic minichain containing nickel. Contact Dermatitis. 1994;30(3):181–182.
31.
CresswellTShahaneSStockleyI. Irreducible dislocation of a hip total prosthesis: the risk of gentamicin beads. Orthopedics. 2000;23(10):1095–1096.
32.
FiddianNSudlowRBrowettJ. Ruptured femoral vein. A complication of the use of gentamicin beads in an infected excision arthroplasty of the hip. J Bone Joint Surg Br. 1984;66(4):493–494.
NeutD. Biomaterial-associated infection of gentamicin-loaded PMMA beads in orthopaedic revision surgery. J Antimicrob Chemother. 2001;47(6):885–891. doi:10.1093/jac/47.6.885
35.
KallalaRHaddadFS. Hypercalcaemia following the use of antibiotic-eluting absorbable calcium sulphate beads in revision arthroplasty for infection. Bone Joint J. 2015;97-B(9):1237–1241. doi:10.1302/0301-620X.97B9.34532
36.
Van RaaijTMVisserLEVultoAGVerhaarJAN. Acute renal failure after local gentamicin treatment in an infected total knee arthroplasty. J Arthroplasty. 2002;17(7):948–950. doi:10.1054/arth.2002.34525
37.
De KlaverPAGDe KoningJJanssenRPADerijksLJJ. High systemic gentamicin levels and ototoxicity after implantation of gentamicin beads in a 70-year-old mana case report. Acta Orthop. 2009;80(6):734–736. doi:10.3109/17453670903487032
38.
De KlaverPAGHendriksJGEVan OnzenoortHAWSchreursBWTouwDJDerijksLJJ. Gentamicin serum concentrations in patients with gentamicin-PMMA beads for infected hip joints: a prospective observational cohort study. Ther Drug Monit. 2012;34(1):67–71. doi:10.1097/FTD.0b013e31823d7b89
39.
EckmanJBHenrySLMaginoPDSeligsonD. Wound and serum levels of tobramycin with the prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures. Clin Orthop Relat Res. 1988;(237):213–215. doi:10.1097/00003086-198812000-00031
40.
SalvatiECallaghanJBrauseBKleinRSmallR. Reimplantation in infection. Elution of gentamicin from cement and beads. Clin Orthop Relat Res. 1986;(207):83–93.
41.
LivioFWahlPCsajkaCGautierEBuclinT. Tobramycin exposure from active calcium sulfate bone graft substitute. BMC Pharmacol Toxicol. 2014;15(1):12.
42.
ShenLDongYZhangC, et al.Chronic osteomyelitis treatment: a clinical and pharmaco-kinetic study of vancomycin impregnated calcium sulphate. J Med Imaging Heal Informatics. 2014;5(1):36–42. doi:10.1166/jmihi.2015.1362
43.
BruceASWKerryRMNormanPStockleyI. Fluconazole-impregnated beads in the management of fungal infection of prosthetic joints. J Bone Joint Surg Br. 2001;83(2):183–184. doi:10.1302/0301-620x.83b2.11444
44.
ManoliTRahmanian-SchwarzAKonheiserKGonserPSchallerHE. The role of antibiotics after surgical treatment of simple hand infections: a prospective pilot study. J Investig Surg. 2013;26(5):229–234. doi:10.3109/08941939.2012.747576
45.
AlongeTOOgunladeSOOmololuAB. The Belfast technique for the treatment of chronic osteomyelitis in a tropical teaching hospital. Int Orthop. 2003;27(2):125–128. doi:10.1007/s00264-002-0416-7
46.
PeachCANicolettiSLawrenceTMStanleyD. Two-stage revision for the treatment of the infected total elbow arthroplasty. Bone Joint J. 2013;95 B(12):1681–1686. doi:10.1302/0301-620X.95B12.31336
47.
BenaertsPJRidlerBMFVercaerenPThompsonJFCampbellWB. Gentamicin beads in vascular surgery: long-term results of implantation. Cardiovasc Surg. 1999;7(4):447–450.
48.
GaulandC. Managing lower-extremity osteomyelitis locally with surgical debridement and synthetic calcium sulfate antibiotic tablets. Adv Skin Wound Care. 2011;24(11):515–523. doi:10.1097/01.ASW.0000407647.12832.6c
49.
AmmonPStockleyI. Allograft bone in two-stage revision of the hip for infection. J Bone Joint Surg Br. 2004;86-B(7):962–965. doi:10.1302/0301-620x.86b7.14292
50.
OsmonDRBerbariEFBerendtAR, 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):1–10. doi:10.1093/cid/cis966
51.
KretlowJDBrownRHWolfswinkelEM, et al.Salvage of infected left ventricular assist device with antibiotic beads. Plast Reconstr Surg. 2014;133(1):28e–38e.
52.
OkaharaKKambayashiJShibuyaT, et al.An infection-resistant PTFE vascular graft; spiral coiling of the graft with ofloxacin-bonded PTFE thread. Eur J Vasc Endovasc Surg. 1995;9(4):408–414. doi:10.1016/S1078-5884(05)80008-5
53.
ChervuAMooreWSChvapilMHendersonT. Efficacy and duration of antistaphylococcal activity comparing three antibiotics bonded to Dacron vascular grafts with a collagen release system. J Vasc Surg. 1991;13(6):897–901. doi:10.1016/0741-5214(91)90057-2
54.
StonePAArmstrongPABandykDF, et al.Use of antibiotic-loaded polymethylmethacrylate beads for the treatment of extracavitary prosthetic vascular graft infections. J Vasc Surg. 2006;44(4):757–761. doi:10.1016/j.jvs.2006.05.056
55.
PoiMJPisimisisGBarshesNR, et al.Evaluating effectiveness of antibiotic polymethylmethacrylate beads in achieving wound sterilization and graft preservation in patients with early and late vascular graft infections. Surgery. 2013;153(5):673–682. doi:10.1016/j.surg.2012.10.011
56.
StonePAMousaAYHassSM, et al.Antibiotic-loaded polymethylmethacrylate beads for the treatment of extracavitary vascular surgical site infections. J Vasc Surg. 2012;55(6):1706–1711. doi:10.1016/j.jvs.2011.12.037
57.
GenoveseEAAvgerinosEDBarilDTMakarounMSChaerRA. Bio-absorbable antibiotic impregnated beads for the treatment of prosthetic vascular graft infections. Vascular. 2016;24(6):590–597. doi:10.1177/1708538116630859
58.
WilsonAPRGibbonsCReevesBC, et al.Information in practice. Surgical wound infection as a performance indicator: agreement of common definitions of wound infection in 4773 patients. BMJ. 2004;329(7468):720. doi:10.1136/bmj.38232.646227.DE
SahBRHusmannLMayerD, et al.Diagnostic performance of 18F-FDG-PET/CT in vascular graft infections. Eur J Vasc Endovasc Surg. 2015;49(4):455–464. doi:10.1016/j.ejvs.2014.12.024
61.
Reinders FolmerEIVon MeijenfeldtGCIVan der LaanMJ, et al.Diagnostic imaging in vascular graft infection: a systematic review and meta-analysis. Eur J Vasc Endovasc Surg. 2018;56(5):719–729. doi:10.1016/j.ejvs.2018.07.010
62.
OstermannPASeligsonDHenrySL. Local antibiotic therapy for severe open fractures. A review of 1085 consecutive cases. J Bone Joint Surg Br. 1995;77(1):93–97.
63.
KrauseFGdeVriesGMeakinCKallaTPYoungerASE. Outcome of transmetatarsal amputations in diabetics using antibiotic beads. Foot Ankle Int. 2009;30(6):486–493.
64.
SalgamiE VBowlingFLWhitehouseRWBoultonAJ. Use of tobramycin-impregnated calcium sulphate pellets in addition to oral antibiotics: an alternative treatment to minor amputation in a case of diabetic foot osteomyelitis. Diabetes Care. 2007;30(1):181–182. doi:30/1/181-a [pii]
65.
MorleyRLopezFWebbF. Calcium sulphate as a drug delivery system in a deep diabetic foot infection. Foot. 2016;27:36–40. doi:10.1016/j.foot.2015.07.002
66.
RoederBVan GilsCCMalingS. Antibiotic beads in the treatment of diabetic pedal osteomyelitis. J Foot Ankle Surg. 2000;39(2):124–130. doi:10.1016/S1067-2516(00)80037-X
67.
JogiaRMModhaDENisalKBerringtonRKongMF. Use of highly purified synthetic calcium sulfate impregnated with antibiotics for the management of diabetic foot ulcers complicated by osteomyelitis. Diabetes Care. 2015;38(5): e79–80. doi:10.2337/dc14-3100
68.
MoherDLiberatiATetzlaffJAltmanDG. The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6(6): e1000097. doi:10.1371/journal.pmed1000097
