Abstract
Implant-related infections are among the main reasons for joint arthroplasty and osteosynthesis failure. Despite host’s immune system and antibiotic prophylaxis, implant infection may follow bacterial adhesion to biomaterials and biofilm formation, a main reason for bacterial persistence.
Over the past 20 years, a wide range of different antibiofilm agents have been investigated both in vitro and in vivo. The results that emerged are promising, though their implementation in orthopedics is still at an early stage. Here we review the main results and propose an original classification of antibiofilm agents, sorted according to their action mechanism. Molecules interfering with biofilm formation (biofilm prevention agents) include anti-adhesion compounds, quorum-sensing inhibitors, nonsteroidal anti-inflammatory drugs, antimicrobial peptides, and active bioglass. N-Acetylcysteine and specific enzymes are able to disrupt already established biofilms (biofilm-disrupting agents). An alternative approach relies on the identification of antimicrobials able to bypass the biofilm barrier (biofilm-bypassing agents) and on the development of antibiofilm vaccine. Local application of antibacterial and antibiofilm agents, like implant coating, is a feasible and promising approach, while systemic antibiofilm treatment is still restricted to animal models. Further research in this promising field appears necessary.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Abdelghany SM, Quinn DJ, Ingram RJ, Gilmore BF, Donnelly RF, Taggart CC, Scott CJ (2012) Gentamicin-loaded nanoparticles show improved antimicrobial effects towards Pseudomonas aeruginosa infection. Int J Nanomedicine 7:4053–4063
Alem MA, Douglas J (2004) Effects of aspirin and other nonsteroidal anti-inflammatory drugs on biofilms and planktonic cells of Candida albicans. Antimicrob Agents Chemother 1:41–47
Anguita-Alonso P, Giacometti A, Cirioni O, Ghiselli R, Orlando F, Saba V (1998) RNAIII-inhibiting-peptide loaded polymethylmethacrylate prevents in vivo Staphylococcus aureus biofilm formation. Antimicrob Agents Chemother 51:2594–2596
Arciola CR (2009) New concepts and new weapons in implant infections. Int J Artif Organs 32:533–536
Arciola CR, Montanaro L, Costerton JW (2011) New trends in diagnosis and control strategies for implant infections. Int J Artif Organs 34:727–736
Artini M, Romanò CL, Manzoli L, Scoarughi GL, Papa R, Meani E (2011a) Staphylococcal IgM enzyme-linked immunosorbent assay for diagnosis of periprosthetic joint infections. J Clin Microbiol 49(1):423–425
Artini M, Scoarughi GL, Papa R, Cellini A, Carpentieri A, Pucci P (2011b) A new anti-infective strategy to reduce adhesion-mediated virulence in Staphylococcus aureus affecting surface proteins. Int J Immunopathol Pharmacol 24:661–672
Aslam S, Darouiche RO (2011) Role of antibiofilm-antimicrobial agents in controlling device-related infections. Int J Artif Organs 34:752–758
Aslam S, Trautner BW, Ramanathan V, Darouiche RO (2007) Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters. Antimicrob Agents Chemother 51:1556–1558
Balaban N, Goldkorn T, Nhan RT, Dang LB, Scott S, Ridgley RM (1998) Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus. Science 280:438–440
Bozic KJ, Kurtz SM, Lau E, Ong K, Chiu V, Vail TP (2010) The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res 468:45–51
Brackman G, Cos P, Maes L, Nelis HJ, Coenye T (2011) Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrob Agents Chemother 55:2655–2661
Brady RA, Leid JG, Camper AK, Costerton JW, Shirtliff ME (2006) Identification of Staphylococcus aureus proteins recognized by the antibody-mediated immune response to a biofilm infection. Infect Immun 74:3415–3426
Brady RA, O’May GA, Leid JG, Prior ML, Costerton JW, Shirtliff ME (2011) Resolution of Staphylococcus aureus biofilm infection using vaccination and antibiotic treatment. Infect Immun 79:1797–1803
Brown MR, Allison DG, Gilbert P (1988) Resistance of bacterial biofilms to antibiotics: a growth-rate related effect? J Antimicrob Chemother 22:777–780
Burygin GL, Khlebtsov BN, Shantrokha AN, Dykman LA, Bogatyrev VA, Khlebtsov NG (2009) On the enhanced antibacterial activity of antibiotics mixed with gold nanoparticles. Nanoscale Res Lett 4(8):794–801
Cazander G, van de Veerdonk MC, Vandenbroucke-Grauls CM, Schreurs MW, Jukema GN (2010) Maggot excretions inhibit biofilm formation on biomaterials. Clin Orthop Relat Res 468(10):2789–2796
Chen WH, Jiang LS, Dai LY (2011) Influence of bacteria on spinal implant-centered infection: an in vitro and in vivo experimental comparison between Staphylococcus aureus and mycobacterium tuberculosis. Spine 36:103–108
Christensen LD, van Gennip M, Jakobsen TH, Alhede M, Hougen HP, Høiby N, Bjarnsholt T, Givskov M (2012) Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model. J Antimicrob Chemother 67(5):1198–1206
Cirioni O, Giacometti A, Ghiselli R, Kamysz W, Orlando F, Mocchegiani F et al (2006) Citropin 1.1-treated central venous catheters improve the efficacy of hydrophobic antibiotics in the treatment of experimental staphylococcal catheter-related infection. Peptides 27:1210–1216
Cirioni O, Ghiselli R, Minardi D, Orlando F, Mocchegiani F, Silvestri C (2007) RNAIII-inhibiting peptide affects biofilm formation in a rat model of staphylococcal ureteral stent infection. Antimicrob Agents Chemother 51:4518–4520
Cirioni O, Mocchegiani F, Ghiselli R, Silvestri C, Gabrielli E, Marchionni E (2010) Daptomycin and rifampin alone and in combination prevent vascular graft biofilm formation and emergence of antibiotic resistance in a subcutaneous rat pouch model of Staphylococcal infection. Eur J Vasc Endovasc Surg 40:817–822
Coenye T, Nelis HJ (2010) In vitro and in vivo model systems to study microbial biofilm formation. J Microbiol Methods 83:89–105
Cole N, Hume EB, Vijay AK, Sankaridurg P, Kumar N, Willcox MD (2010) In vivo performance of melimine as an antimicrobial coating for contact lenses in models of CLARE and CLPU. Invest Ophthalmol Vis Sci 51:390–395
Costerton JW (2005) Biofilm theory can guide the treatment of device-related orthopaedic infections. Clin Orthop Relat Res 437:7–11
Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322
Costerton JW, Montanaro L, Arciola CR (2005) Biofilm in implant infections: its production and regulation. Int J Artif Organs 28:1062–1068
Darouiche RO, Dhir A, Miller AJ, Landon GC, Raad II, Musher DM (1994) Vancomycin penetration into biofilm covering infected prostheses and effect on bacteria. J Infect Dis 170:720–723
Darouiche RO, Mansouri MD, Gawande PV, Madhyastha S (2008) Efficacy of combination of chlorhexidine and protamine sulphate against device-associated pathogens. J Antimicrob Chemother 61:651–657
Darouiche RO, Mansouri MD, Gawande PV, Madhyastha S (2009) Antimicrobial and antibiofilm efficacy of triclosan and DispersinB combination. J Antimicrob Chemother 64:88–93
del Prado G, Ruiz V, Naves P, Rodrı’guez-Cerrato V, Soriano F, del Carmen Ponte M (2010) Biofilm formation by Streptococcus pneumoniae strains and effects of human serum albumin, ibuprofen, N-acetyl-L-cysteine, amoxicillin, erythromycin, and levofloxacin. Diagn Microbiol Infect Dis 67:311–318
Di Poto A, Sbarra MS, Provenza G, Visai L, Speziale P (2009) The effect of photodynamic treatment combined with antibiotic action or host defence mechanisms on Staphylococcus aureus biofilms. Biomaterials 30:3158–3166
Drago L, de Vecchi E, Nicola L, Valli M, Gismondo MR (2002) Effects of subinhibitory concentrations of ibuprofen isobuthanolammonium on virulence factors of uropathogenic Escherichia coli. J Chemother 14:314–315
Drago L, Romanò CL, Mattina R, Signori V, de Vecchi E (2012) Does dithiothreitol improve bacterial detection from infected prosthesis ? A pilot study. Clin Orthop Relat Res. doi:10.1007/s11999-012-2415-3
Drago L, Mattina R, Signori V, De Vecchi E, Romanò CL (2013) Activity of N-acetyl-L-cysteine against biofilm of Staphylococcus aureus and Pseudomonas aeruginosa on orthopaedic prosthetic materials. Int J Artif Organs. doi:10.5301/ijao.5000135
Drago L, Boot W, Dimas K, Malizos K, Hänsch GM, Stuick J, Gawlitta D, Romanò CL (2014) Does implant coating with antibacterial-loaded hydrogel reduce bacterial colonization and biofilm formation in vitro? Clin Orthop Relat Res. doi: 10.1007/s11999-014-3558-1
Drenkard E, Ausubel FM (2002) Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416:740–743
Eckert R, Qi F, Yarbrough DK, He J, Anderson MH, Shi W (2006) Adding selectivity to antimicrobial peptides: rational design of a multidomain peptide against Pseudomonas spp. Antimicrob Agents Chemother 50:1480–1488
El-Feky MA, El-Rehewy MS, Hassan MA, Abolella HA, Abd El-Baky RM, Gad GF (2009) Effect of ciprofloxacin and N-acetylcysteine on bacterial adherence and biofilm formation on ureteral stent surfaces. Pol J Microbiol 58:261–267
Farber BF, Wolff AG (1992) The use of nonsteroidal antiinflammatory drugs to prevent adherence of Staphylococcus epidermidis to medical polymers. J Infect Dis 166:861–865
Fernebro J (2011) Fighting bacterial infections — future treatment options. Drug Resist Updat 14:125–139
Gattringer KB, Suchomel M, Eder M, Lassnigg AM, Graninger W, Presterl E (2010) Time-dependent effects of rifampicin on staphylococcal biofilms. Int J Artif Organs 33:621–626
Geske GD, Wezeman RJ, Siegel AP, Blackwell HE (2005) Small molecule inhibitors of bacterial quorum sensing and biofilm formation. J Am Chem Soc 127:12762–12763
Giacometti A, Cirioni O, Gov Y, Ghiselli R, Del Prete MS, Mocchegiani F (2003) RNAIII inhibiting peptide inhibits in vivo biofilm formation by drug-resistant Staphylococcus aureus. Antimicrob Agents Chemother 47:1979–1983
Gianfaldoni C, Maccari S, Pancotto L, Rossi G, Hilleringmann M, Pansegrau W (2009) Sortase A confers protection against Streptococcus pneumoniae in mice. Infect Immun 77:2957–2961
Giavaresi G, Meani E, Sartori M, Ferrari A, Bellini D, Sacchetta AC, Meraner J, Sambri A, Vocale C, Sambri V, Fini M, Romanò CL (2013) Efficacy of antibacterial-loaded coating in an in vivo model of acutely highly contaminated implant. Int Orthop. doi:10.1007/s00264-013-2237-2
Hansen LK, Berg K, Johnson D, Sanders M, Citron M (2010) Efficacy of local rifampin/minocycline delivery (AIGIS(RX)R) to eliminate biofilm formation on implanted pacing devices in a rabbit model. Int J Artif Organs 33:627–635
Harris LG, Bexfield A, Nigam Y, Rohde H, Ratcliffe NA, Mack D (2009) Disruption of Staphylococcus epidermidis biofilms by medicinal maggot Lucilia sericata excretions/secretions. Int J Artif Organs 32:555–564
He J, Anderson MH, Shi W, Eckert R (2009) Design and activity of a ‘dual-targeted’ antimicrobial peptide. Int J Antimicrob Agents 33:532–537
Hentzer M, Wu H, Andersen JB, Riedel L, Rasmussen TB, Bagge N (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22:3803–3815
Héquet A, Humblot V, Berjeaud JM, Pradier CM (2011) Optimized grafting of antimicrobial peptides on stainless steel surface and biofilm resistance tests. Colloids Surf B Biointerfaces 84:301–309
Hickok NJ, Shapiro IM (2012) Immobilized antibiotics to prevent orthopaedic implant infections. Adv Drug Deliv Rev 64(12):1165–1176
Hill KE, Malic S, McKee R, Rennison T, Harding KG, Williams DW (2010) An in vitro model of chronic wound biofilms to test wound dressings and assess antimicrobial susceptibilities. J Antimicrob Chemother 65:1195–1206
Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O (2010) Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 35:322–332
Hume EBH, Baveja J, Muir B, Schubert TL, Kumar N, Kjelleberg S et al (2004) The control of Staphylococcus epidermidis biofilm formation and in vivo infection rates by covalently bound furanones. Biomaterials 25:5023–5030
Jonsson IM, Mazmanian SK, Schneewind O, Bremell T, Tarkowski A (2003) The role of Staphylococcus aureus sortase A and sortase B in murine arthritis. Microbes Infect 5:775–780
Jori G (2006) Photodynamic therapy of microbial infections: state of the art and perspectives. J Environ Pathol Toxicol Oncol 25:505–519
Kaplan JB (2009) Therapeutic potential of biofilm-dispersing enzymes. Int J Artif Organs 32:545–554
Kaplan JB, Lovetri K, Cardona ST, Madhyastha S, Sadovskaya I, Jabbouri S (2012) Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci. J Antibiot 65(2):73–77
Kaufmann GF, Sartorio R, Lee SH, Mee JM, Altobell LJ 3rd, Kujawa DP (2006) Antibody interference with N-acyl homoserine lactone-mediated bacterial quorum sensing. J Am Chem Soc 128:2802–2803
Kaufmann GF, Park J, Janda KD (2008) Bacterial quorum sensing: a new target for anti-infective immunotherapy. Expert Opin Biol Ther 8:719–724
Kiedrowski MR, Horswill AR (2011) New approaches for treating staphylococcal biofilm infections. Ann N Y Acad Sci 1241:104–121
Kim L (2007) Persistent cells, dormancy and infectious disease. Nat Rev Microbiol 5:48–56
Kim SW, Chang IM, Oh KB (2002) Inhibition of the bacterial surface protein anchoring transpeptidase sortase by medicinal plants. Biosci Biotechnol Biochem 66:2751–2754
Kiran MD, Giacometti A, Cirioni O, Balaban N (2008) Suppression of biofilm related, device-associated infections by staphylococcal quorum sensing inhibitors. Int J Artif Organs 31:761–770
Kurtz S, Ong K, Lau E, Mowat F, Halpern M (2007) Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 89:780–785
Lazar V (2011) Quorum sensing in biofilms — how to destroy the bacterial citadels or their cohesion/power? Anaerobe 17:280–285
Lewis K (2001) Riddle of biofilm resistance. Antimicrob Agents Chemother 45:999–1007
Li YH, Huang S, Du M, Bian Z, Chen Z, Fan MW (2010) Immunogenic characterization and protection against Streptococcus mutans infection induced by intranasal DNA prime-protein boost immunization. Vaccine 28:5370–5376
Lovetri K, Madhyastha S (2010) Antimicrobial and antibiofilm activity of quorum sensing peptides and Peptide analogues against oral biofilm bacteria. Methods Mol Biol 618:383–392
Maisch T (2007) Anti-microbial photodynamic therapy: useful in the future? Lasers Med Sci 22:83–91
Manefield M, de Nys R, Kumar N, Read R, Givskov M, Steinberg P (1999) Evidence that halogenated furanones from Delisea pulchra inhibit acylated homoserine lactone (AHL)- mediated gene expression by displacing the AHL signal from its receptor protein. Microbiology 145:283–291
Mansouri MD, Darouiche RO (2007) In vitro antimicrobial activity of N-acetylcysteine against bacteria colonising central venous catheters. Int J Antimicrob Agents 29:474–476
Marchese A, Bozzolasco M, Gualco L, Debbia EA, Schito GC, Schito AM (2003) Effect of fosfomycin alone and in combination with N-acetylcysteine on E. coli biofilms. Int J Antimicrob Agent 22:S95–S100
Maresso AW, Schneewind O (2008) Sortase as a target of antiinfective therapy. Pharmacol Rev 60:128–141
Marraffini LA, Dedent AC, Schneewind O (2006) Sortases and the art of anchoring proteins to the envelopes of gram-positive bacteria. Microbiol Mol Biol Rev 70:192–221
Mazmanian SK, Liu G, Ton-That H, Schneewind O (1999) Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science 285:760–763
McLean RJC, Lam JS, Graham LL (2012) Training the biofilm generation – a tribute to JW Costerton. J Bacteriol. doi:10.1128/JB.01252-12
Mecikoglu M, Saygi B, Yildirim Y, Karadag-Saygi E, Ramadan SS, Esemenli T (2006) The effect of proteolytic enzyme serratiopeptidase in the treatment of experimental implant-related infection. J Bone Joint Surg Am 88:1208–1214
Montanaro L, Speziale P, Campoccia D, Ravaioli S, Cangini I, Pietrocola G (2011) Scenery of Staphylococcus implant infections in orthopedics. Future Microbiol 6:1329–1349
Musk DJ Jr, Hergenrother PJ (2006) Chemical countermeasures for the control of bacterial biofilms: effective compounds and promising targets. Curr Med Chem 13:2163–2177
Naves P, del Prado G, Huelves L, Rodrı’guez-Cerrato V, Ruiz V, Ponte MC (2010) Effects of human serum albumin, ibuprofen and N-acetyl-L-cysteine against biofilm formation by pathogenic Escherichia coli strains. J Hosp Infect 76:165–170
Njoroge J, Sperandio V (2009) Jamming bacterial communication: new approaches for the treatment of infectious diseases. EMBO Mol Med 1:201–210
Nobbs AH, Lamount RJ, Jenkinson H (2009) Streptococcus adherence and colonization. Microbiol Mol Biol Rev 73:407–505
Olofsson AC, Hermansson M, Elwing H (2003) N-acetyl-L-cysteine affects growth, extracellular polysaccharide production, and bacterial biofilm formation on solid surfaces. Appl Environ Microbiol 69:4814–4822
Palmer M, Costerton W, Sewecke J, Altman D (2011) Molecular techniques to detect biofilm bacteria in long bone nonunion: a case report. Clin Orthop Relat Res 469:3037–3042
Pan JC, Ren DC (2009) Quorum sensing inhibitors: a patent review. Expert Opin Ther Pat 19:1581–1601
Park J (2007) Infection control by antibody disruption of bacterial quorum sensing signaling. Chem Biol 14(10):1119–1127
Park SC, Park Y, Hahm KS (2011) The role of antimicrobial peptides in preventing multidrug-resistant bacterial infections and biofilm formation. Int J Mol Sci 12:5971–5992
Perez-Giraldo C, Rodriguez-Benito A, Moran FJ, Hurtado C, Blanco MT, Gomez-Garcìa AC (1997) Influence of N-acetylcysteine on the formation of biofilm by Staphylococcus epidermidis. J Antimicrob Chemother 39:643–646
Poggio C, Arciola CR, Dagna A, Floridi F, Chiesa M, Saino E (2011) Photoactivated disinfection (PAD) in endodontics: an in vitro microbiological evaluation. Int J Artif Organs 34:889–897
Poultsides LA, Liaropoulos LL, Malizos KN (2010) The socioeconomic impact of musculoskeletal infections. J Bone Joint Surg Am 92:e13
Raad I, Hanna H, Jiang Y, Dvorak T, Reitzel R, Chaiban G (2007a) Comparative activities of daptomycin, linezolid, and tigecycline against catheter related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm. Antimicrob Agents Chemother 51:1656–1660
Raad I, Hanna H, Dvorak T, Chaiban G, Hachem R (2007b) Optimal antimicrobial catheter lock solution, using different combinations of minocycline, EDTA, and 25-percent ethanol, rapidly eradicates organisms embedded in biofilm. Antimicrob Agents Chemother 51:78–83
Romanò CL, Romanò D, Bonora C, Degrate A, Mineo G (2009) ‘Combined Diagnostic Tool’ for joint prosthesis infection. Infez Med 17:141–150
Romanò CL, Toscano M, Romanò D, Drago L (2013) Antibiofilm agents and implant-related infections in orthopaedics: where are we ? J Chemother 25(2):67–80
Romero D, Kolter R (2011) Will biofilm disassembly agents make it to market? Trends Microbiol 19:304–306
Saino E, Sbarra MS, Arciola CR, Scalone M, Bloise N, Nikolov P (2010) Photodynamic action of Tri-meso (N-methyl-pyridyl), meso (N-tetradecyl-pyridyl) porphine on Staphylococcus epidermidis biofilms grown on Ti6Al4V alloy. Int J Artif Organs 33:636–645
Schwandt LQ, van Weissenbruch R, Stokroos I, van der Mei HC, Busscher HJ, Albers FW (2004) Prevention of biofilm formation by dairy products and N-acetylcysteine on voice prostheses in an artificial throat. Acta Otolaryngol 124:726–731
Selan L, Berlutti F, Passariello C, Comodi-Ballanti MR, Thaller MC (1993) Proteolytic enzymes: a new treatment strategy for prosthetic infections? Antimicrob Agents Chemother 37:2618–2621
Sharma M, Visai L, Bragheri F, Cristiani I, Gupta PK, Speziale P (2008) Toluidine blue-mediated photodynamic effects on staphylococcal biofilms. Antimicrob Agents Chemother 52:299–305
Sheffner AL (1963) The reduction in vitro in viscosity of mucoprotein solutions by a new mucolytic agent, N acetyl-L-cysteine. Ann N Y Acad Sci 106:298–310
Shih PC, Huang CT (2002) Effects of quorum-sensing deficiency on Pseudomonas aeruginosa biofilm formation and antibiotic resistance. J Antimicrob Chemother 49:309–314
Shinefield H, Black S, Fattom A, Horwith G, Rasgon S, Ordonez J (2002) Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. N Engl J Med 346:491–496
Stewart PS, McFeters GA, Huang CT (2000) Biofilm control by antimicrobial agents. In: Bryers JD (ed) Biofilm: process analysis and applications. Wiley-Liss, New York, pp 373–405
Stoodley P, Conti SF, DeMeo PJ, Nistico L, Melton-Kreft R, Johnson S (2011) Characterization of a mixed MRSA/MRSE biofilm in an explanted total ankle arthroplasty. FEMS Immunol Med Microbiol 62:66–74
Taylor E, Webster TJ (2011) Reducing infections through nanotechnology and nanoparticles. Int J Nanomedicine 6:1463–1473
Tojo M, Yamashita N, Goldmann DA, Pier GB (1988) Isolation and characterization of a capsular polysaccharide adhesin from Staphylococcus epidermidis. J Infect Dis 157:713–722
Tomasz A (1965) Control of the competent state in Pneumococcus by a hormone-like cell product: an example for a new type of regulatory mechanisms in bacteria. Nature 208:155–159
Vilela SF, Junqueira JC, Barbosa JO, Majewski M, Munin E, Jorge AO (2011) Photodynamic inactivation of Staphylococcus aureus and Escherichia coli biofilms by malachite green and phenothiazine dyes: an in vitro study. Arch Oral Biol 57:704–710
Vukomanovic M, Skapin SD, Poljansek I, Zagar E, Kralj B, Ignjatovic N, Uskokovic D (2011) Poly(D, L-lactide-co-glycolide)/hydroxyapatite core-shell nanosphere. Part 2: simultaneous release of a drug and a prodrug (clindamycin and clindamycin phosphate). Colloids Surf B Biointerfaces 82(2):414–421
Watson DL (1987) Serological response of sheep to live and killed Staphylococcus aureus vaccines. Vaccine 5:275–278
Weiss WJ, Lenoy E, Murphy T, Tardio L, Burgio O, Projan SJ (2004) Effect of srtA and srtB gene expression on the virulence of Staphylococcus aureus in animal models of infection. J Antimicrob Chemother 53:480–486
Willcox MD, Hume EB, Aliwarga Y, Kumar N, Cole N (2008) A novel cationic-peptide coating for the prevention of microbial colonization on contact lenses. J Appl Microbiol 105:1817–1825
Wu H, Song Z, Hentzer M, Andresen JB, Molin S, Givskov M (2004) Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J Antimicrob Chemother 53:1054–1061
Zameer F, Gopal S (2010) Evaluation of antibiotic susceptibility in mixed culture biofilms. Int J Biotech Biochem 6:93–99
Zhang YQ, Ren SX, Li HL, Wang YX, Fu G, Yang J (2003) Genome-based analysis of virulence genes in a non-biofilm-forming Staphylococcus epidermidis strain (ATCC 12228). Mol Microbiol 49:1577–1593
Zhao T, Liu YR (2010) N-acetylcysteine inhibit biofilms produced by Pseudomonas aeruginosa. BMC Microbiol 10:140–148
Zygmunt WA, Martin TA (1968) Cysteine analogs as potential amino acid antagonists in bacteria. J Med Chem 11:623–625
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Romanò, C.L., Logoluso, N., Drago, L. (2015). Antibiofilm Strategies in Orthopedics: Where Are We?. In: Baldini, A., Caldora, P. (eds) Perioperative Medical Management for Total Joint Arthroplasty. Springer, Cham. https://doi.org/10.1007/978-3-319-07203-6_22
Download citation
DOI: https://doi.org/10.1007/978-3-319-07203-6_22
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-07202-9
Online ISBN: 978-3-319-07203-6
eBook Packages: MedicineMedicine (R0)