Rafael Carrion, MD Associate Professor of Urology University of South Florida School of Medicine

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1 Rafael Carrion, MD Associate Professor of Urology University of South Florida School of Medicine

2 Prosthetics Most catastrophic complication is infection Original estimates were calculated: Virgin 3-5% Diabetics 5-8% Revision 10% New Retardant Coatings (hydrophillic and Inhibizone) have decreased infection risk by 50% Jarow JP. Risk factors for penile prosthetic infection. J Urol 1996;156: Wilson SK, Carson CC, Cleves MA, Delk JR 2nd. Quantifying risk of penile prosthesis infection with elevated glycosylated hemoglobin. J Urol 1998;159: Wilson SK, Henry GD, Delk JR, Cleves M. Prevention of infection in revision of penile prosthesis using antibiotic coated prosthesis and Mulcahy salvage protocol. J Urol 2003;169:325, abs # Carson CC. Efficacy of antibiotic impregnation of inflatable prostheses in decreasing infection in original implants. J Urol 2004;171:

3 Prosthetics Implant infections are significantly caused by Staphylococci species (might be changing with new coated penile prosthetics) Much of the research has focused on this bacteria in relation to: Structural molecules Synthesis and genetics of biofilms Network of signal factors that provide control

4 Biofilm Despite the many possible definitions, bacterial biofilms can simply be described as a structured consortium of bacteria encased in a self-produced matrix. Bacterial Biofilm is formed around prosthetic material This is a consistent process Process involves various stages C.R. Arciola, J.W. Costerton et al. / Biomaterials 33 (2012) 5967e5982

5 Biofilm Device becomes contaminated with microorganisms during original surgery Initially they are considered planktonic Freely swim around spaces by prosthetic With multiplication, Race for the Surface Bacteria trying to reach and adhere to surface of prosthetic VS host macrophages and preoperative antimicrobials killing them Costerton JW, et al. Bacterial biofilms: A common cause of persitent infection. Science 1999;284: Costerton JW, Montanaro L, Arciola CR. Biofilm in implant infections: its production and regulation. Int J Artif Organs 2005;28(11):1062e8

6 Biofilm Formation of Actual Biofilm: Bacteria secrete adhesion molecules to attach to prosthetic material The attached bacterial colonies secrete extracellular polymers and form matrix This equals Biofilm! Structure is varied With channels that allow for transport of nutrients, water, and oxygen Jefferson KK. What defines bacteria to produce a biofilm? FEMS Microbiol Lett 2004;236: Costerton JW, Montanaro L, Arciola CR. Biofilm in implant infections: its production and regulation. Int J Artif Organs 2005;28(11):1062e8

7 Biofilm Consists of: Exopolysaccherides Proteins Teichoic acids Extracellular DNA (edna) These substances are dependant on the bacterial species, strain type, and environment

8 Biofilm Stages of Formation: Initial attachment of bacterial cells Cell aggregation and accumulation in multiple layers Biofilm maturation Detachment of cells from biofilm into a planktonic state to initiate a new cycle of biofilm formation

9 (Microbial surface components recognizing adhesive matrix molecules) C.R. Arciola, J.W. Costerton et al. / Biomaterials 33 (2012) 5967e5982

10 C.R. Arciola, J.W. Costerton et al. / Biomaterials 33 (2012) 5967e5982

11 Mechanisms Governing Expression of Biofilm The production of staphylococcal biofilm is under the control of a complex network of signal molecules acting either on the activation or on the inhibition of the expression of well defined biofilm components.

12 Scheme illustrating the complex signaling network governing biofilm expression In S. aureus based on current evidences C.R. Arciola, J.W. Costerton et al. / Biomaterials 33 (2012) 5967e5982

13 Biofilm Compromise the Host Immune Response Slime decreases phagocytic activity of neutrophils Optimizes resistance to Antimicrobial agents Bacteria in slime have reduced growth rates Allows Bacteria to resist antimicrobial agents unless extremely higher concentrations exist

14 Antimicrobial depletion (the agent does not reach the biofilm) Slow penetration (giving biofilm cells a chance to initiate stress responses) Stress response (cells change activity in response to environmental challenge) Altered microenvironment (metabolically inactive, though viable cells) "Persister" cells (spore-like cells that may survive an antimicrobial challenge)

15 Biofilm Within the slime: Bacteria can exchange genetic material Offers flexibility of different phenotypes This optimizes Bacterial Resistance to Antimicrobial agents

16 Host Response to Biofilm C.R. Arciola, J.W. Costerton et al. / Biomaterials 33 (2012) 5967e5982

17 Host Response to Biofilm C.R. Arciola, J.W. Costerton et al. / Biomaterials 33 (2012) 5967e5982

18 Host Response to Biofilm C.R. Arciola, J.W. Costerton et al. / Biomaterials 33 (2012) 5967e5982

19 Host Response to Biofilm C.R. Arciola, J.W. Costerton et al. / Biomaterials 33 (2012) 5967e5982

20 Published in: Science, 21 May 1999, VOL 284 P. Dirckx 99 MSU CBE

21 Biofilm Future Investigation Matrix is a porous network Fluids run along channels These properties allow for development of antibiofilm therapies Staphlococcal biofilm disruption enyzme: Deoxyribonuclease I (Dnase I) Degrades edna Disperson B (DspB) Lyses poly-(β-1,6)-n-acetylglucosamine (PNAG)

22 Biofilm Future Investigation In Vivo Models: DspB with antiseptics (triclosan or chlorhexadine) gave synergistic broad spectrum anti-biofilm and anti-microbial activity Maggot or larvae therapy N-acetylcysteine (NAC) Darouiche RO et al. Efficacy of combination of chlorhexidine and protamine sulphate against deviceassociated pathogens. J Antimicrob Chemother 2008;61:651e7. Darouiche RO et al. Antimicrobial and antibiofilm efficacy of triclosan and DispersinB combination. J Antimicrob Chemother 2009;64:88e93. Harris LG et al. Disruption of Staphylococcus epidermidis biofilms by medicinal maggot Lucilia sericata excretions/secretions. Int J Artif Organs 2009;32(9):555e64. Schwandt LQ et al. Prevention of biofilm formation by dairy products and N-acetylcysteine on voice prostheses in an artificial throat. Acta Otolaryngol 2004;124:726e31. Aslam S, Darouiche RO, et al. Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters. Antimicrob Agents Chemother 2007;51:1556e8.

23 Anti-Biofilm Strategy

24 Anti-Biofilm Strategy A "locking" analogue of a specific detachment signal releases biofilm cells to the planktonic state, rendering them susceptible to antibiotics.

25 Role of Biomaterial Future Goal Standard? Search for material that provides Antimicrobial activity Antibiotic loaded materials Anti-adhesion heparin Anti-biofilm quaternised chitosan derivatives N,N-hexyl,methyl-polyethylenimine (HMPEI) Support tissue integration nanomaterials

26 Penile Prosthesis and Biofilm Biofilm found on clinically uninfected implant components SK Wilson, JW Costerton. Biofilm and Penile Prosthesis Infections in the Era Of Coated Implants: A Review. J Sex Med 2012;9:44 53

27 J Urol 2004;172:153 6

28 J Urol 2004;172:153 6

29 J Urol 2004;172:153 6

30 J Urol 2004;172:153 6

31 J Urol 2004;172:153 6

32 J Urol 2008;179:186 90

33 J Urol 2008;179:186 90

34 J Urol 2008;179:186 90

35 J Urol 2008;179:186 90

36 Confocal Scanning Laser Microscopy Virulence 2:5, ; September/October 2011; 2011 Landes Bioscience

37 Modern Penile Prosthesis Infection Retardant Coatings American Medical Systems Antimicrobial impregnation Coloplast Hydrophilic coating

38 InhibiZone InhibiZone is a proprietary combination: Rifampin and Minocyline A manufacturing process that impregnates the antibiotics into the prosthetic surfaces that contact tissue The silicone surfaces of the prosthesis have a yellow-orange mottled appearance resulting from the presence of antibiotics.

39 Hydrophilic = Water Loving Such compounds (or coatings) have an affinity to water and are usually charged or have polar side groups to their structure that will attract water

40 An approach to achieve Anti-Adherence anti-microbial surfaces Increased lubriciousness of the surface* Reduce the likelihood that potentially pathogenic organisms will cause an infection by reducing adherence of the organism Potential for reduction of biofilm formation Release of Antimicrobial Agents Potential localized elution in implant space *Wolter, Hellstrom et al. The hydrophilic coated implant... J Sex Med :221

41 J. William Costerton, PhD Univ. of British Columbia BSc & MS Bacteriology and Immunology University of Western Ontario PhD Bacteriology University of Calgary Post Doc studies Microbiology Montana State Univ. Director of the Center for Biofilm Engineering University of Southern California School of Dentistry Established first Biofilm Center at a University

42 Thank You