Abstract Introduction Inflatable penile prostheses (IPP) experience surface-associated bacterial biofilms, which may contribute to clinical infections. Current attempts to reduce bacterial colonization include antibiotic coatings, altered implant surface binding properties, and mechanical irrigations. 0.05% chlorhexidine gluconate (CHG) has been proposed as a hydrophilic surface coating and mechanical irrigation for IPP surgery. One study demonstrated reduced surface bacterial colonization on an IPP hydrophilic surface dipped and irrigated with CHG 15psi compared to normal saline. However, CHG’s efficacy has not been compared to that of an antibiotic, particularly in preventing colonization by bacteria that are commonly implicated in IPP infections. Objective To characterize the utility of 0.05% chlorhexidine or vancomycin/gentamicin (VG) as both an antibiotic dip and an intraoperative irrigation in reducing bacterial colonization on hydrophilic IPP surfaces. Methods Sterile 8mm diameter IPP pieces (Coloplast, Minneapolis, MN) underwent the following treatment protocols. 1: IPP pieces were split into three groups (10 replicates each) and submerged for 3 minutes in normal saline (NS), 0.05% CHG in sterile water (Irrimax, Lawrenceville, GA), or a solution of 2mg/mL vancomycin and 160μg/mL gentamicin (VG) (Sigma-Aldrich, Burlington, MA) 2: IPP pieces were split into six groups (>14 replicates each) and submerged for 3 minutes in either NS, 0.05% CHG, or VG. Pieces were then rinsed in NS for five seconds and re-submerged in a separate well containing NS, 0.05% CHG, or VG. The pieces were rinsed in NS to remove any unbound solution and then incubated with 1*10^5 CFU/mL of methicillin-sensitive Staphylococcus aureus ATCC25923 in trypticase soy broth (TSB) for 48 hours. Samples were then rinsed with PBS and adherent bacteria were removed by shaking in 0.3% Tween-20. Suspended bacteria were serially diluted, plated onto 3M PetriFilms (Maplewood, MN), and counted. Mann-Whitney U tests were performed to compare outcomes, p<0.05 considered significant. Results Average bacterial counts with 95% CI’s for protocols 1 and 2 are plotted in Figures 1a and 1b respectively. NS controls showed an average of 1.1E7 CFU/mL adherent bacteria. Pre-dipping the implant in 0.05% CHG inhibits bacterial growth with a nearly ~2 log decrease (4.9E5 CFU/mL, p<0.01) in counts. Pre-dipping with VG had greater potency, with a ~5 log decrease (3.7E1 CFU/mL. p<0.01). However, exposure of the previously dipped IPP surface to an antiseptic irrigation solution altered antimicrobial properties (Figure 1b). NS controls showed an average of 6.0E7 CFU/mL adherent bacteria. The introduction of NS or CHG to the VG-coated implant material resulted in a near-complete loss of antimicrobial efficacy, with a 0.5 log decrease (NS) and a slight increase (CHG) in bacterial growth (NS: 5.5E7 CFU/mL, p=0.433; CHG: 6.2E7, p=.983). VG dipping followed by VG irrigation resulted in retention of antimicrobial properties, with a similar 5 log decrease. Conclusions Dipping of the implant surface with VG was more effective than 0.05% CHG. Furthermore, the choice of irrigation solution appears to alter the efficacy of antimicrobials bound to the hydrophilic IPP surface. Surgeons should be cautious using CHG or NS as an irrigation solution, and, if utilized, should take care to limit the contact time with the antibiotic-coated implant. Disclosure Yes, this is sponsored by industry/sponsor: Coloplast (material not financial support). Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast and Boston Scientific.