Ortero, Judith Alvarez

Abstract Background Chronic periprosthetic joint infection is commonly managed with two-stage exchange. Clinically, evaluation for persistent infection at the second stage of exchange may inform management. The aim of this study was to evaluate the yield of periprosthetic tissue and antimicrobial-containing cement spacer sonicate fluid cultures at the second stage of two-stage exchange surgeries. Methods Periprosthetic tissue and sonicate fluid cultures of hip and knee cement spacers removed at the second stage of two-stage exchange surgeries between January 2010 and December 2020 were studied. Two or more positive tissue cultures yielding the same organism were considered positive. For sonicate culture, ≥20 CFU/10 ml of sonicate fluid was considered positive. Persistent infection was defined by the presence of at least one of the following: intraoperative purulence, sinus tract, histopathology showing acute inflammation, or clinical signs of infection. Cement spacers were removed as part of spacer exchange if persistent infection was suspected or for insertion of a new implant if infection was not suspected. Results 172 cultures were evaluated, 69% from knees and 31% from hips. Median patient age was 64 years; 53% were men. 38/172 (22%) of cement spacers were removed as part of a spacer exchange and 134/172 (78%) for insertion of a new implant. Persistent infection was present in 49/172 (28%). 18/172 (10%) received antibiotics 2 weeks before culture, including 8/18 (44%) undergoing spacer exchange. For persistent infections, tissue and sonicate culture were positive in 11/49 and 5/49, respectively. In the 123 without persistent infection, no tissue or sonicate cultures were positive. When a new implant was placed, persistent infection was observed in 18/134 (13%), and tissue and sonicate cultures were positive in 4/18 and 1/18, respectively. When a new implant was placed (116) and no infection was found, all tissue and sonicate cultures were negative. After spacer exchange, persistent infection was present in 31/38 (81%), and tissue and sonicate cultures were positive in 8/31 and 3/31, respectively; in the 7 without infection, there were no positive cultures. Conclusion Sonication culture of cement spacers and periprosthetic tissue cultures have low sensitivities for persistent infection. Disclosures Matthew Abdel, MD, Stryker: Advisor/Consultant|Stryker: Royalties Nicholas Bedard, MD, Stryker: Advisor/Consultant Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria

Abstract Background Treatment of high risk AmpC-producing Enterobacterales bloodstream infections (BSIs) is challenging due to the posibility of development of antibiotic resistance during treatment. The aim of this study was to analyze the impact of antimicrobial stewardship activity and IDSA guidelines adequacy in patients with high risk AmpC-producing Enterobacterales BSIs. Methods Patients with Citrobacter spp, Enterobacter spp and Klebsiella aerogenes BSIs were included between June 2019-March 2024. Outcomes of death and relapse of infection at 30 days were assessed. Adequacy of definitive antimicrobial treatment according to IDSA guidelines was evaluated. The impact of antimicrobial stewardship activity in treatment adequacy and outcome was analyzed. Analysis was performed using SPSS version 25. Results 2049 BSIs were evaluated and 67 were finally included. 80% were monomicrobial. Median patient age was 74 years, 73% were male. The most frequent microorganism isolated was Enterobacter cloacae (55%). 50% were nosocomial and the most frequent origen was biliary tract (35,8%). 35% met sepsis criteria. 30% of cases presented cefotaxim resistance. Empiric and definitive antibiotic treatment was prescribed according IDSA guidelinesi n 34% and 91% of cases, respectively.. Death at 30 days was 6% and a combination outcome of death and relapse of infection at 30 days was 11,9%. Definitive antibiotic treatment adequacy according to IDSA guidelines was associated with lower mortality and relapse at 30 days (OR 0,04; IC95 0,003-0,6; P=0,02). Antimicrobial stewardship team did an intervention in 34% cases. This intervention was associated with a trend toward of lower mortality and relapse (4% vs 15%, P=0,2), a trend toward of higher IDSA guidelines adequacy (100% vs 86%, P=0,08), and a higher switch to oral treatment (78% vs 52%; P=0,03). Conclusion Adequacy of definitive antimicrobial treatment in high risk AmpC producing Enterobacterales BSIs according to IDSA guidelines was associated with a better outcome. Antimicrobial stewardship is desired for management of these patients. Disclosures All Authors: No reported disclosures

Abstract Background Biofilms formed by antibiotic-resistant bacteria in wound beds present unique challenges in terms of treating wound infections. In this work, the in vivo anti-biofilm activity of a novel electrochemical bandage (e-bandage) designed to continuously deliver low amounts of hypochlorous acid (HOCl) was evaluated against wound biofilm infections caused by a clinical isolate of Pseudomonas aeruginosa resistant to all antibiotic classes except aminoglycosides. Methods 5 mm skin wounds were created on the dorsal surface of Swiss-Webster mice and infected with 106 CFU of P. aeruginosa. Biofilms were allowed to form over 2 days, after which e-bandages with Tegaderm™ or Tegaderm only were placed on the wound beds. Specifically, mice were randomized to one of three experimental groups (n = 7-8): 1) Tegaderm only (control); 2) non-polarized e-bandage; 3) polarized e-bandage using a wearable potentiostat. After 48 hours, animals were sacrificed and 10 mm skin biopsies containing the wound and surrounding tissue were harvested for bacterial quantification. Histopathology was performed on H&E-stained sections of wound beds from each treatment group. Blood was screened with an inflammatory cytokine panel. Wound healing (% area reduction; digital measurement) and purulence (observational scoring) were assessed in pre- and post-treatment wounds. Results 48 hours of polarized e-bandage treatment resulted in a mean reduction of 1.86 log10 biofilm CFUs/g (p < 0.0001) vs non-polarized controls, and 2.18 log10 CFU/g reduction (p < 0.0001) vs Tegaderm only controls (polarized, 7.6 ± 0.66 log10 CFU/g; non-polarized, 9.45 ± 0.26 log+10 CFU/g; Tegaderm only, 9.78 ± 0.16 log10 CFU/g). Compared to Tegaderm only, purulence reduction and wound healing were significantly higher for both non-polarized (purulence - p < 0.0001; healing - p < 0.01 ) and polarized treatment (purulence - p < 0.0001; healing - p < 0.0001) groups, but were not significantly different from each other. Histopathology and blood inflammation panel testing showed no significant differences between groups. Conclusion An HOCl-producing e-bandage reduced P. aeruginosa in wound biofilms, representing a potential antibiotic-free strategy for the treatment of recalcitrant wound infections. Disclosures Audrey N. Schuetz, MD, Merck: Advisor/Consultant Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant

Abstract Background Periprosthetic joint infection (PJI) is a devastating complication following joint replacement, associated with morbidity and mortality. Here, we established a clinically representative murine model of knee arthroplasty and determined the ideal bacterial inoculum that would result in PJI without causing significant limb compromise.Figure 1.An example of an uninfected titanium prosthesis osseointegrated into the tibia of a mouse. Methods A titanium tibial prosthesis designed for the murine knee was 3D printed and surgically implanted into the proximal tibia (Figure 1) of 38 C57BL/6 mice. The prosthesis is designed to osseointegrate into the tibia and has a smooth articular surface to allow for immediate weight bearing and range of motion. At the time of surgery, the arthroplasty was inoculated with five inocula of Staphylococcus aureus Xen36, ranging from 29 to 14,000 colony forming units (CFU) (Table 1). Mice were sacrificed at 3 weeks, or earlier if necessary due to infectious sequelae, and the joint tissue, tibia, femur, and prosthesis quantitatively cultured. Results All mice inoculated with 181 to 14,000 CFU developed PJI as did 90% inoculated with 29 CFU. Bacterial loads from joint tissues and tibial prostheses are shown in Table 1. All mice inoculated with 14,000 and 760 CFU had overt findings of infection (abscesses, sinus tracts, significant limb dysfunction) requiring early euthanasia (Table 2). Mice inoculated with 640 CFU had swelling, redness, and small sores in first 3 days, and 1 death, but otherwise appeared well; only 2/9 had a visible abscess at 3-week sacrifice. 2/10 mice receiving 181 CFU had small sores that resolved in the first week; all limbs functioned well prior to sacrifice. Mice receiving 29 CFU had no external evidence of infection, however 9/10 had purulence within the joint at sacrifice. Conclusion This study demonstrates that inoculum size directly impacts clinical manifestations of infection in a murine model of S. aureus PJI. An inoculum of 181 CFU resulted in universal infection without significantly compromising the limb. The ability of this model to create PJI without overt infectious sequela will allow for evaluation of therapeutics, including those locally delivered. Disclosures Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant Nicholas Bedard, MD, Stryker: Advisor/Consultant