Aim. Polypropylene (PPE) synthetic mesh is increasingly used in knee arthroplasty surgery to salvage a disrupted extensor mechanism. Despite its clinical success, it is associated with a high rate of periprosthetic joint infection (PJI), which is hypothesized to be caused by bacterial biofilm. The purpose of the current study is to describe the progression of PPE-based biofilm formation over time and to determine if intraoperative antiseptic solutions could be used to effectively remove biofilm when treating PJI. Method. Commercially available knotted monofilament PPE mesh. 1. was cut into 10mm circular shape, immersed in tryptic soy broth (TSB) with methicillin-sensitive staphylococcus aureus and cultured individually in 48-well plates for 10 days to elucidate the biofilm grown on mesh over time. At every 24 hours, a triplicate of samples was retrieved and biofilm on the mesh was dislodged by sonicating at 52 kHz for 15 minutes and quantified by counting colony-forming units (CFUs) after overnight growth. The biofilm growth was also verified using scanning electron microscopy. The effect of saline and antiseptic solutions was verified by exposing 1) 0.05% chlorohexidine gluconate. 2. , 2) acetic acid-based mixture. 3. , 3) diluted povidone-iodine (0.35%), 4) undiluted povidone-iodine (10%). 4. , and 5) 1:1 combination of 10% povidone-iodine & 3% hydrogen peroxide on immature and mature biofilms for 3 minutes, created by culturing with bacteria for 24 hours and 72 hours respectively. All experiments were performed in quintuples and repeated. Antiseptic treatments that produced a three-log reduction in CFU counts compared to controls were considered clinically significant. Results. PPE-mesh produced reliable CFU counts at 24 hours and reached peak growth at 72 hours. For immature biofilm, all formulations of povidone-iodine produced significant reductions in CFU counts compared to controls. Although not meeting the established threshold, saline irrigation removed 86.5% of CFUs, while formulation based on chlorohexidine and acetic acid removed 99.2% and 99.7% respectively. For mature biofilm, formulations based on povidone-iodine and acetic acid produced significant reductions in CFU counts. Conclusions. Our findings suggest biofilm may form on mesh as early as 24 hours after bacterial exposure. Povidone-iodine formulations were consistently the most effective in removing biofilm on mesh surfaces. We recommend that surgeons consider using an antiseptic solution, preferably povidone-iodine-based, in addition to regular saline lavage when attempting to salvage a PPE mesh in the setting of PJI. 1. Marlex mesh (CR Bard, Davol Inc, Warwick, RI), . 2. Irrisept (Irrimax Corp, Gainesville, FL), . 3. Bactisure (Zimmer-Biomet, Warsaw, IN), . 4. Aplicare (Inc, Meriden, CT)

Summary. A meta-analysis was performed to compare rate of SSI after application of chlorhexidine vs. iodine in total joint arthroplasty. Chlorhexidine had significantly lower odds of SSI. Introduction. Surgical site infections (SSI) are a significant source of morbidity and mortality. The optimal preoperative skin preparation in lower extremity total joint arthroplasty (TJA) remains debatable between chlorhexidine and iodine-containing solutions. This meta-analysis sought compare SSI rates between chlorhexidine cloth application the night before surgery plus povidone-iodine-alcohol (povidone-iodine) solution at surgery or only povidone-iodine at surgery. Methods. A structured literature search was performed using Web of Science, PubMed, and EMBASE databases for randomized clinical trials (RCTs) and comparative studies that evaluated preoperative chlorhexidine-gluconate versus iodine-alcohol exclusively in TJA patients. Databases were searched from database inception to January 2, 2018, and studies were included if they had specific aims and 1) compared preoperative chlorhexidine-gluconate cloths to povidone-iodine at surgery, or 2) if they compared preoperative chlorhexidine-gluconate cloths and povidone-iodine at surgery, to solely povidone-iodine at surgery. The main outcome was deep or superficial SSI at or before 1 year postoperatively. If multiple studies reported the same patient cohort, the more recent study was used. To compare the chlorhexidine versus povidone-iodine groups, pooled odds ratios (OR) and 95% confidence intervals (95% CI) were used to calculate odds of SSI. Results. Four studies involving 2,997 TJA patients were included in this meta-analysis. Three were retrospective cohort studies, and one was a RCT. One retrospective cohort study assessed chlorhexidine to povidone-iodine using a historical control. One RCT compared chlorhexidine to povidone-iodine. The remaining two studies compared chlorhexidine in addition to povidone-iodine, to only povidone-iodine. Bias analysis showed low-to-moderate quality cohort studies and one moderate-quality RCT. Chlorhexidine had significantly lower odds of SSI compared to povidone iodine (OR=0.28; 95%CI: 0.15–0.51; p<0.0001). Conclusion. Preoperative chlorhexidine-gluconate was superior at reducing SSI risk in patients who underwent lower extremity TJA, compared to povidone-iodine. This can potentially lead to decreased morbidity and lower surgical revision rates for infections. For any figures or tables, please contact authors directly

Aim. The efficacy of various irrigation solutions in removing microbial contamination of a surgical wound and reducing the rate of subsequent surgical site infection (SSI), has been demonstrated extensively. However, it is not known if irrigation solutions have any activity against established biofilm. This issue is pertinent as successful management of patients with periprosthetic joint infection (PJI) includes the ability to remove biofilm established on the surface of implants and necrotic tissues. The purpose of this study was to evaluate the efficacy of various irrigation solutions in eradicating established biofilm, as opposed to planktonic bacteria, in a validated in vitro model. Method. Established biofilms of Staphylococcus aureus and Escherichia coli were exposed to different irrigation solutions that included Polymyxin 500,000U/L plus bacitracin 50,000U/L, Vancomycin 1g/L, Gentamicin 80mg/L, Normal saline 0.9%, off-the-shelf Betadine 0.3%, Chlorhexidine 0.05%, Benzalkonium 1.3g/L, Sodium hypochlorite 0.125%, and Povidone-iodine 0.5%. Each experiment was conducted in a 96-well microtiter plate with a peg lid and standardized per the MBEC assay manufacturer's protocol. Following 2 minutes of solution exposure to the irrigation solution, residual biofilms were recovered by sonication. Outcome measures for antibiofilm efficacy were residual colony forming units (CFU) and optical density (690nm). Experiments were conducted in 24 replicates and the observations recorded by two blinded observers. Statistical analysis involved t-tests with Bonferonni adjustment. Results. Povidone-iodine 0.5%, Betadine 0.3%, Benzalkonium 1.3g/L, and Sodium hypochlorite 0.125% were significantly more efficacious against S.aureus biofilm versus all other solutions (p<0.001). Against E.coli biofilm, Povidone-iodine-0.5%, Benzalkonium-1.3g/L and Sodium hypochlorite-0.125% were also most effective compared to other irrigation solutions (p<0.001). Polymyxin-bacitracin, Gentamicin, Vancomycin, and Saline solutions had minimal activity against both E.coli and S.aureus biofilms (p<0.001). Similar trends were observed using both experimental endpoints (CFU and Turbidity) and both investigators (interrater reliability; r=0.99). Conclusion. This in vitro study observed that topical antibiotic solutions do not have any activity against established biofilms. Irrigations solutions containing adequate amount of povidone-iodine, betadine, sodium hypochlorite, and benzalkonium appear to have activity against established biofilm by gram positive and gram negative organisms. The use of these irrigation solutions may need to be considered in patients with established PJI

Introduction. The use of irrigation solution during surgical procedures is a common and effective practice in reduction of bioburden and the risk of subsequent infection. The optimal irrigation solution to accomplish this feat remains unknown. Many surgeons commonly add topical antibiotics to irrigation solutions assuming this has topical effect and eliminates bacteria. The latter reasoning has never been proven. In fact a few prior studies suggest addition of antibiotics to irrigation solution confers no added benefit. Furthermore, this practice adds to cost, has the potential for anaphylactic reactions, and may also contribute to the emergence of antimicrobial resistance. We therefore sought to compare the antimicrobial efficacy and cytotoxicity of irrigation solution containing polymyxin-bacitracin versus other commonly used irrigation solutions. Methods. Using two in vitro breakpoint assays of Staphylococcus aureus (ATCC#25923) and Escherichia coli (ATCC#25922), we examined the efficacy of a panel of irrigation solutions containing topical antibiotics (500,000U/L Polymyxin-Bacitracin 50,000U/L; Vancomycin 1g/L; Gentamicin 80mg/L), as well as commonly used irrigation solutions (Normal saline 0.9%; Povidone-iodine 0.3%; Chlorhexidine 0.05%; Castile soap 0.45%; and Sodium hypochlorite 0.125%) following 1 minute and 3 minutes of exposure. Surviving bacteria were counted in triplicate experiments. Failure to eradicate all bacteria was considered to be “not effective” for that respective solution and exposure time. Cytotoxicity analysis in human fibroblast, osteoblast, and chrondrocyte cells exposed to each of the respective irrigation solutions was performed by visualization of cell structure, lactate dehydrogenase (LDH) activity and evaluation of vital cells. Toxicity was quantified by determination of LDH release (ELISA % absorbance; with higher percentage considered a surrogate for cytotoxicity). Descriptive statistics were used to present means and standard deviation of triplicate experimental runs. Results. Polymyxin-Bacitracin, Saline and Castile soap irrigation at both exposure times were not effective at eradicating S aureus or E coli (Figure 1). In contrast, Povidone-iodine, Chlorhexidine, and Sodium hypochlorite irrigation were effective at eradicating both S aureus and E coli. Vancomycin irrigation was effective at S aureus eradication but not against E coli, whereas Gentamicin irrigation showed partial efficacy against E coli eradication but none against S aureus. The greatest cytotoxicity was seen with Chlorhexidine (49.4% ± 1.9). This was followed by Castile soap (33.2% ±3.9), Vancomycin (9.01% ±5.1), Polymyxin-Bacitracin (8.45% ±1.5), and Gentamicin irrigation (4.72% ±2.3) (Figure 2 and Figure 3 microscopy images). Povidone-iodine and Sodium hypochlorite showed least cytotoxicity (0.05% ±0.08 and 0.11%±0.19, respectively). Similar trends were seen at both exposure times and across fibroblasts, osteoblasts and chondrocytes. Discussion. This in vitro study suggests that addition of polymyxin-bacitracin to saline irrigation solution is a futile exercise. Taken within the context of its associated expense, risk of hypersensitivity and impact upon antimicrobial resistance, our findings bring its widespread clinical usage into question. Povidone-iodine may be a more effective option, with a more favorable cytotoxicity profile than the other commonly used irrigation solutions. Clinical outcomes should be studied to determine the most effective agent, concentration, and exposure time for intraoperative irrigation

Aim. Irrigation and debridement with an irrigation solution are essential components of the surgical management of acute and chronic periprosthetic joint infection (PJI). Nevertheless, there is a lack of agreement regarding the most effective solution to use. The aim of the study was to perform a systematic review and meta-analysis of the current literature concerning the efficacy of different irrigation solutions over bacterial biofilm. Method. This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Network meta-analysis (PRISMA-NMA) checklist for systematic reviews and meta-analyses. A comprehensive literature search of PubMed, Cochrane Library, Web of Science and Scopus databases from inception to September 1, 2023. We combined terms related to PJI, biofilm and irrigation solutions studied in vitro. We performed a network meta-analysis to analyze which irrigation solution achieved a higher reduction of colony forming units (CFU) after specific exposure times, always with a maximum of five minutes, replicating intraoperative conditions. Effect-size was summarized with logarithmic response ratio (logRR) and 95% confidence intervals (95% CI). The rank probability for each treatment was calculated using the p-scores. Results. We screened 233 potential sources. Following deduplication, screening and full-text review, four studies with ten irrigation solutions for different duration of exposures were included, always less than five minutes, replicating intraoperative conditions. Solutions were studied over mature biofilms of most frequent bacteria grown over metal, bone cement or polyethylene surfaces. The highest effect was achieved with povidone iodine 10% during 5 minutes (logRR: −12.02; 95% CI: −14.04, −9.99). The best ranked solutions were povidone iodine 10% during five, three and one minute (respective p-scores: 0.977, 0.932, 0.887) and its combination with hydrogen peroxide for 3 minutes (p-score: 0.836). Povidone iodine 0.3% acting for 5 minutes completed the top 5 best ranked solutions in this study (p-score: 0.761). We assumed that there were no inconsistencies in our network because after examining both scenarios, with and without inconsistencies, the results were not significantly different. Conclusions. Our results show that 10% povidone-iodine is the best antiseptic solution when studied in vitro in the context of prosthetic joint infection. However, the included studies did not evaluate the possible cytotoxic effects of these solutions. This should also be taken into account before choosing the most appropriate antiseptic solution

Periprosthetic joint infection (PJI) occurs in 0.2-2% of primary hip and knee arthroplasty and is a leading cause of revision surgery, impaired function, and increased morbidity and mortality. Topical, intrawound vancomycin administration allows for high local drug concentrations at the surgical site and has demonstrated good results in prevention of surgical site infection after spinal surgery. It is a promising treatment to prevent infection following hip and knee arthroplasty. Prior studies have been limited by small sample sizes and the low incidence of PJI. This systematic review and meta-analysis was performed to determine the effectiveness of topical vancomycin for the primary prevention of PJI in hip and knee arthroplasty. A search of Embase, MEDLINE, and PubMed databases as of June 2020 was performed according to PRISMA guidelines. Studies comparing topical vancomycin to standard perioperative intravenous antibiotics in primary THA and TKA with a minimum of three months follow-up were identified. The results from applicable studies were meta-analysed to determine the impact of topical vancomycin on PJI rates as well as wound-related and overall complications. Results were expressed as odds ratios (ORs) and 95% confidence intervals. Nine comparative observational studies were eligible for inclusion. 3371 patients treated with 0.5-2g of topical vancomycin were compared to 2884 patients treated with standard care. Only one of nine studies found a significantly lower rate of PJI after primary THA or TKA (OR 0.09-1.97, p=0.04 for one study, p>0.05 for eight of nine studies), though meta-analysis showed a significant benefit, with vancomycin lowering PJI rates from 1.6% in controls to 0.7% in the experimental group (OR 0.47, p=0.02, Figure 1). Individually, only one of five studies showed a significant benefit to topical vancomycin in THA, while none of seven studies investigating PJI after TKA showed a benefit to topical vancomycin. In meta-analysis of our subgroups, there was a significant reduction in PJI with vancomycin in THA (OR 0.34, p=0.04), but there was no significant difference in PJI after TKA (OR 0.60, p = 0.13). In six studies which reported complication rates other than PJI, there were no significant differences in overall complication rates with vancomycin administration for any study individually (OR 0.48-0.94, p>0.05 for all studies), but meta-analysis found a significant difference in complications, with a 6.7% overall complication rate in controls compared to 4.8% after topical vancomycin, largely driven by a lower PJI incidence (OR 0.76, p=0.04). Topical vancomycin is protective against PJI after hip and knee arthroplasty. No increase in wound-related or overall complication rates was found with topical vancomycin. This meta-analysis is the largest to date and includes multiple recent comparative studies while excluding other confounding interventions (such as povidone-iodine irrigation). However, included studies were predominantly retrospective and no randomized-controlled trials have been published. The limited evidence summarized here indicates topical vancomycin may be a promising modality to decrease PJI, but there is insufficient evidence to conclusively show a decrease in PJI or to demonstrate safety. A prospective, randomized-controlled trial is ongoing to better answer this question. For any figures or tables, please contact the authors directly

Aim. Periprosthetic joint infections (PJI) are increasing due to our elderly population with the need of a joint prosthesis. These infections are difficult to treat, because bacteria form biofilms within one day on the orthopedic implant surface. Notably, most of the current available antibiotics do not penetrate the biofilm or are not active against the sessile forms of bacteria. Therefore, prevention is key. In the current paradigm, bacteria from the skin surface or dermis - such as Staphylococcus aureus, coagulase-negative staphylococci, or Cutibacterium sp. – contaminate the periimplant tissue during surgery. Cutibacterium avidum, which has increasingly been reported in hip PJIs, colonizes the skin in the groin area in 32.3%. We were wondering if standard skin antisepsis before hip arthroplasty is effective to eliminate C. avidum colonization in the surgical field. Method. In a single-center, prospective study, we preoperatively screened all patients undergoing a hip arthroplasty through a direct anterior approach for different skin bacteria in the groin area. Only in patients colonized with C. avidum, we intraoperatively searched for persistent bacterial growth during and after triple skin antisepsis with povidone-iodine/alcohol. For that, we collected skin scrapings after first and third antisepsis and biopsies from the dermis at the surgical incision and evaluated bacterial growth and species. In addition, thin sections of the dermis biopsies were submitted to Fluorescence in situ Hybridization (FISH) using pan-bacteria probe EUB338. Results. From October 2018 until March 2019, 53 patients (47.2% female) were screened. Patients were mainly colonized with coagulase-negative staphylococci (41, 77.4%; 41), C. avidum (12, 22.6%), and Cutibacterium acnes (8, 15.1%). Intraoperative skin antisepsis of patients colonized with C. avidum was ineffective to eliminate any bacteria in 75% (5 out of 7) after the first and 28.6% (2 out of 7) after the third antisepsis. Focusing on C. avidum, antisepsis was ineffective in 43% (3 out of 7) and 14% (1 out of 7), respectively. Dermis biopsies were all culture negative, but FISH showed positive ribosome-rich bacteria in 50%. Conclusions. We show in our ongoing study that the commensal C. avidum resists the standard skin antisepsis and bacteria visually persist in the dermis as demonstrated by FISH technique. Standard skin antisepsis is of limited effectiveness, resulting in a risk for intraoperatively acquired PJIs. Thus, new and more effective techniques to improve skin antisepsis are urgently needed

Among the most critical factors to reducing the risk of infection include the use of pre-incisional antibiotics, appropriate skin preparation with clippers (as opposed to a razor for hair removal) and the use of an alcohol-based skin preparation. Host factors are also likewise critically important including obesity, diabetes, inflammatory arthritis, renal insufficiency, skin disorders and patients who are otherwise immune-compromised. If modifiable risk factors are identified, it would seem reasonable to delay elective surgery until these can be optimised. One other factor to consider is the nutritional status of the patient. In a study of 501 consecutive revisions, we found that serological markers suggestive of malnutrition (albumin, transferrin or total lymphocyte count) were extremely common. Specifically, 53% of patients who presented for treatment of a chronic infection had at least one marker for malnutrition, compared to 33% in the group of patients undergoing revision for an aseptic reason. Malnutrition was found to be an independent risk factor for septic failure (p < 0.001 and OR 2.1). Interestingly, malnutrition was most common among patients of normal weight but was also common among obese patients (so-called “paradoxical” malnutrition). What was more disturbing, however, was that of those patients undergoing an aseptic revision, serum markers of malnutrition were associated with a 6× risk of acute post-operative infection complicating the patient's aseptic revision. We have confirmed this association using the NSQIP database where hypoalbuminemia was associated with a higher risk of infection, pneumonia and readmission. At our center, we also have studied the use of dilute betadine at the end of the case, prior to wound closure, in an attempt to decrease the load of bacteria in the wound. In a retrospective review the prevalence of acute post-operative infection was reduced from just under 1% (18/1862) to 0.15% (1 of 688; p = 0.04). It is critical that the betadine utilised be STERILE and the dilution we use is 0.35% made by diluting 17.5cc of 10% povidone-iodine paint in 500cc of normal saline

Minimizing the risk of periprosthetic joint infection (PJI) is of interest to all surgeons performing hip and knee arthroplasty. Among the most critical factors to reducing the risk of infection include the use of pre-incisional antibiotics, appropriate skin preparation with clippers (as opposed to a razor for hair removal) and the use of an alcohol-based skin preparation. Host factors are also likewise critically important including obesity, diabetes, inflammatory arthritis, renal insufficiency, skin disorders and patients who are otherwise immune-compromised. If modifiable risk factors are identified, it would seem reasonable to delay elective surgery until these can be optimised. One other factor to consider is the nutritional status of the patient. In a study of 501 consecutive revisions, we found that serological markers suggestive of malnutrition (albumin, transferrin or total lymphocyte count) were extremely common in the revision population. Specifically, among patients who presented for treatment of a chronic infection, 53% (67 of 126) had at least one marker for malnutrition. The prevalence of serological markers of malnutrition was lower (33%) in the group of patients undergoing revision for an aseptic reason suggesting that malnutrition was a risk factor for septic failure (p < 0.001 and OR 2.1). Interestingly, malnutrition was most common among patients of normal weight but was also common among obese patients (so-called “paradoxical” malnutrition). What was more disturbing, however, that of those patients undergoing an aseptic revision, serum markers of malnutrition were associated with a 6x risk of acute postoperative infection complicating the patient's aseptic revision. At our center, we also have studied the use of dilute betadine at the end of the case, prior to wound closure, in an attempt to decrease the load of bacteria in the wound. In a retrospective review the prevalence of acute postoperative infection was reduced from just under 1% (18/1862) to 0.15% (1 of 688; p = 0.04). It is critical that the betadine utilised be STERILE and the dilution we use is 0.35% made by diluting 17.5cc of 10% povidone-iodine paint in 500cc of normal saline. Although this is a retrospective review, it does suggest a benefit and we have not seen any problems associated with its use

Minimizing the risk of periprosthetic joint infection (PJI) is of interest to all surgeons performing hip and knee arthroplasty. Among the most critical factors to reducing the risk of infection include the use of pre-incisional antibiotics, appropriate skin preparation with clippers (as opposed to a razor for hair removal) and the use of an alcohol-based skin preparation. Host factors are also likewise critically important including obesity, diabetes, inflammatory arthritis, renal insufficiency, skin disorders and patients who are otherwise immune-compromised. If modifiable risk factors are identified, it would seem reasonable to delay elective surgery until these can be optimised. One other factor to consider is the nutritional status of the patient. In a study of 501 consecutive revisions, we found that serological markers suggestive of malnutrition (albumin, transferrin or total lymphocyte count) were extremely common in the revision population. Specifically, among patients who presented for treatment of a chronic infection, 53% (67 of 126) had at least one marker for malnutrition. The prevalence of serological markers of malnutrition was lower (33%) in the group of patients undergoing revision for an aseptic reason suggesting that malnutrition was a risk factor for septic failure (p < 0.001 and OR 2.1). Interestingly, malnutrition was most common among patients of normal weight but was also common among obese patients (so-called “paradoxical” malnutrition). What was more disturbing, however, that of those patients undergoing an aseptic revision, serum markers of malnutrition were associated with a 6× risk of acute post-operative infection complicating the patient's aseptic revision. At our center, we also have studied the use of dilute betadine at the end of the case, prior to wound closure, in an attempt to decrease the load of bacteria in the wound. In a retrospective review the prevalence of acute post-operative infection was reduced from just under 1% (18/1862) to 0.15% (1 of 688; p = 0.04). It is critical that the betadine utilised be STERILE and the dilution we use is 0.35% made by diluting 17.5 cc of 10% povidone-iodine paint in 500 cc of normal saline. Although this is a retrospective review, it does suggest a benefit and we have not seen any problems associated with its use