The diagnosis of prosthetic-joint infection (PJI) is challenging, as bacteria adhere on implant and form biofilm. Therefore, current diagnostic methods, such as preoperative culture of joint aspirate have limited sensitivity with false-negative results. Aim. To evaluate the performance of measurement synovial fluid (SF) D-lactate (as a pathogen-specific marker) for the diagnosis of PJI and estimate of treatment success. Method. 224 patients undergoing removal knee or hip prosthesis were included in the study between January 2015 and March 2017. 173 patients of this group had aseptic loosening of prosthesis and 87 were diagnosed with PJI. Prior to surgery, synovial fluid routine culture, D-lactate test, leukocyte count and neutrophils (%) were performed for each patient. In order to evaluate a treatment success, the measurement of SF D-lactate before second two-stage exchange procedure (after treatment) was implemented in 30 patients. Diagnosis of PJI was established according to modified Zimmerli criteria. Results. Of 87 patients with infection of prosthetic joints, 61 (70%) had positive synovial fluid cultures, including Staphylococcus spp. (70%), Streptococcus spp. (10%), Enterococcus spp. (6%), Anaerobes (6%), Enterobacteriacae (4%), P. aeruginosa (2%), C. parapsilosis (2%). There was no significant difference in SF D-lactate levels due to different bacterial strains. The optimal D-lactate cut off was 1,2 mmol/l (sensitivity = 98%, specificity = 84%, PPV = 79%, NPV = 98%, AUC 0,99). Concentration of SF D-lactate was significantly higher in patients with PJI compared to aseptic loosening of prosthesis (median (range)) 2.33 (0.99–3.36) vs 0.77 (0.01–2.4), p<0.0001.D-lactate has better sensitivity for diagnosis of PJI (98%), compared to leukocytes (80%) and neutrophils % (89%), p<0.0001). The concentration of D-lactate decreased below cut off within four weeks after revision surgery (after treatment) in all patients except of three, showing relapse of infection (p<0.0001). Conclusions. The measurement of synovial fluid D-lactate demonstrated high analytical performance in the diagnosis of PJI, it is a reliable pathogen specific marker. D-lactate has the best sensitivity as independent diagnostic method and could be implemented for the evaluation of treatment success

The optimum indications for debridement, antibiotics and implant retention (DAIR) are unclear. Previous studies have demonstrated higher success rate of DAIR within one year of the primary arthroplasty. This study aimed to compare the success rate of DAIR vs revision in “early” and “late” infections to provide guidance for clinical decision making. The Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort prospectively recorded PJIs between July 2014 and December 2017 in 27 hospitals. This study included PIANO patients with first time PJIs occurring after primary TKA. Treatment success was defined as the patient being alive, free from further revision and without clinical or microbiological evidence of reinfection at two years follow-up. “Early” and “late” infections were analyzed separately. Univariate analysis compared demographic and disease specific factors between the DAIR and Revision groups. Multivariate binary logistic regression identified whether treatment strategy and other risk factors were associated with treatment success in “early” and “late” infections. In 117 “early” (<1 year) infections, treatment success rate was 56% in the DAIR group and 54% in the revision group (p=0.878). No independent risk factors were associated with treatment outcome on multivariate analysis. In 134 “late” (>1 year) infections, treatment success rate was 34.4% in the DAIR group and 60.5% in the revision group (OR 3.07 p=0.006). On multivariate analysis, revision was associated with 2.47x higher odds of success (p=0.041) when compared to DAIR, patients with at least one significant co-morbidity (OR 2.27, p=0.045) or with Staphylococcus aureus PJIs (OR 2.5, p=0.042) had higher odds of failure. In “late” PJIs occurring >1 year following primary TKA, treatment strategy with revision rather than DAIR was associated with greater success. Patients with significant comorbidities and Staphylococcus aureus PJIs were at higher risk of failure regardless of treatment strategy

Aim. Rifampicin and fluoroquinolone based therapy is generally considered as first-choice targeted oral antimicrobial therapy for staphylococcal prosthetic joint infections (PJI) treated with debridement, antibiotics and implant retention (DAIR). Alternative equally effective antimicrobial strategies are urgently needed due to toxicity and drug-drug interactions that frequently occur with this strategy. Data from recent clinical studies suggests equipoise for other antimicrobial treatment regimens. The objective of the Rifampicin Combination Therapy versus Targeted Antimicrobial Monotherapy in the Oral Antimicrobial Treatment Phase of Staphylococcal Prosthetic Joint Infection (RiCOTTA)-trial is to evaluate whether monotherapy with clindamycin is non-inferior to rifampicin/fluoroquinolone combination therapy in patients with staphylococcal PJI that are treated with DAIR. Method. The RiCOTTA-trial is a multicenter, non-inferiority, open-label, randomized controlled trial evaluating clindamycin versus rifampicin/fluoroquinolone combination therapy in the oral treatment phase in patients with staphylococcal PJI managed with DAIR. The trial is performed in 16 hospitals in the Netherlands. Eligible patients are adults with staphylococcal knee or hip PJI managed by DAIR. Patients are included one to six days before antibiotic treatment is switched from intravenous to oral therapy. Patients with a contraindication for rifampicin, with a megaprosthesis or who receive intravenous antibiotics for more than three weeks after initial debridement are excluded. Primary outcome is treatment success one year after finishing antimicrobial treatment. Success is defined as the absence of: i. Infection related re-surgery, ii. New episode of antibiotic treatment for infection of the index joint after the initial treatment phase of 12 weeks, iii. Ongoing use of antibiotics for the index joint at the end of follow-up, iv. Death. The estimated treatment success of rifampicin combination therapy is 85% and the monotherapy strategy is considered not inferior when the difference in treatment success will be less than 10%. Enrolment of 158 patients per group (316 in total) is needed to confirm non-inferiority of monotherapy with a power of 80%. The trial is currently open for enrolment. The study is approved by the Medical Ethics Committee Leiden, the Hague, Delft, the Netherlands and registered under EU trial number 2022-501620-26-00 in Clinical Trial Information System. Conclusions. Currently, the RiCOTTTA study is the largest randomised clinical trial that compares targeted oral monotherapy with rifampicin combination treatment for staphylococcal PJI. Noninferiority of monotherapy would result in a change in national PJI guidelines and enable clinicians to use a more patient-tailored approach when considering antibiotics for patients during the oral treatment phase of PJI

Prosthetic joint infection (PJI) remains one of the most challenging complications to manage following total joint arthroplasty (TJA). There is a paucity of published data on the management of PJI in smaller, rural hospital settings. In this study, we investigate [1] the success rate of surgical management for PJI following TJA and [2] the microbiology of infecting organisms in this unique geographical environment. We performed a retrospective single-centre study at a rural hospital (Southland Hospital, Invercargill, New Zealand) over a 3-year period (2019 to 2022). All patients presenting with a first episode of PJI fulfilling Musculoskeletal Infection Society criteria after hip or knee arthroplasty were included. All patients had a minimum follow up of 6 months. Treatment success was defined eradication of infection. Twenty-one cases (14 hips and 7 knees) were identified. These were managed with Debridement, antibiotics, and implant retention (DAIR) procedure (n=14, 67%), single-stage revision (n=6, 29%), or long-term suppressive antibiotics (n=1, 4%). Of the DAIR patients, infection recurred in 50% and underwent subsequent revision. Of the single-stage revision patients, 17% failed and underwent subsequent revision. The overall success rate was 90%. Methicillin-sensitive Staphylococcus aureus (MSSA) was the most isolated pathogen (57%,) with no methicillin-resistance Staphylococcus aureus (MRSA) identified. Overall, 90% of infecting organisms were cefazolin sensitive. These results suggest that management of PJI is a safe and viable treatment option when performed in a rural hospital setting, with comparable treatment success rates to urban centres. The incidence of MRSA is low in this setting. Rates of antibiotic resistance were relatively low and most organisms were sensitive to cefazolin, the routine antibiotic used in prophylaxis

We investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. We aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. We also compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes. Skeletally mature female Wistar rats were implanted with Staphylococcus epidermidis- contaminated polyetheretherketone (PEEK) screws in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. Bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels on days 0, 6, 20, and 28. Combination antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p<0.0001 on day 14 periosteal thickness) during early infection compared to the control group. Short- term celecoxib treatment showed similar radiological results without a reduction in treatment success (88.9%). No differences in the inflammatory markers were observed. Our findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy

Aim. In this study we investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. Specifically, we aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. In addition, we compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes. Method. Skeletally mature female Wistar rats were implanted with Staphylococcus epidermidis-contaminated polyetheretherketone (PEEK) screws (1.5 × 10. 6. CFU per screw) in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. After implantation, bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels at four time points (day 0, 6, 20, and 28). Results. The combination of antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p<0.0001 on day 14 periosteal thickness) during the early post-infection period compared to the control group. Short-term celecoxib treatment showed similar radiological results, however, there was no significant reduction in treatment success in the celecoxib group (88.9%). No differences in the selected inflammatory markers were observed. Conclusion. Our findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy. This study suggests that celecoxib may be a useful addition to the multimodal approach to pain management in orthopaedic device-related infections

Aim. The purpose of this study is to report the overall infection control rate and prognostic factors associated with acute, hematogenous and chronic PJIs treated with DAIR. Methods. All DAIR procedures performed at 2 institutions from 2009 to 2018 (n=104) were reviewed and numerous data were recorded, including demographics, preoperative laboratory tests, Charleston Comorbidity Index, surgical information and organism culture results. Treatment success was defined according to the criteria reported by Diaz-Ledezma. A multivariable analysis was utilized to identify prognostic factors associated with treatment and a Kaplan-Meier survival analysis was used to depict infection control rate as a function of time. Results. The overall treatment success rate in the current cohort of patients was 67.3% at a median 38.6 (23.5–90.7) months follow-up. Patients with a duration of infectious symptoms greater than 10 days were more likely to fail (P=0.035, odds ratio 8.492, 95% confidence interval 1.159–62.212). There was no difference among acute, hematogenous and chronic infections in terms of failure rate even when time was considered (p=0.161). Conclusion. With careful patient selection, DAIR is a reasonable treatment option for PJI and its use in the setting of chronic infection does not appear to be a contraindication. Performing the DAIR procedure within 10 days of the presentation of symptoms had higher rates of treatment success

Aim. The treatment of fracture-related infections (FRI) focuses on obtaining fracture healing and eradicating infection to prevent osteomyelitis. Treatment guidelines include removal, exchange, or retention of the implants used according to the stability of the fracture and the time from the infection. Infection of a fracture in the process of healing with a stable fixation may be treated with implant retention, debridement, and antibiotics. Nonetheless, the retention of an intramedullary nail is a potential risk factor for failure, and it is recommended to exchange or remove the nail. This surgical approach implies additional life-threatening risks in elderly fragile hip fracture patients. Our study aimed to analyze the results of implant retention for the treatment of infected nails in elderly hip fracture patients. Methods. Our retrospective analysis included patients 65 years of age or older with an acute fracture-related infection treated with implant retention from 2012 to 2020 in 6 Spanish hospitals with a minimum 1-year follow-up. Patients that required open reduction during the initial fracture surgery were excluded. Variables included in our analysis were patient demographics, type of fracture, date of FRI diagnosis, causative microorganism, and outcome. Treatment success was defined as fracture healing with infection eradication without the need for further hospitalization. Results. A total of 48 patients were identified. Eight patients with open reduction were excluded and 11 did not complete a 1-year follow-up. Out of the 29 remaining patients, the mean age was 81.5 years, with a 21:9, female to male ratio. FRI was diagnosed between 10 and 48 days after initial surgery (mean 26 days). Treatment success was achieved in 24 patients (82.7%). Failure was objectivated in polymicrobial infections or infections caused by microorganisms resistant to antibiofilm antibiotics. Seven patients required more than one debridement with a success rate of 57%. Twelve patients had an infection diagnosed after 21 days from the initial surgery and implant retention was successful in all of them. Conclusion. Our results suggest implant retention is a valid therapeutic approach for fracture-related infection in elderly hip fracture patients treated by closed reduction and intramedullary nailing

Aim. Culture negative (CN) prosthetic joint infections (PJI) account for approximately 10% of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJI within a large prospective cohort study, and to compare their characteristics and outcomes with culture positive cases. Methods. The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, binational, multicentre observational cohort study conducted at 27 hospitals between July 2014 and December 2017. We compared baseline characteristics and outcomes of all patients with culture negative (CN) prosthetic joint infection (PJI) from the PIANO cohort with culture positive (CP) cases. “Treatment success” was defined as absence of clinical or microbiological signs of infection, no need for ongoing antibiotics, and no need for revision or resection arthroplasty since the end of the initial treatment. We also describe PJI diagnostic criteria in the CN cohort and apply internationally recognised PJI diagnostic guidelines. Results. Of the 650 patients eligible for inclusion, 55 (8.5%) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female [32 (58.2%) vs 245 (41.2%); p=0.02], involve the shoulder joint [5 (9.1%) vs. 16 (2.7%); p=0.03] and have a lower mean C-reactive protein (142 mg/L vs. 187 mg/L; p=0.02). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (aOR 3.78; 95%CI 1.65 – 8.67). Of the 55 CN cases meeting Infectious Diseases Society of America (IDSA) diagnostic criteria, 45 (82%) met European Bone and Joint Infection Society (EBJIS) criteria (probable or definite) and 39 (71%) met the 2013 Musculoskeletal Infection Society (MSIS) criteria. Conclusions. Culture negativity is an independent predictor of treatment success in PJI. It is unclear whether this is because some of them are not actually infections, or for other reasons such as lower bacterial load or earlier effective antibiotic treatment. Diagnostic criteria for PJI vary substantially in their sensitivity, with MSIS criteria being the least sensitive. Acknowledgements. This work is being presented on behalf of the broader PIANO investigators and the Australasian Society for Infectious Diseases Clinical Research Network. The PIANO study received seed funding from Heraeus Medical and the John Hunter Hospital Charitable Trust Fund

Aim. We aimed to assess the incidence and the outcome of Gram-negative prosthetic-joint infections (PJI) in 3 international tertiary hospital. Method. We included patients with Gram-negative PJI at Humanitas Clinical and Research Hospital (Milan, Italy), Centre Hospitalier Universitaire Vaudois (Lausanne, Switzerland) and Hospital Parc de Salut Mar (Barcelona, Spain) between 2014 and 2018 in a retrospective cohort. We described the treatment's success rate according to Gram-negative species and type of surgical procedure. Results. In the present cohort we have 780 PJI out of which 71 (9.1%) were caused by Gram-negative bacteria (polymicrobial infection 30%, Escherichia coli 25%, Pseudomonas aeruginosa 20%, Proteus spp. 4%, Klebsiella spp. 3%, Morganella morganii 3%, Enterobacter 3%, others 12%). Gram-negative PJI were more common in females (60%) than males (40%). Sixty percent had a hip infection, 40% a knee infection, the median age was 74 years and the median ASA score was 3. It was a chronic infection in 60% of the cases and an acute one in 40%. Two-step exchange was performed in 55%, débridement and retention (DAIR) in 30%, one-step exchange in 11% and implant removal without replacement in 4% of the patients. The overall treatment success rate was 89%. The success rate was better for two-step exchange (95%) compared to DAIR (81%) and one-step exchange (87%) (p=0.068). The median antibiotic duration was 68 days and ciprofloxacin was used in 70% of the cured patients versus in 88% of the failures (p=0.388). Infections caused by Escherichia coli were associated with a lower success rate (83%) especially compared to Pseudomonas aeruginosa (93%) and polymicrobial infections (90%) (p=0.358). Finally, the success rate was better in knee PJI compared to hip PJI (97% versus 83%, p=0.121) and in females compared to males (93% versus 82%, p=0.121). Conclusions. The treatment's success of Gram-negative PJI is comparable to reported rates for all bacteria. However, our results suggest that surgical management with two-step exchange might be useful in selected patients’ groups such as those with Escherichia coli PJI. Moreover, ciprofloxacin use seems not to improve cure rate

Prosthetic joint infections (PJI) are devastating complications. Our knowledge on hip fractureassociated hemiarthroplasty PJI (HHA-PJI) is limited compared to elective arthroplasty. The goal of this study was to describe the epidemiology, risk factors, management, and outcomes for HHA-PJI. A population-based (465,000) multicentre retrospective analysis of HHAs between 2006-2018 was conducted. PJI was defined by international consensus and treatment success as no return to theatre and survival to 90 days after the initial surgical management of the infection. Univariate, survival and competing risk regression analyses were performed. 1852 HHAs were identified (74% female; age:84±7yrs;90-day-mortality:16.7%). Forty-three (2.3%) patients developed PJI [77±10yrs; 56% female; 90-day-mortality: 20.9%, Hazard-Ratio 1.6 95%CI 1.1-2.3,p=0.023]. The incidence of HHA-PJI was 0.77/100,000/year and 193/100,000/year for HHA. The median time to PJI was 26 (IQR 20-97) days with 53% polymicrobial growth and 41% multi-drug resistant organisms (MDRO). Competing risk regression identified younger age [Sub-Hazard-Ratio(SHR) 0.86, 95%CI 0.8-0.92,p<0.001], chronic kidney disease (SHR 3.41 95%CI 1.36-8.56, p=0.01), body mass index>35 (SHR 6.81, 95%CI 2.25-20.65, p<0.001), urinary tract infection (SHR 1.89, 95%CI 1.02-3.5, p=0.04) and dementia (SHR 9.4, 95%CI 2.89-30.58,p<0.001) as significant risk factors for developing HHA-PJI. When infection treatment was successful (n=15, 38%), median survival was 1632 days (IQR 829-2084), as opposed to 215 days (IQR 20-1245) in those who failed, with a 90-day mortality of 30%(n=12). There was no significant difference in success among debridement, excision arthroplasty or revision arthroplasty. HHA PJI is uncommon but highly lethal. All currently identified predictors are non-modifiable. Due to the common polymicrobial and MDRO infections our standard antibiotic prophylaxis may not be adequate HHA-PJI is a different disease compared to elective PJI with distinct epidemiology, pathogens, risk factors and outcomes, which require targeted research specific to this unique population

Aim. Antimicrobial suppression has shown to significantly improve treatment success of streptococcal periprosthetic joint infection (PJI) compared to 12-week standard antimicrobial therapy, however, only short-term follow-up was investigated. In this study we assessed the impact of suppression on the long-term outcome of streptococcal PJI. Method. Consecutive patients with streptococcal PJI (defined by EBJIS criteria) treated 2009–2021 were prospectively included and allocated into standard and suppression (> 6 months) treatment group. Infection-free survival was assessed with Kaplan-Meier-method and compared between the groups with log rank test. Rates of infection-free, streptococcal infection-free and relapse-free status as well as tolerability of suppression were assessed. Results. Sixty-three PJI episodes (36 knee, 26 hip and one shoulder prosthesis) of patients with a median age of 70 (35–87) years were included. Twenty-seven (43%) were females. Predominant pathogens were S. agalactiae (n=20), S. dysgalactiae (n=18) and S. mitis/oralis (n=13). The main surgical procedures used were two-stage exchange (n=35) and prosthesis retention (n=21). Standard 12-week treatment was administered in 33 patients and suppression in 30 patients, of whom 10 had ongoing suppression and 20 had discontinued antibiotics at time of follow-up. Used oral antibiotics for suppression were amoxicillin (n=29), doxycycline (n=5) and clindamycin (n=2); 6 patients changed antibiotic substance due to side effects. The median follow-up time was 3.9 (0.3–13.3) years. Infection-free survival after 7.5 years was 38% with standard treatment and 62% with suppression (p=0.038). Of all failures, 52% (14/27) were due to streptococci. Suppression was effective in preventing streptococcal infection for the duration of antimicrobial treatment, however, after discontinuation relapses or new infections due to streptococci occurred in 5/20 (25%) patients and infection with any Streptococcus spp. was observed in 9/19 (47%) failures with standard treatment, 5/6 (83%) failures after discontinuing suppression and none during suppression. All failures in patients with ongoing suppression were caused by gram-negative rods. Conclusion. At long-term follow-up, the success rate was superior with suppression compared to standard treatment. Most failures after stopping suppression were caused by streptococci, whereas failures under suppression were caused by aerobic gram-negative rods

Aim. Treatment of enterococcal periprosthetic joint infections (PJI) is challenging due to heterogeneous pathogenesis, non-standardized management strategies and lack of biofilm-active antibiotics. Previous studies report treatment success from 50–76%. We evaluated the characteristics and outcome of enterococcal PJI, in particular the influence of antimicrobial treatment regimens. Method. Consecutive patients with enterococcal PJI treated at two specialized orthopaedic institutions were retrospectively included from 2010 to 2017. PJI was defined by the proposed European Bone and Joint Infection Society (EBJIS) criteria. Adequate antimicrobial treatment was considered when the antibiotic was appropiate for the treatment of enterococcal bone infections (activity, dose, oral bioavailability, bone penetration). The treatment success (defined as no relapse of enteroccal infection) and clinical success(i.e. infection-free status) was evaluated and compared using Fishers exact test. Results. We included 75 episodes with enterococcal PJI, involving 41 hip, 30 knee, 2 elbow, 1 shoulder prosthesis. The median patient age was 76 years (range, 30–90 years), 48 (64%) were female. The infection occurred perioperatively in 61 episodes (81%), haematogenously in 13 (17%) and by contiguous spread in 1 case. Sinus tract was present in 16 patients (21%), predominantly in polymicrobial compared to monomicrobial infections (13 vs. 3 episodes, p= 0.01). Preoperative serum C-reactive protein level was elevated in 63/75 patients (84%) and synovial fluid leukocyte count was increased in 25/29 patients (86%). Enterococci grew in synovial fluid in 76%, in periprosthetic tissue in 78% and in sonication fluid in 73% of patients. Predominantly, E. faecalis was identified (n=64), followed by E. faecium (n=10) and E. casseliflavus (n=1); mixed infections were diagnosed in 38 patients (51%). Two-stage prosthesis exchange was performed in 44 (59%), debridement and retention in 13 (17%), resection arthroplasty in 11 (15%) and one-stage exchange in 10 patients (13%). Of 66 patients with available follow-up data (median, 31.8 months; range, 0.3–83.3 months), the treatment success was 85% (56/66), however, clinical success was only 68% (45/66). Treatment success was similar in monomicrobial and polymicrobial infections. Adequate antimicrobial treatment was associated with significant better outcome (91% vs. 38%, p=0.002). Treatment with fosfomycin (19/20, 95%) and combination therapy (45/50, 90%) was associated with better outcome, however, did not reach statistical significance (p >0.05). Conclusions. The treatment outcome of enterococcal PJI was high (85%), however, a second episode of PJI caused by a new pathogen was common in the later course. Adequate antimicrobial treatment was the only significant factor associated with better treatment success

Aim. Rifampin is considered as the antibiotic corner stone in the treatment of acute staphylococcal periprosthetic joint infections (PJI). However, if, when, and how to use rifampin has been questioned. We evaluated the outcome of patients treated with and without rifampin, and analysed the influence of timing, dose and co-antibiotic. Method. Acute staphylococcal PJIs treated with surgical debridement between 1999 and 2017, and a minimal follow-up of 1 year were evaluated. Treatment failure was defined as the need for any further surgical procedure related to infection, PJI-related death, or the need for suppressive antimicrobial treatment. Results. A total of 669 patients were analysed. Treatment failure was 32.2% (131/407) in patients treated with rifampin and 54.2% (142/262) in whom rifampin was withheld (P < 0.001). The most prominent effect of rifampin was observed in knees (treatment failure 28.6% versus 63.9%, respectively, P < 0.001). The use of rifampin was an independent predictor of treatment success in the multi-variate analysis (OR 0.30, 95% CI 0.20 – 0.45). In the rifampin group, the use of a co-antibiotic other than a fluoroquinolone (OR 7.73, 95% CI 4.26 – 14.0) and the start of rifampin within 5 days after surgical debridement (OR 1.88, 95% CI 1.05 – 3.35) were predictors of treatment failure. Clindamycin demonstrated similar efficacy as co-antibiotic. The dosing of rifampin had no effect on outcome. Conclusions. Our data supports the use of rifampin in acute staphylococcal PJIs treated with surgical debridement, particularly in knees. Immediate start of rifampin after surgical debridement should probably be discouraged

Aim. Data on Prosthetic joint infection (PJI) caused by multi-drug resistant (MDR) or XDR (extensively drug resistant) Gram negative bacteria (GNB) are limited. Treatment options are also restricted. We conducted a multi-national, multi-center assessment of clinical data and factors of outcome for these infections. Method. PJI were defined upon international guidelines. Data from 2000–2015 on demographics, clinical features, microbiology, surgical treatment and antimicrobial therapy was collected retrospectively. Factors associated with treatment success were evaluated by logistic regression analysis. Results. A total of 133 PJI were evaluated. Female (n=84, 61.4%) and the elderly [mean age (+/-SD) 73 (12.7)] predominated. Diabetes mellitus was the most frequent comorbidity (n=42,32.1%) followed by rheumatoid arthritis (n=14,10.7). Most PJI were early infections (84.4 %). XDR accounted for 23 cases; half of them due to Pseudomonas aeruginosa. Prevalence of MDR or XDR GNB was not different between early and late PJIs (p=0.114). Overall, P.aeruginosa (n=25, 19.1%) was followed by Klebsiella spp (n=23,17.6%) and Enterobacter spp (n=22,16.8%). PJI was located at the hip (n=85 65.6%), knee (n=41,31.3%), shoulder (n=3,2.3%) and ankle (n=1, 0.8%). Clinical characteristics included soft tissue infection (66.4%), pain (51.1%), fever (32.1%) and sinus tract(29.8%). Surgery for PJIs consisted of DAIR (debridement, antibiotics and implant retention), (n=64, 49.6%), followed by explantation of the arthroplasty (n=32, 24.8%), two-stage revision (n=16, 12,4%), one stage revision (n=9, 7%), arthrodesis (n=2, 1.6%). Median duration of antibiotic therapy was 51 days (IQR 25–75: 40–90 days). Cure after treatment was assessed in 78 patients (58.6%). No-DAIR surgical procedures in PJIs were more likely to be successful compared to DAIR surgery (75.8% vs 50%, OR 3.13, 95% CI:1.47–6.70, p=0.003)both in early or late infections. Conclusions. PJI by MDR/XDR GNB affects female, the elderly with comorbidities and previous surgery for PJI. P.aeruginosa is frequent, mostly XRD. No-DAIR procedures have higher probability of treatment success than DAIR even in early infection. Despite surgery and long-term antimicrobial administration, treatment success was less than 60%, probably reflecting the lack of effective treatment options

Aim. Fungal orthopaedic infections most commonly affect people with complex surgical histories and existing comorbidities. Recurrence and re-infection rates are high, even with optimal surgical and systemic antifungal treatment. AmBisome liposomal amphotericin B has been suggested for local antifungal therapy, as an adjunctive treatment for fungal osteoarticular infections. Few case series have examined its clinical use when combined with polymethylmethacrylate cement PMMA), or with absorbable local antibiotic carriers. We aimed to evaluate the clinical use of local antifungal therapy with AmBisome liposomal amphotericin B (ABlaB), including tolerated doses, serious adverse events, and treatment outcomes. Method. A retrospective cohort of all patients treated with local antifungal therapy with ABlaB between January 2016 and January 2021 in a specialist orthopaedic hospital was identified using pharmacy records. Renal function, serious adverse events during treatment, surgical outcomes including spacer fracture and infection recurrence, were identified from electronic clinical records. The project was approved by the Institutional Review Board (clinical audit 6871). Results. 13 operations involving local antifungal therapy with ABlaB, in 12 patients, were identified. Eleven were infected with Candida species and one with Aspergillus. Mean follow-up was 22 months (range 4–46). Ten first stage arthroplasty revisions, 2 second stage arthroplasty revisions, and one debridement and removal of metalwork for fracture-related infection were performed. Locally implanted doses of ABlaB ranged from 100mg to 3600mg (50–400mg per 40g mix of PMMA). Six patients received ABlaB in absorbable antibiotic carriers containing calcium sulphate. This was noted to delay carrier setting. Patients were also given systemic antifungal therapy. No patients experienced serious adverse events related to toxicity from local antifungal therapy with ABlaB. There were no spacer fractures. Overall treatment success was 54% at final follow-up, although there were no recurrent fungal infections identified in patients experiencing treatment failure. Conclusions. Local antifungal therapy with liposomal amphotericin B, when combined with surgery and systemic therapy, appears to be a safe and well tolerated intervention in the management of complex fungal osteoarticular infections

Many studies report the incidence and prevalence of surgical site infections (SSIs) following open fractures; however, there is limited information on the treatment and subsequent outcomes of superficial SSIs in open fracture patients. There is also a lack of clinical studies describing the prognostic factors that are associated with failure of antibiotic treatment (non-operative) for superficial SSI. To address this gap, we used data from the FLOW (Fluid Lavage in Open Fracture Wounds) trial to determine how successful antibiotic treatment was for superficial SSIs and to identify prognostic factors that could be predictive of antibiotic treatment failure. This is a secondary analysis of the FLOW trial dataset. The FLOW trial included 2,445 operatively managed open fracture patients. FLOW participants who had a non-operatively managed superficial SSI diagnosed in the 12 months post-fracture were included in this analysis. Participants were grouped into two categories: 1) participants whose superficial SSI resolved with antibiotics alone and 2) participants whose SSI did not resolve with antibiotics alone (defined as requiring surgical management or SSI being unresolved at final follow-up (12-months post-fracture for the FLOW trial)). Antibiotic treatment success and the date when this occurred was defined by the treating surgeon. A logistic binary regression analysis was conducted to identify factors associated with superficial SSI antibiotic success. Based on biologic rationale and previous literature, a priori we identified 13 (corresponding to 14 levels) potential factors to be included in the regression model. Superficial SSIs were diagnosed in168 participants within 12 months of their fracture. Of these, 139 (82.7%) had their superficial SSI treated with antibiotics alone. The antibiotic treatment was successful in resolving the superficial SSI in 97 participants (69.8%) and unsuccessful in resolving the SSI in 42 participants (30.2%). We found that superficial SSIs that were diagnosed later in follow-up were associated with failure of treatment with antibiotic alone (Odds ratio 1.05 for every week in diagnosis delay, 95% Confidence Interval 1.004–1.099; p=0.03). Age, sex, fracture severity, fracture pattern, wound size, time from injury to initial surgical irrigation and debridement were not associated with antibiotic treatment failure. Our secondary analysis of prospectively collected FLOW data found antibiotics alone resolved superficial SSIs in 69.8% of patients diagnosed with superficial SSIs. We also found that superficial SSIs that were diagnosed earlier in follow-up were associated with successful treatment with antibiotics alone. This suggests that if superficial SSIs are diagnosed and treated promptly, there is a higher probability that they will resolve with antibiotic treatment

Aim. Calcaneal osteomyelitis is an uncommon and challenging condition. In this systemic review we aim to analyse the concomitant use of bone debridement and soft tissue management for patients diagnosed with calcaneal osteomyelitis. Method. A complete computerised and comprehensive literature search of Pubmed and Cochrane database was undertaken from January 2000 to October 2018. During the review, studies were screened for information about the surgical and antimicrobial treatment, the complications, the reinfection rate and the functional outcome of patients with calcaneal osteomyelitis. Results. Of the 20 studies included, seven (35%) described bone treatment only, six (30%) soft tissue treatment only, five (25%) soft tissue and bone treatment, and two (10%) focused on prognostic factors and differences in outcomes between diabetic and non-diabetic patients. In the studies with bone treatment only, infection recurrence ranged from 0 to 35% and the amputation rate from 0 to 29%. If soft tissue coverage was also needed, both the reinfection rate and amputation rate ranged from 0 to 24%. Studies presenting the functional status showed preservation or even improvement of the preoperative ambulatory status. Conclusions. Calcaneal osteomyelitis is difficult to treat. A multidisciplinary approach involving orthopaedic surgeons, plastic surgeons and infectious disease physicians is necessary for treatment success. Based on the localisation and size of the bone and soft tissue defect, decision for surgical treatment should be made

Aim. Treatment success of debridement, antibiotics and implant retention (DAIR) is in early periprosthetic joint infection (PJI) is largely dependent on the presence or absence of a mature biofilm. In what time interval a mature biofilm develops is still unclear, and therefore, the time point at which DAIR should be disrecommended remains to be established. This large multicenter trial evaluated the failure rates of DAIR for different time intervals from index arthroplasty to DAIR in early PJI. Method. We retrospectively evaluated patients with early PJI treated with DAIR between 1996 and 2016. Early PJI was defined as a PJI that developed within 90 days after index arthroplasty. Patients with hematogenous infections, arthroscopic debridements and a follow-up less than one year were excluded. Treatment failure was defined as 1) any further surgical procedure related to infection 2) PJI-related death, or 3) long-term suppressive antibiotics, all within one year after DAIR. Results. A total of 769 patients were analyzed. Treatment failure occurred in 294 patients (38.2%), and was highest in the early (0–2 weeks) and late (6–12 weeks) post-surgical course: 0–2 weeks: 42.0% (95/226); 2–4 weeks: 37.8% (143/378); 4–6 weeks: 29.0% (29/100), and 6–12 weeks: 41.5% (27/65). Exchange of modular components was performed to a lesser extent in the early compared to the late post-surgical course (40.7% vs 63.2%, p<0.001). The percentage of positive cultures obtained during DAIR decreased according to the time interval from index arthroplasty to DAIR: 0–2 weeks: 88.6%; 2–4 weeks: 86.5%; 4–6 weeks: 75.1%; and 6–12 weeks: 63.2%, p<0.001. The causative microorganisms and the duration of symptoms were comparable between groups (6.7 days, SD ± 5.9, p=0.135). Conclusions. Although failure rates increase when a DAIR is performed more than six weeks after index arthroplasty, DAIR is still a viable treatment option in these patients in case DAIR is performed as soon as symptoms of infections arise and modular components can be exchanged

Background. DAIR is an attractive treatment for PJI. The purpose of this study is to determine predictive factors of failure. Materials and Methods. We reviewed all DAIR procedures for hip PJI performed between 2002–2017 (n=69). Data recorded included all factors correlated with treatment failure. KLIC score and an adapted McPherson score (sum of three criteria where the lower score is three for 3 A and the higher is 9 for 3 C) were analyzed. Results. Infection eradication for early PJI (< 4 weeks) was achieved in 68% of patients and was correlated with treatment success (p=0.01). Success rate was only 37.5% in hematogenous infection and 28% in late infection. KLIC score (p=0.036), McPherson adapted score (threshold value 5.5/9) (p=0.01), CRP (with a cut-off value at 73.5 mg%) (p=0.025) and late PJI (p=0.031) were significantly predictive of failure treatment. For the KLIC score, patients with a score of ≤2, >2–3.5, >4–6.5, ≥7, respectively obtained a rate of failure of 33.3%,60%,71% and 100%. We have established an equation in order to predict failure treatment. This tool predicts treatment failure when Logit P (equation result) is >0.476 with a sensitivity of 80% and a specificity of 83% (p = 0.05). Conclusions. KLIC and adapted McPherson scores predict outcome of DAIR and should help making the decision in PJI treatment. Tsang et al, demonstrates that symptoms lasting for less than 7 days represent a significant threshold. Despite 80% of our patients operated within 7 days, the analysis wasn't significant. It seems that a DAIR procedure done promptly is not the only condition required for success and some other factors influence the outcome of treatment. Logit P = 0.376 − (0.0533 ∗ Kidney failure) + (0.933 ∗ Age) + (0.640 ∗ BMI) + (1.111 ∗ Tobacco) + (0.031 ∗ Fistula) + (0.164 ∗ Deep infection) − (0.366 ∗ Revision) − (2.684 ∗ Exchange of the modular component) − (2.685 ∗ Early PJI) + (1.243 ∗ Hematogen PJI) + (0.127 ∗ Polymicrobial PJI) − (0.309 ∗ Staphylococcus aureus) + (0.393 ∗ MRSA) + (0.907 ∗ Resistance to quinolons/rifampicin) + (3.789 ∗ CRP >73,5mg/L) − (2.578 ∗ Onset of symptoms > 7days)