Aims

This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment.

Aims. Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm. Methods. We conducted an in vitro study examining the efficacy of several antiseptic solutions against clinically relevant microorganisms. We tested antiseptic irrigants against nascent (four-hour) and mature (three-day) single-species biofilm created in vitro using a drip-flow reactor model. Results. With regard to irrigant efficacy against biofilms, Povidone-iodine treatment resulted in greater reductions in nascent MRSA biofilms (logarithmic reduction (LR) = 3.12; p < 0.001) compared to other solutions. Bactisure treatment had the greatest reduction of mature Pseudomonas aeruginosa biofilms (LR = 1.94; p = 0.032) and a larger reduction than Vashe or Irrisept for mature Staphylococcus epidermidis biofilms (LR = 2.12; p = 0.025). Pooled data for all biofilms tested resulted in Bactisure and Povidone-iodine with significantly greater reductions compared to Vashe, Prontosan, and Irrisept solutions (p < 0.001). Conclusion. Treatment failure in PJI is often due to failure to clear the biofilm; antiseptics are often used as an adjunct to biofilm clearance. We tested irrigants against clinically relevant microorganisms in biofilm in vitro and showed significant differences in efficacy among the different solutions. Further clinical outcome data is necessary to determine whether these solutions can impact PJI outcome in vivo. Cite this article: Bone Joint J 2021;103-B(5):908–915

Intraoperative histology has a high specificity and sensitivity to identify prosthetic joint infection. However, the usefulness of this technique according to the type of microorganism isolated in the periprosthetic tissue has not previously been studied. Frozen sections and cultures from periprosthetic tissue of 38 revision arthroplasties performed due to prosthetic joint infection were retrospectively reviewed. Frozen sections were evaluated according to Mirras’ criteria (adapted by Feldman). Culture was considered positive when the same microorganism was isolated in at least 2 samples or the presence of pus around the prosthesis. Coagulase-negative staphylococci (CNS) was the aetiology in 13 cases, Gram-negative bacilli in 8, S. aureus in 7, Candida sp and Peptococcus sp in 2 and Enterococcus sp, S.pneumoniae and in 1 case each one. No microorganism was isolated in 4 cases. Frozen sections revealed more than 5 neuthrophils per high power field (forty times) in at least five fields in all cases except in 2 out of 13 caused by CNS (15.3%). A revision of the articles that provided information on the aetiology and the histology supports the findings of our study. In conclusion, frozen section using Feldman’s criteria had a 15.3% of false negative cases when CNS was the aetiology of the prosthetic joint infection

Aims. Currently, the most common approach for the management of a chronic PJI is a Two-Stage Replacement; because of success rates exceeding 90% when using an antibiotic impregnated cement spacer. Reliable information regarding the etiologic microorganism and its sensitivities is essential to select the antimicrobial therapy that should be used locally in the bone cement spacer during the first stage surgery as well as to select the appropriate microbiological systemic agent. Diagnostic algorithms focus to the importance of joint aspiration cultures although in the modern literature, preoperative joint aspiration has a broad range of values of sensitivity and the proportion of “dry-aspirations” is not well assessed. This low sensitivity of aspiration fluid samples in chronic-PJI is partly attributable to the fact that the majority of the microorganisms in these infections grow in biofilms attached to the implant. We have developed this biopsy technique in an effort to improve the identification rates of the causative organism. Materials and methods. A sample is harvested through a 4 mm bone trephine and the target is the bone-prosthesis gap. We have compared the results of preoperative PIB with the results of cultures from intra-operative tissue collected during the first stage surgery. In both cases a prolonged culture protocol (10 days) in enrichment media was used. On the basis of this relation, sensitivity, specificity, positive and negative predictive values and accuracy were calculated. Results. Twenty-four PIB were done on the 24 patients (10 hips and 14 knees) who subsequently underwent two-stage revision surgery because of high suspicion of PJI between January 2007 and December 2009. A retrospective analysis was performed in these 24 patients (13 women and 11 men) in the mean age of 70 years (from 63 to 88 years old). Nineteen of the cases were primary and 5 were revision arthroplasty. Nineteen patients (79%) were positive for infection from operative tissue cultures. The sensitivity was 0.79 (95% CI, 0.54–0.93); the specificity was 0.80 (95% CI, 0,30–0.99), the positive predictive value was 0.94 (95% CI, 0.67–0.99), the negative predictive value was 0.50 (95% CI, 17.5–82.5) and the accuracy was 0.79. Conclusion. PIB is a useful test to, preoperatively, isolate the infecting bacteria. The values of sensitivity, specificity and accuracy are on the average of the currently published with joint aspiration or biopsy samples cultures. Although comparative study is necessary we believe that the PIB could be useful in cases with high suspicion of PJI and negative joint aspiration cultures and in cases where no fluid is aspired from the joint, in order to preoperatively isolate the infecting bacteria

Aims. The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld. Methods. A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. Results. None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). Conclusion. When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or molecular techniques. Cite this article: Bone Joint J 2022;104-B(1):183–188

Aims

Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

Introduction

Infection rates following arthroplasty surgery are reported between 1–4%, with considerably higher rates in revision surgery. The associated costs of treating infected arthroplasty cases are over 4 times the cost of primary arthroplasties, with significantly worse functional and satisfaction outcomes. In addition, multiple antibiotic resistant bacteria are developing, so to reduce the infection rates and costs associated with arthroplasty surgery, new preventative methods are required. HINS-light is a novel blue light inactivation technology which kills bacteria through a photodynamic process, and is proven to have bactericidal activity against a wide range of species. The aim of this study was to investigate the efficacy of HINS-light for the inactivation of bacteria isolated from infected arthoplasty cases.

Aim

Propionibacterium acnes is a skin commensal colonizing the deeper structures of the pilous bulb. It is responsible for 5–10% of lower limb prosthetic joint infections (PJI) but accounts for as many as 50% of shoulder arthroplasty infections. P. acnes PJIs characteristically feature limited systemic inflammation, limited polymorphonuclear infiltration and clinical signs compatible with aseptic loosening. All current microbiological definitions of PJI require two or more identical commensal isolates to be recovered from the same procedure to diagnose PJI to increase specificity and rule out contamination. Whereas the antimicrobial susceptibility patterns of coagulase negative staphylococci are highly polymorphic and commonly allow the ready distinction of unrelated strains, P. acnes shows a highly stereotypical susceptibility profile and it is impossible to phenotypically assess the clonal relationship of isolates. In order to determine the clonal relationship of multiple P. acnes isolates recovered from arthroplasty revisions, we analyzed by multi-locus sequence typing (MLST) P. acnes isolates grown from PJI in a reference center for bone and joint infection.

Aims. This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool. Methods. Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures. Results. The JI panel detected microorganisms in 7/48 (14.5%) and 15/67 (22.4%) cases related to UNCs and SPCs, respectively, but not in cases of UPCs. The correlation between JI panel detection and infection classification criteria for early/late acute and chronic PJI was 46.6%, 73%, and 40%, respectively. Overall, the JI panel identified 12.6% additional microorganisms and three new species. The JI panel pathogen identification showed a sensitivity and specificity of 41.4% (95% confidence interval (CI) 33.7 to 49.5) and 91.1% (95% CI 84.7 to 94.9), respectively. In total, 19/195 (9.7%) could have been managed differently and more accurately upon JI panel evaluation. Conclusion. Despite its microbial limitation, JI panel demonstrated clinical usefulness by complementing the traditional methods based on multiple cultures, particularly in PJI with unclear microbiological results. Cite this article: Bone Joint Res 2024;13(7):353–361

Background. Data regarding the diagnostic value of ultrasound (US)-determined fluid film and joint aspiration prior to revision total hip arthroplasty (THA) for suspected periprosthetic joint infections (PJIs) is limited. This study aimed to analyse (1) the value of US-determined fluid film, (2) characterisation of the pre- and intraoperative microbiological spectrum and resistance patterns and (3) the concordance between preoperative synovial fluid and intraoperative culture results. Methods. We analysed 366 US-examinations from 340 patients prior to revision THA. Selected cases were categorized into clearly infected, non-infected and inconclusive, according to the International Consensus Meeting (ICM) 2018 Criteria. If US-determined fluid film was <1mm, no aspiration was performed based on our institutional standard protocol. Patients were grouped into no-aspiration (144/366;[39.3%]), dry-tap (21/366;[5.7%]) and a successful-tap (201/366;[54.9%]). The microbiological spectrum and antibiotic resistance patterns were determined and differences were compared between pre- and intraoperative results. Results. The absence of US-determined fluid film showed no correlation with the presence of hip PJI. Overall, 29.9% cases of the no-aspiration-group had a confirmed PJI. Discrepancies were found in 43.2% between successful taps and intraoperative cultures. The most prevalent microorganisms in preoperative synovial fluid were Staphylococcus epidermidis (20.9%), Staphylococcus aureus (20.9%) and Enterococcus faecalis (9.3%). The most prevalent microorganisms in intraoperative cultures were Staphylococcus epidermidis, Cutibacterium acnes and other coagulase-negative Staphylococci (14.2%). Additional microorganisms were identified in 43.8% intraoperatively. Staphylococcus aureus was more often detected preoperatively (20.9% vs. 5.8%;P=0.003), and Cutibacterium acnes intraoperatively (2.3% vs. 14.4%;P=0.01). There were no differences between the antibiotic resistance patterns of pre- and intraoperative concordant microorganisms. Conclusion. Absence of US-determined fluid film cannot rule out the presence of hip PJI. US-guided joint aspirations is a well-established technique. However, the preoperative analysis of synovial fluid shows high discrepancies especially in Cutibacterium acnes and other rare gram-positive microorganisms compared to intraoperative cultures

Aim. Culture-based conventional methods are still the gold standard to identify microorganisms in hip and knee PJIs diagnosis. However, such approach presents some limitations due to prior antimicrobial treatment or the presence of unusual and fastidious organisms. Molecular techniques, in particular specific real-time and broad-range polymerase chain reaction (PCR), are available for diagnostic use in a suspected PJI. However, limited data is available on their sensitivity and specificity. This study aimed to evaluate the performance of a rapid and simple Investigational Use Only (IUO) version of the BioFire® JI multiplex PCR panel when compared to traditional microbiological procedures. Method. Fifty-eight native synovial fluid samples were recovered from 49 patients (female n=26; male =23) who underwent one or multiple septic or aseptic revision arthroplasties of the hip (n=12) and knee (n=46). The JI panel methodology was used either on specimens freshly collected (n=6) or stored at −80°C in our Musculoskeletal Biobank (n=52). The JI panel performance was evaluated by comparison with culture reference methods. Patient's medical records were retrieved from our institutional arthroplasty registry as well as our prospectively maintained PJI infection database. Results. The JI panel identified additional microorganisms in 3/39 (7.7%) positive cases, and a different microorganism in 1/39 (2.6%) sample. Out of 9/58 (15.5%) culture negative samples, two (22%) were positively detected by the JI panel. In total 49/58 (84%) native synovial fluid specimens were positive by culture methods, versus 39/58 (81.2%) with the JI panel. Ten samples are currently under investigation for confirmatory results. Out of 39 positive detections with the JI panel, 35 (89.7%) were concordant with the identified microorganism (n=29 same species; n=6 same genus). The combined information from the JI panel results and clinical records revealed the existence of 6/58 (10.3%) PJIs’ cases which would have required a different antibiotic therapeutic approach. Conclusions. The work presented, provides additional value for the clinical use of the JI panel to the improvement of PJI management in terms of rapid and successful treatment decisions, patient outcome, and healthcare costs. This technique shows high sensitivity to detect PJIs specific microorganisms in both fresh as well frozen native synovial fluid samples, thus emphasizing its use for retrospective studies analysis

Aim. In severe cases of postoperative spinal implant infections (PSII) multiple revision surgeries may be needed. Little is known if changes of the microbiological spectrum and antibiotic resistance pattern occur between revision surgeries. Therefore, the aim of this study was to analyze the microbiological spectrum and antibiotic resistance pattern in patients with multiple revision surgeries for the treatment of PSII. Furthermore, changes of the microbiological spectrum, distribution of mono vs. polymicrobial infections, and changes of the antimicrobial resistance profile in persistent microorganisms were evaluated. Method. A retrospective analysis of a prospectively maintained single center spine infection database was performed with a minimum follow-up of 3 years. Between 01/2011 and 12/2018, 103 patients underwent 248 revision surgeries for the treatment of PSII. Overall, 20 patients (6 male/14 female) underwent 82 revisions for PSII (median 3; range 2–12). There were 55/82 (67.1%) procedures with a positive microbiological result. Microbiological analysis was performed on tissue and implant sonication fluid. Changes in microbial spectrum and antibiotic resistance pattern between surgeries were evaluated using Chi-Square and Fisher's exact test. Results. In total, 74 microorganisms (83.3% gram-positive; 10.8% gram-negative) were identified. The most common microorganisms were Staphylococcus epidermidis (18.9%) and Cutibacterium acnes (18.9%). All S. epidermidis identified were methicillin-resistant (MRSE). Overall, there were 15/55 (27.3%) polymicrobial infections. The microbiological spectrum changed in 57.1% (20/35) between the revision stages over the entire PSII period. In 42.9% (15/35) the microorganism persisted between the revision surgeries stages. Overall, changes of the antibiotic resistance pattern were seen in 17.4% (8/46) of the detected microorganisms comparing index revision and all subsequent re-revisions. Moreover, higher resistance rates were found for moxifloxacin and for ciprofloxacin at first re-revision surgery compared with index PSII revision. Resistances against vancomycin increased from 4.5% (1/23) at index PSII revision to 7.7% (2/26) at first re-revision surgery. Conclusions. Changes of the microbiological spectrum and the resistance pattern can occur in patients with severe PSII who require multiple revision surgeries. It is important to consider these findings in the antimicrobial treatment of PSII. The microbiological analysis of intraoperative tissue samples should be performed at every revision procedure for PSI

Purpose. Unexpected-positive-intraoperative-cultures (UPIC) in presumed aseptic revision-total-knee-arthroplasties (rTKA) are common, and the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, an identification of an underlying pathogen was not possible, so called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate alpha defensin (AD) levels in these patient populations. Methods. In this retrospective analysis of our prospectively maintained biobank, we evaluated synovial AD levels from 143 rTKAs. The 2018-Musculoskeletal Infection Society score (MSIS) was used to define our study groups. Overall, 20 rTKA with UPIC with a minimum of one positive intraoperative culture with MSIS 2-≥6 and 14 UNIC samples with MSIS≥6 were compared to 34 septic culture-positive samples (MSIS ≥6) and 75 aseptic culture-negative (MSIS 0–1) rTKAs. Moreover, we compared the performance of both AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) to test the presence of AD in native and centrifuged synovial fluid. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were considered. Results. AD was detected in 31/34 (91.2%) samples from the infected-group and in 14/14 (100%) samples in the UNIC group. All UPIC samples showed a negative AD result. Positive AD samples were highly (p<0.001) associated with culture positive and infection related histopathological results. Moreover, we found significantly (p=0.001) more high-virulent microorganisms 19/34 (55.9%) in the infected-group compared to the UPIC-group (0/20). Samples from the infected group with high virulent microorganisms 17/19 (89.5%) showed a positive AD. The presence of methicillin resistant Staphylococcus epidermis (MRSE) led to increased AD (p=0.003) levels when compared to those determined in samples positive for methicillin susceptible S. epidermdis (MSSE). ELISA and ADLF tests were positive with centrifuged (8/8) and native (8/8) synovial fluid. Conclusion. AD showed a solid diagnostic performance in infected and non-infected revisions, and it provided an additional value in the diagnostic of UPIC and UNIC associated to rTKAs. AD levels produced by patients with PJIs caused by high-virulent microorganisms and MRSE are significantly higher compared to those in patients with PJIs caused by either low-virulent or antibiotic susceptible microorganisms. Centrifugation of synovial fluid had no influence in the outcome of ADLF quantification. Keywords: Alpha-defensin, UPIC, UNIC, revision-knee-arthroplasty

Aim. Bone and joint infections (BJIs) are serious infections requiring early optimized antimicrobial therapy. BJIs can be polymicrobial or caused by fastidious bacteria, and the patient may have received antibiotics prior to sampling, which may decrease the sensitivity of culture-based diagnosis. Furthermore, culture-based diagnosis can take up to 14 days. Molecular approaches can be useful to overcome these concerns. The BioFire® system performs syndromic multiplex PCR in 1 hour, with only a few minutes of sample preparation. The BioFire® Joint Infection (JI) panel (BF-JI), recently FDA-cleared, detects both Gram-positive (n=15) and Gram-negative bacteria (n=14), Candida, and eight antibiotic resistance genes directly from synovial fluids. The aim of this study was to evaluate its performance in acute JIs in real-life conditions. Method. BF-JI was performed on synovial fluid from patients with clinical suspicion of acute JI, either septic arthritis or periprosthetic JI, in 6 French centers. The results of BF-JI were compared with the results of culture of synovial fluid and other concomitantly collected osteoarticular samples obtained in routine testing in the clinical microbiology laboratory. Results. From July 2021 to May 2022, 319 patients (including 10 children < 5y and 136 periprosthetic infections) had been included in the study. The BF-JI test was invalid for one patient (not retested). Among the 318 remaining patients, overall concordance with comparative microbiology methods was 88% (280/318): 131 samples were negative with both BF-JI and culture, and 149 samples were positive with the same microorganisms using complementary techniques. In 33 cases (10.4%), BF-JI was negative while culture was positive: 18 microorganisms were not targeted by BF-JI (including Staphylococcus epidermidis, n=10, and Cutibacterium acnes, n=2); 15 microorganisms targeted by BF-JI were obtained in culture but not by the molecular test (false-negative 4.7%). In 20 cases, BF-JI was positive while culture was not: 12 patients had received antibiotics before sampling, and 7 cases involved fragile and fastidious bacteria (Kingella kingae, n=5; Neisseria gonorrhoeae, n=2). In 6 cases, both BF-JI and culture were positive, but no yielding the same bacteria (polymicrobial specimens). Conclusions. In acute JIs, the BF-JI panel shows a good concordance with culture for the microorganisms targeted by the panel. Therefore, this molecular tool may have a place in microbiological diagnosis of acute JIs in order to confirm JI faster than culture. Moreover, it allows easy detection of difficult-to-culture bacteria. Acknowledgements. study was supported by bioMérieux, who provided all reagents

Aim. Treatment recommendations for periprosthetic joint infections (PJI) include surgical debridement, antibiotic therapy or staged revision. In surgical related foot and ankle infections (SR-FAI), implant removal will lead to instability. Debridement is difficult because the implant is outside the joint. Recommendations regarding PJI treatment can therefore not be extrapolated to the treatment of SR-FAI. Method. We searched PubMed for the etiology and treatment of SR-FAI, taken into account the time of occurrence, causative microorganisms and surgical treatment options. We integrated this knowledge into a treatment algorithm for SR-FAI. Results. Within the first 6 weeks after surgery, it is difficult to distinguish acute osteomyelitis from surgical site infection in which infection is limited to the soft tissue. The predominantly causative microorganism is Staphylococcus aureus. No debridement can be performed, because of the diffuse soft tissue inflammation and the absence of a joint space. If early SR- FAI is suspected without signs of systemic symptoms, fistula or abscess, empirical antibiotic treatment covering Staphylococcus aureus is recommended. If there is suspicion of ongoing SR-FAI after 2 weeks of empirical treatment, samples for culture after an antibiotic free window should be obtained to identify the causative microorganisms. If SR-FAI is confirmed, but there is no consolidation yet, targeted antibiotic treatment is given for 12 weeks without initial implant removal. In all other cases, debridement and samples for culture should be obtained after an antibiotic free window. Staged revision surgery will be performed if there is still a nonunion. Conclusions. Treatment algorithm regarding PJI cannot be extrapolated to the treatment of SR-FAI. Until now, no treatment guideline for SR-FAI is available. We have introduced a treatment algorithm for the treatment of SR-FAI. The guideline will be validated during the next 2 years

Aims. Achievement of accurate microbiological diagnosis prior to revision is key to reducing the high rates of persistent infection after revision knee surgery. The effect of change in the microorganism between the first- and second-stage revision of total knee arthroplasty for periprosthetic joint infection (PJI) on the success of management is not clear. Methods. A two-centre retrospective cohort study was conducted to review the outcome of patients who have undergone two-stage revision for treatment of knee arthroplasty PJI, focusing specifically on isolated micro-organisms at both the first- and second-stage procedure. Patient demographics, medical, and orthopaedic history data, including postoperative outcomes and subsequent treatment, were obtained from the electronic records and medical notes. Results. The study cohort consisted of 84 patients, of whom 59.5% (n = 50) had successful eradication of their infection at a mean follow-up of 4.7 years. For the 34 patients who had recurrence of infection, 58.8% (n = 20) had a change in isolated organism, compared to 18% (n = 9) in the infection eradication group (p < 0.001). When adjusting for confound, there was no association when the growth on the second stage was the same as the first (odd ratio (OR) 2.50, 95% confidence interval (CI) 0.49 to 12.50; p = 0.269); however, when a different organism was identified at the second stage, this was independently associated with failure of treatment (OR 8.40, 95% CI 2.91 to 24.39; p < 0.001). There were no other significant differences between the two cohorts with regard to patient demographics or type of organisms isolated. Conclusion. Change in the identified microorganism between first- and second-stage revision for PJI was associated with failure of management. Identification of this change in the microorganism prior to commencement of the second stage may help target antibiotic management and could improve the success of surgery in these patients. Cite this article: Bone Jt Open 2023;4(9):720–727

Aims. The aim of this study was to assess the incidence the microbiological spectrum and clinical outcome of hip and knee revision arthroplasties with unexpected-positive-intraoperative-cultures (UPIC) at a single center with minimum follow up of 2 years. Methods. We retrospectively analyzed our prospectively maintained institutional arthroplasty registry. Between 2011 and 2020 we performed presumably aseptic rTHA (n=939) and rTKA (n= 1,058). Clinical outcome, re-revision rates and causes as well as the microbiological spectrum were evaluated. Results. In total, 219/939 (23.3%) rTHA and 114/ 1,058 (10.8%) rTKA had a UPIC (p<0.001). Single positive intraoperative cultures were found in 173/219 (78.9%) in rTHA and 99/114 (86.8%) in rTKA, whereas 46/219 (21.0%) rTHA and 15/114 (13.2%) rTKA had positive results in ≥2 intraoperative cultures. A total of 390 microorganisms were found among the 333 cases. Staphylococcus epidermidis 30.9%, CoNS (21.9%), Cutibacterium acnes 21.1%, and Bacillus spp. 7.3% were the most common microorganisms. Overall, detected microorganisms showed high sensitivity to daptomycin (96.6%), vancomycin (97.3%) and linezolid (98.0%). After a minimum follow up of 2 years (rTHA 1,470 (735; 3,738) days; rTKA 1,474 (749; 4,055) days). During the 2-year follow-up, 8 patients died and 5 were lost to follow-up. There were 54/219 (24.7%) re-revision in rTHa and 20/114 (17.5%) in rTKA. Overall, there were 23 (10.5%) septic re-rTHA and 9 (7.9%) septic re-rTKA as well as 31 (14.2%) aseptic re-rTHA and 11 (9.6%) aseptic re-rTKA. Patients with previous septic revisions bevor UPIC procedure showed a significant higher risk for septic re-revision (p<0.05). Moreover, there were less septic re-revisions after single culture positive UPIC (rTHA: 16/173 (9.2%); rTKA 6/99 (6.1%)) compared to ≥2 positive intraoperative cultures UPIC (rTHA: 7/46 (15.2%); rTKA 3/15 (20.0%)). The most common reason for re-revision in the rTHA-group was aseptic loosening of the cup (34.2%) or of the stem (23.3%), dislocation (18.3%) and periprosthetic-fractures (7.8%). In the rTKA-group it was aseptic loosening (40.4%), instability (24.6%) and secondary patella resurfacing (7.9%). There was a higher septic re-revision rate in consecutive revisions than in planned revisions 17.3% vs. 8.5% in the rTHA-group and 14.3% vs. 7.5% in the rTKA-group, p<0.001. Conclusion. UPICs are common in rTJA. The rate was higher in hips which may partly explained by the easier pre op joint aspiration in the knee. UPIC may lead to an increase in subsequent re-revisions

Aims. Microbiological culture is a key element in the diagnosis of periprosthetic joint infection (PJI). However, cultures of periprosthetic tissue do not have optimal sensitivity. One of the main reasons for this is that microorganisms are not released from the tissues, either due to biofilm formation or intracellular persistence. This study aimed to optimize tissue pretreatment methods in order to improve detection of microorganisms. Methods. From December 2017 to September 2019, patients undergoing revision arthroplasty in a single centre due to PJI and aseptic failure (AF) were included, with demographic data and laboratory test results recorded prospectively. Periprosthetic tissue samples were collected intraoperatively and assigned to tissue-mechanical homogenization (T-MH), tissue-manual milling (T-MM), tissue-dithiothreitol (T-DTT) treatment, tissue-sonication (T-S), and tissue-direct culture (T-D). The yield of the microbial cultures was then analyzed. Results. A total of 46 patients were enrolled, including 28 patients in the PJI group and 18 patients in the AF group. In the PJI group, 23 cases had positive culture results via T-MH, 22 cases via T-DTT, 20 cases via T-S, 15 cases via T-MM, and 13 cases via T-D. Three cases under ongoing antibiotic treatment remained culture-negative. Five tissue samples provided the optimal yield. Any ongoing antibiotic treatment had a relevant influence on culture sensitivity, except for T-DTT. Conclusion. T-MH had the highest sensitivity. Combining T-MH with T-DTT, which requires no special equipment, may effectively improve bacterial detection in PJI. A total of five periprosthetic tissue biopsies should be sampled in revision arthroplasty for optimal detection of PJI. Cite this article: Bone Joint Res 2021;10(2):96–104

Aim. The purpose of this study is to analyze the demographic and microbiological variables of acute ankle infections posterior to ankle osteosynthesis and to determine the different characteristics of patients withE. cloacae infection. Method. A multicenter retrospective observational study (4 national hospitals) of acute post osteosynthesis infections of ankle fracture operated between 2015 and 2018 was implemented. The demographic and microbiological variables relating to the surgical intervention and the antibiotic treatment performed were collected. A descriptive assessment of all the variables and a univariate comparison between patients with E. cloacae infection and patients with alternative microorganism infections were performed. The SPSS v25 program for Windows was the choice for statistical analysis. Results. 71 Patients with an average age of 57 years were included, the majority being males (55%). 31% of patients were diabetic, 27% had vascular pathology, and 18.3% had a BMI greater than 35. Trimalleolar fracture was the most common in our study being 52%. 26.8% were open fractures. The microorganisms isolated were: 25% S. aureus, 22.5% E. cloacae and 22.5% polymicrobial. Accounting for polymicrobial infections, the presence of E. cloacae rises to 32%. In the univariate analysis, only significant differences were found in age (patients with E. cloacae infection were older) and the use of VAC therapy. Conclusions. In our series, higher percentages of E. cloacae infection were observed than those described in the literature. There are statistically significant differences in the variables of age and need for VAC therapy. The high incidence of E. cloacae infections suggests the vital importance of adapting antibiotic prophylaxis, ensuring the coverage of this microorganism

Aim. Our aim was to evaluate the prevalence and impact of unexpected intraoperative cultures on the outcome of total presumed aseptic knee and hip revision surgery. Method. Data regarding patients prospectively recruited in our center, who had undergone elective complete hip and knee revision surgery from January 2003 to July 2017 with a preoperative diagnosis of aseptic loosening was retrospectively reviewed. Partial revisions and patients with follow up below 60 months were excluded from the study. The protocol of revision included at least 3 intraoperative cultures. Failure was defined as the need for re-revision due to any-cause at 5 years and/or the need for antibiotic suppressive therapy. Results. A total of 608 cases were initially included in the study, 53 patients were excluded. 123 hip and 432 knee revision surgeries were included. 420 cases (75.7%) had all cultures negative, 114 (20.5%) a single positive culture or two of different microorganisms and 21 (3.8%) had at least 2 positive cultures for the same microorganism. Early failure was found in 4.8% (1/21) of the patients with missed low grade infection. The presence of positive cultures during total exchange was not associated with a higher failure rate than in those with negative cultures (44 of 420, 10.5%). In contrast, patients revised before 24 months had a significant higher rate of re-revision, 18% (15/83) vs. 8.4%. Conclusions. Total hip and knee revisions with unexpected positive cultures were not significantly associated with a higher re-revision risk at 5 years of follow-up. Representing an overall good prognosis. However, revision surgeries performed within the first 24 months have a higher rate of failure

Aim. Prompt recognition and identification of the causative microorganism in acute septic arthritis of native and prosthetic joints is vital to increase the chances of successful treatment. The aim of this study was to independently assess the diagnostic accuracy of the multiplex BIOFIRE® Joint Infection (JI) Panel (investigational use only) in synovial fluid for rapid diagnosis. Method. Synovial fluid samples were prospectively collected at the University Medical Center Groningen from patients who had a clinical suspicion of a native septic arthritis, early acute (post-operative, within 3 months after arthroplasty) periprosthetic joint infection (PJI) or late acute (hematogenous) PJI. JI Panel results were compared to culture-based methods as reference standard. Results. A total of 45 samples were analyzed. The BIOFIRE JI Panel showed a high specificity (100%, 95% CI 73 – 100) and positive predictive value (100%, 95% CI 79 – 100) in all patient categories. Sensitivity and negative predictive value were 83% (95% CI 36 – 99) and 88% (95% CI 47 – 99) respectively for patients with a clinical suspicion of native septic arthritis (n=12), 77% (95% CI: 46 – 94) and 63% (95% CI: 26 – 90) for patients with a clinical suspicion of a late acute PJI (n=14), and 27% (95% CI 7 – 61) and 27% (95% CI: 7 – 61) for patients with a clinical suspicion of an early acute PJI (n=19). Conclusions. The results of this pilot study indicate a clear clinical benefit of the BIOFIRE JI Panel in patients with a suspected native septic arthritis and late acute (hematogenous) PJI, but a low clinical benefit in patients with an early acute (post-operative) PJI due to the absence of low-grade microorganisms in the panel

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. Analysis of microbiological spectrum and resistance patterns as well as the clinical outcome of patients who underwent a Debridement, antibiotics and implant retention (DAIR) procedure in the early phase following failed two-stage exchange arthroplasty of the knee and hip. Method. Of 312 patients treated with two-stage exchange arthroplasty between January 2011 and December 2019, 16 (5.1%) patients (9 knee, 7 hip) underwent a DAIR procedure within 6 months following second stage. We retrospectively analyzed the microbiological results as well as changes in the microbiological spectrum and antibiotic resistance patterns between stages of two-stage exchange arthroplasties and DAIR procedures. Patient's re-revision rates after a minimum follow-up of 12 months following DAIR procedure were evaluated. Moreover, differences between knee and hip and between infected primary total joint replacement (TJRs) and infected revision TJRs as well as patient's host factors and microbiological results regarding the outcome of DAIR were analyzed. Results. In 7/16 (43.8%) patients the first and second stage procedure was culture positive, in 5/16 (31.2%) patients the first and second stage procedure was culture negative and in 4/16 (25%) patients the first stage procedure was culture positive, and the second stage procedure was culture negative. Moreover, 6 (37.5%) out of 16 DAIR procedures showed a positive microbiological result. In 5/7 (71.4%) patients with culture positive second stage procedure a different microorganism compared to first stage procedure was detected. In 6/6 (100%) patients with culture positive DAIR procedure, the isolated microorganisms were not detected during first or second stage procedure. An additional re-revision surgery was necessary in 4/16 (25%) patients after a median time of 31 months (range, 12 to 138 months) at a mean follow up of 63.1 ± 32 months following DAIR procedure. Highest re-revision rates were found in patients with culture positive second stage procedures (3/7 [42.9%]) and patients with culture positive DAIR procedures (2/6 [33.3%]). Conclusions. DAIR procedure seems to be a useful early treatment option following failed two-stage exchange arthroplasty. The re-revision rates were independent of different combinations of culture positive and culture negative first and second stage procedures. The high number of changes in the microbiological spectrum needs to be considered in the treatment of PJI

Aim. Acute post-surgical infection is one of the most serious complications after instrumented thoracolumbar fusion with an incidence of 0.7%-12%. Acute infection can lead to an increase in morbidity, mortality, and economic costs for the healthcare system. The main objective of our study was to determine the variables associated with a higher risk of acute infection after thoracolumbar instrumentation in our center. Methods. We conducted an observational case-control study including instrumented fusions of the thoracolumbar spine performed between 2015 and 2021 at our institution. We included patients with thoracolumbar fusions after a fracture or for the treatment of degenerative pathology. We analyzed demographic variables related to the surgical procedure, the causative microorganism of infection, the outcome of infection treatment, and complications. We performed a descriptive analysis of all variables and a univariate comparison of cases and controls. The dichotomous variables were compared using the Fisher test, while the quantitative variables were compared using the Student's T-test. A p-value of <0.05 is taken into account to consider the statistical significance. SPSS v25 Windows program was used for statistical analyses. Results. 455 patients were included, 53% were male with a mean age of 60 years. 35% of patients had a BMI (Body Mass Index) >30, 21.1% were classified as ASA (American Society of Anesthesiologists) >3, 15.8% were diabetic, and 2.6% were under chronic corticosteroid treatment. In 34.1% of the fusions, the procedure lasted more than 3 hours. We identified 26 post-surgical acute infections (5.7%). Patients with an infection had a higher prevalence of diabetes (14.7% vs 34.6% p=0.012), chronic corticosteroid treatment (2.1% vs 11.5% p=0.026), and a higher percentage of surgeries with duration > 3 hours (32.4% vs. 61.1%, p=0.019). A trend towards significance was also observed in patients classified as ASA >3 (20.3% vs. 34.6%, p=0.088), and BMI >30 (33.8% vs. 53.8%, p=0.054). No significant differences were observed in the rest of the variables studied. The most frequent causative microorganism was S.epidermidis (38%), followed by S.aureus (34%) and polymicrobial infections (34%). Conclusions. There is a significant increase in infection in diabetic patients, patients with chronic corticosteroid treatment, and in surgeries lasting > 3 hours

Aim. Failed consolidation (nonunion) after foot and ankle arthrodesis is a major complication, which can lead to additional revision arthrodesis with increased risk of morbidity. Multiple factors can contribute to developing a nonunion, including a low-grade infection. The aim of this study was to investigate the rate of unsuspected low-grade infection in revision arthrodesis for nonunions after foot and ankle arthrodesis. We also analyzed the outcome of unsuspected low-grade infections. Method. We conducted a retrospective study in The Sint Maartenskliniek, The Netherlands. All patients who underwent revision arthrodesis for assumed aseptic nonunion after foot and ankle arthrodesis between January 2020 and July 2021 were included. Patients were excluded if <5 tissue samples were obtained during revision arthrodesis or if they were treated for infection after the index arthrodesis. For the included patients, at least 5 tissue samples for culture were taken during the revision arthrodesis. The causative microorganisms, antibiotic susceptibility and treatment were assessed. An unsuspected infection was defined as ≥2 positive cultures with phenotypical identical microorganisms. Success was defined as union on imaging during clinical follow-up, without signs of persistent infection after finishing the antibiotic treatment. Results. In total 91 revision arthrodesis due to nonunion were performed. The mean duration between index and revision arthrodesis was 571 days. In 14 patients, an unexpected infection was diagnosed. The most frequent causative bacteria identified were Cutibacterium acnes (n=10) and Staphylococcus spps. (n=5). One infection was caused by a Gram-negative bacilli (Acinetobacter spps.). Two infections were polymicrobial. Of the 14 infections, 12 were treated with antibiotics for 12 weeks, 1 for 6 weeks and 1 was not treated. After one-year follow-up, the success rate was 86% and in one patient re-surgery was performed for a non-infectious reason. Conclusions. In 18% of the revisions for nonunion after foot and ankle arthrodesis, an unexpected low- grade infection was the cause of the nonunion. Nonunion occurring after foot and ankle arthrodesis is a severe complication, leading to additional revision arthrodesis. Low-grade infection should be considered as possible explanation of the nonunion, despite the lack of local inflammatory signs. As 18% of the nonunions were unexpectedly caused by low-grade infection, we strongly recommend obtaining at least 5 tissue samples for culture during revision arthrodesis. The outcome of unexpected infection as cause of nonunion is good, when treated with targeted antibiotics for 12 weeks

Aim. The gold standard treatment for late acute hematogenous (LAH) periprosthetic joint infection (PJI) is surgical debridement, antibiotics and implant retention (DAIR). However, this strategy is still controversial in the case of total knee arthroplasty (TKA) as some studies report a higher failure rate. The aim of the present study is to report the functional outcomes and cure rate of LAH PJI following TKA treated by means of DAIR at a long-term follow-up. Method. A consecutive prospective cohort consisting of 2,498 TKA procedures was followed for a minimum of 10 years (implanted between 2005 and 2009). The diagnosis of PJI and classification into LAH was done in accordance with the Zimmerli criteria (NEJM 2004). The primary outcome was the failure rate, defined as death before the end of antibiotic treatment, a further surgical intervention for treatment of infection was needed and life-long antibiotic treatment or chronic infection. The Knee Society Score (KSS) was used to evaluate clinical outcomes. Surgical management, antibiotic treatment, the source of infection (primary focus) and the microorganisms isolated were also assessed. Results. Among the 2,498 TKA procedures, 10 patients were diagnosed with acute hematogenous PJI during the study period (0.4%). All those 10 patients were operated by means of DAIR, which of course included the polyethylene exchange. They were performed by a knee surgeon and/or PJI surgeon. The failure rate was 0% at the 8.5 years (SD, 2.4) follow-up mark. The elapsed time between primary total knee replacement surgery and the DAIR intervention was 4.7 years (SD, 3.6). DAIR was performed at 2.75 days (SD 1.8) of the onset of symptoms. The most common infecting organism was S. aureus (30%) and E. coli (30%). There were 2 infections caused by coagulase-negative staphylococci and 2 culture-negative PJI. All culture-positive PJI microorganisms were susceptible to anti-biofilm antibiotics. The source of infection was identified in only 3 cases. The mean duration of antibiotic treatment was 11.4 weeks (SD 1.9). The postoperative clinical outcomes were excellent, with a mean KSS of 84.1 points (SD, 14.6). Conclusions. Although the literature suggests that TKA DAIR for acute hematogenous periprosthetic joint infection is associated with high rates of failure, the results presented here suggest a high cure rate with good functional outcomes. Some explanations for this disparity in results may be the correct diagnosis of LHA, not misdiagnosing acute chronic PJI, and a thorough debridement by surgeons specialized in PJI

Aims. The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition. Methods. A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree. Results. Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 10. 9. /l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases. Conclusion. The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article: Bone Joint J 2020;102-B(7):904–911

Aims. During revision procedures for aseptic reasons, there remains a suspicion that failure may have been the result of an undetected subclinical infection. However, there is little evidence available in the literature about unexpected positive results in presumed aseptic revision spine surgery. The aims of our study were to estimate the prevalence of unexpected positive culture using sonication and to evaluate clinical characteristics of these patients. Patients and Methods. All patients who underwent a revision surgery after instrumented spinal surgery at our institution between July 2014 and August 2016 with spinal implants submitted for sonication were retrospectively analyzed. Only revisions presumed as aseptic are included in the study. During the study period, 204 spinal revisions were performed for diagnoses other than infection. In 38 cases, sonication cultures were not obtained, leaving a study cohort of 166 cases. The mean age of the cohort was 61.5 years (. sd. 20.4) and there were 104 female patients. Results. Sonication cultures were positive in 75 cases (45.2%). Hardware failure was the most common indication for revision surgery and revealed a positive sonication culture in 26/75 cases (35%) followed by adjacent segment disease (ASD) in 23/75 cases (30%). Cutibacterium acnes and Staphylococcus epidermidis were the most commonly isolated microorganisms, observed in 45% and 31% of cases, respectively. C. acnes was isolated in 65.2% of cases when the indication for revision surgery was ASD. Conclusion. Infection must always be considered as a possibility in the setting of spinal revision surgery, especially in the case of hardware failure, regardless of the lack of clinical signs. Sonication should be routinely used to isolate microorganisms adherent to implants. Cite this article: Bone Joint J 2019;101-B:621–624

Aim. Bone and Joint Infections (BJIs) present with non-specific symptoms and can be caused by a wide variety of bacteria and fungi, including many anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians currently rely primarily on culture to identify the pathogen(s) responsible for infection. The BioFire. ®. FilmArray. ®. Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) was designed to detect 15 gram-positive (seven anaerobes), 14 gram-negative bacteria (one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel (BBJIP) compared to conventional used as reference methods. Method. In a monocentric study, leftover synovial fluid specimens were collected in a single institution including 4 hospitals and tested using conventional bacterial culture (Standard of Care (SoC)) according to routine procedures following French national recommendations. Specimen has been placed in a refrigerator (4°C) as soon as possible after collection and stored for less than or equal to 7 days before enrollment. Performance of the IUO version of the BBJIP was determined by comparison to SoC for species identification. Results. To date, 201 specimens have been collected and tested using BBJIP. A total of 39 pathogens were obtained in culture. Compared to SoC culture, the overall PPA was 89.7% (35 TP, 4 FN (SA, 1; Strepto Spp, 2; P. micra, 1) and the overall NPA was 99.7% with 16 FP for a total of 5374 bacterial targets screened. Two complementary molecular tests using home-made PCR are underway to definitively conclude about the FN et FP for BBJIP observed in the preset study. Conclusions. The BioFire BJI Panel appears as a promising, sensitive, specific, and robust test for rapid detection of 31 microorganisms (including anaerobes) and eight AMR genes in synovial fluid specimens. The number of pathogens and resistance markers included in the BioFire BJI Panel, together with a reduced time-to-result and increased diagnostic yield compared to culture, is expected to aid in the management of BJIs

Aim. Little is known about microbiological spectrum and resistance patterns as well as the clinical outcome in patients who undergo a repeat first stage procedure as part of a 2-stage revision arthroplasty for the treatment of periprosthetic hip and knee joint infections. Methods. Between 2011 and 2019, a total of 327 2-stage revision arthroplasties were performed on 312 patients with PJI of the knee and hip at our institution. We performed a retrospective analysis of all patients, who underwent a repeat first stage procedure regarding re-revision rate, host factors, culture negative and positive stages, monomicrobial and polymicrobial infections as well as microbiological spectrum and antimicrobial resistance patterns. Results. Overall, 52/312 (16.7%) patients (27 knee/25 hip) underwent a repeat first stage procedure. There were 35/52 (67.3%) culture positive first, 17/52 (32.7%) culture positive repeat first and 12/52 (23.1%) culture positive second stage procedures. In 13/52 (25%) patients a re-revision surgery was necessary at a median follow-up of 46.8 months (range, 12.2 to 93.3 months). High re-revision rates (10/12 [83.3%]) were found in patients with culture positive second stage and low re-revision rates (3/40 [7.5%]; p<0.01) were found in patients with culture negative second stage. The microbiological spectrum changed in 9/11 (81.8%) patients between culture positive first and repeat first stage, in 3/4 (75%) patients between culture positive repeat first and second stage and in 5/6 (83.3%) between culture positive second stage and subsequent re-revision surgery. Moreover, the antimicrobial resistance pattern changed in 6/9 (66.7%) of persistent microorganisms. Conclusion. Microbiological results during first, repeat first and second stage procedures significantly impacted the re-revision rates and changes in microbiological spectrum and resistance patterns between stages are common. However, if eradication of the microorganism at second stage can be accomplished, low re-revision rates can be achieved, even in patients who require a repeat first stage procedure

Aim. Dalbavancin is a novel second-generation lipoglycopeptide antibiotic with strong activity against many gram-positive bacteria and a prolonged half-life of 6–11 days. This allows a once-a-week intravenous application and therefore an outpatient intravenous therapy. Currently, only little is known about the use of Dalbavancin in Periprosthetic joint infection (PJI). The aim of this retrospective study, was to compare the outcome of hip and knee periprosthetic joint infections (PJI) in patients who received dalbavancin (DAL) with patients which was treated by standard of care antimicrobial agents (SoC). Methods. Between 02/2017 and 02/2020 a total of 89 (42 male/47 female) patients with PJI of the hip 56/89 (62.9%) and knee 33/89 (37.1%) who received at least one dosage of Dalbavancin were included. A 1:1 propensity-score (PS) matching between the DAL-group (n=89) and the SoC-group (n=89) was performed, using defined demographic covariates such as body-mass-index, age, sex, causative pathogens, knee or hip joint and infection after primary or revision surgery, surgical site infections, Charlson-comorbidity index and the types of infection (acute, late acute and chronic). Patient's demographics were analysed by our prospectively maintained institutional arthroplasty registry and PJI database. We analysed the outcome of the included patients evaluate the re-infection and re-revision rate and gave details about surgical management and the type of PJI with a minimum follow-up of one year. Results. Microbiological and clinical successes were achieved in 69 (77.5%) patients of the DAL-group and in 66 (74.2%) patients of the SoC-group. In the DAL-group 13 (14.6%) and in the SoC-group 12 (13.5%) patients had an infection related re-revision. Median follow-up was 706 (369; 1310) days in the DAL-group and 1329 (9; 3,549) days in the SoC-group. Overall, polymicrobial infections were found in 20 procedures (DAL-group: 10; SoC-group: 10) and monomicrobial infections in 154 (DAL-group: 75; SoC-group: 79). Polymicrobial infections were found in 20 patients and monomicrobial infections in 154. The most common microorganisms were Staphylococcus epidermidis n=63 (32.3%), Staphylococcus aureus n=27 (13.8%) and Cutibacterium spp. n=22 (11.3%). There are significantly less Gram-positive microorganisms (p=0.034) after re-revisions in patients with DAL treatment. Conclusions. Dalbavancin has excellent safety and high clinical effectiveness for Gram-positive PJIs

Aim. Diagnosis and isolation of a causative organism is imperative for successful treatment of periprosthetic joint infections (PJI). While there are several diagnostic algorithms using microbiology, serum and synovial markers, the preoperative diagnosis of a low-grade infection remains a challenge, particularly in patients with unsuccessful aspiration. An incisional biopsy may be used in these cases as additional diagnostic tool. In this retrospective study we evaluated microbiological findings, sensitivity, and specificity of open synovial biopsies in cases of inconclusive preoperative diagnostics. Methods. In a retrospective databank analysis (2010–2018), we identified 80 TKAs that underwent an open biopsy because of inconclusive results after applying the CDC Criteria (2010) or the MSIS (2011–2018) for PJI. Infection makers in the serum (C-reactive protein [CRP], leucocytes count and interleukin-6 [IL-6]) and in the synovial aspirate (leucocyte count, percentage of neutrophiles) prior to the biopsy were analyzed. All biopsies were performed by suprapatellar mini-arthrotomy. If a subsequent revision surgery was performed, the isolated organisms in the open biopsy were compared to the results in the revision surgery and sensitivity and specificity were calculated. Serum markers were checked for correlation with a positive result in the open biopsy using Cramer-V and Chi. 2. -Test. Results. A positive result in the open biopsy occurred in 32 cases (40%) while 48 cases (60%) showed no growth of microorganisms. A preoperative elevated serum CRP (≥1mg/dl) showed a significant correlation for a positive biopsy (p=0.04). The odds ratio for a positive biopsy was 2.57 (95% CI 1.02–6.46) with elevated serum CRP. A revision surgery of the TKA with additional tissue sampling was performed in 27 (84%) cases with a positive biopsy and in 32 (67%) cases with a negative biopsy. The intraoperative tissue samples from the revision surgery showed microbial growth in only 52% of cases that were believed to be culture positive from the biopsy results, while positive cultures occurred in 41% of the cases with an initially negative biopsy. Patients with ≥ two cultures of the same microorganism in the biopsy presented a positive result in 73% of their revision surgeries. The open biopsy showed a sensitivity of 48% with a specificity of 62% in our collective if revision surgery was performed. Conclusion. Open biopsy may be considered with inconclusive preoperative serum and synovial fluid diagnostics for PJI, but sensitivity and specificity were rather low in this special collective. Further studies with bigger collectives should be performed to determine potential markers with a higher sensitivity

Osteoporosis (OP) and osteoarthritis (OA) are leading causes of musculoskeletal dysfunction in elderly, with chondrocyte senescence, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability as prominent features. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Not surprisingly, the development of OP and OA correlate with dysregulations of the gut microflora in rodents and humans. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes to regulate joint homeostasis. Modulating the abundance of specific gut bacteria, like Lactobacillus and Bifidobacterium, by probiotics or fecal microbiota transplantation appears to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue and holds potential to slow down OP development. The talk will highlight treatment options with probiotics or metabolites for modulating the progression of OA and OP

Aims. To evaluate the histopathological examination of peri-implant tissue samples as a technique in the diagnosis of postoperative spinal implant infection (PSII). Methods. This was a retrospective analysis. Patients who underwent revision spinal surgery at our institution were recruited for this study. PSII was diagnosed by clinical signs, histopathology, and microbiological examination of intraoperatively collected samples. Histopathology was defined as the gold standard. The sensitivity for histopathology was calculated. A total of 47 patients with PSII and at least one microbiological and histopathological sample were included in the study. Results. PSII occurred in approximately 28% of the study population. Histopathology showed a sensitivity of 51.1% in the diagnosis of PSII. The most commonly found pathogens were Cutibacterium acnes and gram-positive staphylococci. Conclusion. Histopathology has low sensitivity for detecting PSII. In particular, infections caused by low-virulence microorganisms are insufficiently detected by histopathology. Cite this article: Bone Joint J 2020;102-B(7):899–903

Aims. Synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells (%PMN) are elevated at periprosthetic joint infection (PJI). Leucocytes produce different interleukins (IL), including IL-6, so we hypothesized that synovial fluid IL-6 could be a more accurate predictor of PJI than synovial fluid WBC count and %PMN. The main aim of our study was to compare the predictive performance of all three diagnostic tests in the detection of PJI. Methods. Patients undergoing total hip or knee revision surgery were included. In the perioperative assessment phase, synovial fluid WBC count, %PMN, and IL-6 concentration were measured. Patients were labeled as positive or negative according to the predefined cut-off values for IL-6 and WBC count with %PMN. Intraoperative samples for microbiological and histopathological analysis were obtained. PJI was defined as the presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in a minimum of two or more samples out of at least four taken. Results. In total, 49 joints in 48 patients (mean age 68 years (SD 10; 26 females (54%), 25 knees (51%)) were included. Of these 11 joints (22%) were infected. The synovial fluid WBC count and %PMN predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 82%, 97%, 94%, 90%, and 95%, respectively. Synovial fluid IL-6 predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 73%, 95%, 90%, 80%, and 92%, respectively. A comparison of predictive performance indicated a strong agreement between tests. Conclusions. Synovial fluid IL-6 is not superior to synovial fluid WBC count and %PMN in detecting PJI. Level of Evidence: Therapeutic Level II. Cite this article: Bone Jt Open 2020;1-12:737–742

Aim. Debridement, antibiotics and implant retention (DAIR) are considered as an optimal curative treatment option for prosthetic joint infection (PJI) when the biofilm is still immature and radical debridement is achievable. There are two main groups of patients suitable for DAIR. Those with an early acute PJI and patients with acute hematogenous PJI. However, there is also a third group of early PJI resulting from a wound healing problem or leaking hematoma. These may be either high or low grade depending on the microorganisms that infected the artificial joint “per continuitatem”. Methods. We retrospectively analysed 100 successive DAIR procedures on prosthetic hip and knee joints performed between January 2010 and January 2022, from total of 21000 primary arthroplasties implanted within the same time period. We only included PJI in primary total replacements with no previous surgeries on the affected joint. Patients data (demographics, biochemical, microbiological, histopathological results, and outcomes) were collected from hospital bone and joint infection registry. The aim of surgery was radical debridement and the mobile parts exchange. The standardized antibiotic regime based on antibiofilm antibiotics. Results. The mean age of patients was 70 years (60% women, 43 hips, 57 knees) with a mean follow-up of 3 years. 45 cases were early acute or related to wound healing problems, 55 were hematogenous PJI. 25 patients received preoperative antibiotics. 6 of these were culture negative. The mean symptom duration was 7 days. Mean age of the prosthesis was 30 days for early, and 1064 days for the hematogenous group. Conclusions. In our cohort the success rate of DAIR is 94% which indicates that the protocol is highly successful in PJI with short-lasting symptoms and “debridable” joints. Antibiotic protocol violation and duration of symptoms may have a role in failures

Aims. We aimed to describe the epidemiological, biological, and bacteriological characteristics of osteoarticular infections (OAIs) caused by Kingella kingae. Methods. The medical charts of all children presenting with OAIs to our institution over a 13-year period (January 2007 to December 2019) were reviewed. Among these patients, we extracted those which presented an OAI caused by K. kingae and their epidemiological data, biological results, and bacteriological aetiologies were assessed. Results. K. kingae was the main reported microorganism in our paediatric population, being responsible for 48.7% of OAIs confirmed bacteriologically. K. kingae affects primarily children aged between six months and 48 months. The highest prevalence of OAI caused by K. kingae was between seven months and 24 months old. After the patients were 27 months old, its incidence decreased significantly. The incidence though of infection throughout the year showed no significant differences. Three-quarters of patients with an OAI caused by K. kingae were afebrile at hospital admission, 11% had elevated WBCs, and 61.2% had abnormal CRPs, whereas the ESR was increased in 75%, constituting the most significant predictor of an OAI. On MRI, we noted 53% of arthritis affecting mostly the knee and 31% of osteomyelitis located primarily in the foot. Conclusion. K. kingae should be recognized currently as the primary pathogen causing OAI in children younger than 48 months old. Diagnosis of an OAI caused by K. kingae is not always obvious, since this infection may occur with a mild-to-moderate clinical and biological inflammatory response. Extensive use of nucleic acid amplification assays improved the detection of fastidious pathogens and has increased the observed incidence of OAI, especially in children aged between six months and 48 months. We propose the incorporation of polymerase chain reaction assays into modern diagnostic algorithms for OAIs to better identify the bacteriological aetiology of OAIs. Cite this article: Bone Joint J 2021;103-B(3):578–583

Aim. Diagnosing prosthetic joint infections(PJI) is sometimes difficult. Being able to identify the bacteria involved in intraoperative samples is an essential diagnostic criterion. There are however some cases in which the traditional cultures are not capable of providing a definitive diagnosis. In this regard, implant sonication has emerged as a complementary test. The aim of this study was to analyze the results of microbiological studies obtained with and without implants sonication, in order to understand its real contribution to diagnosis. Method. We retrospectively evaluated all cases of infected total hip or knee arthroplasty surgically treated between January 2009 and December 2013. The definition of infection met the criteria set out recently in the international consensus meeting. The number and type of bacteria identified in each patient and the type of microbiological study made were registered. Two different groups were created, with and without sonication, and the results were compared. Results. In a total of 93 patients with PJI, there were only three cases (3.2%) in which we failed to isolate any microorganism. In the 41 cases in which sonication was not used, 54 different microorganisms (an average of 1.32 per patient) were found and no microorganism was found in two cases (4.9%). In the 52 patients in whom sonication was used, we identified 74 different microorganisms (an of average 1.42 per patient) and only one case (1.9%) of negative cultures. In 25 patients (27 microorganisms) there was complete correspondence between the findings of sonication and traditional tissue culture. In 22 cases, 34 different microorganisms were found in tissue samples and sonication offered negative cultures. On the other hand, there were four patients in with 13 microorganisms were identified in sonication with negative tissue cultures. Conclusions. An analysis made in our institution several years ago, showed a percentage of culture negative PJI of almost 20%. Since then, several changes have been introduced in our clinical practice. Of these, sonication, whose value has been amply demonstrated in the literature, is the most demanding in terms of logistics. The authors believe that the implementation and especially the widespread adoption of simple rules for proper sampling is effective for a significant reduction in cases where it is not possible to isolate any microorganism in PJI's. We believe sonication should be seen as an additional diagnostic tool that contributes to increasing sensitivity but should not be considered a substitute for traditional study

Aim. We wonder what the results of two stage procedures were in terms of morbidity (amputation, dead) and infection recurrence. We also seek to identify risk factors for failure and see if the results of a second two stage surgery were not even worse. Material and Methods. We retrospectively reviewed 140 prosthetic joint infection (PJI) treated with a two stage procedure. Patient data has been reviewed to determine which factors would be predictive for failure. Results. From the 140 two stages, 98 patients were infection free at two years. Four died in the following year. 38 patients presented a recurrence within the two years: 2 died and 1 was amputated within one year. Nine were further treated with a second two stage procedure and 26 with debridement and implant retention procedures and antibiotics (DAIR). Six of these last received long terms suppressive antibiotics. In total 27 from the 38 were again diseases free at two years follow up. The dead and amputation rates are 4,3% and 0,8 % respectively. The rate of success after the first two stage was 80% and after a second two stage procedure 78%. The final rate of PJI cured is 89,3%. The only difference observed between success and failure after a first two stage procedure was related to microbiology. Polymicrobial infection was 28.6% of the PJI which will fail and only 14,1% in those whose treatment will succeed (p<0.05). Looking to the patients that underwent a second two stage surgery, recurrence involved monomicrobial pattern with a microorganism that has developed a resistance to quinolones. Conclusion. Mortality and amputation in PJI management should be mentioned to patients as significant potential complications. Infection control within a two stage procedure is not as high as reported, unless the final result is considered after secondary procedures. A second two stage procedure was not related with a worse outcome. Our data confirms the poorer outcome of polymicrobial infection. Recurrence in those patients involves monomicrobial infections with resistant microorganisms. Nevertheless, a second two stage procedure appears acceptable when a DAIR procedure and suppressive antibiotherapy is difficult or impossible due to the microorganism resistance profile

Aim. To describe the risk factors, microbiology and treatment outcome polymicrobial prosthetic joint infections (PJI) compared to monomicrobial PJI. Methods. Between January 2011 and December 2021, a total of 536 patients were diagnosed with PJI at our institution. Clinical records were revised, and 91(16.9%) had an isolation of two or more pathogens. Age, sex, previous conditions, Charlson comorbidity score, previous surgery, PJI diagnosis and surgical and antibiotic treatment, from the index surgery onwards were reviewed and compared between groups. Results. Polymicrobial PJI success rate was 57.1%, compared to 85.3% of the monomicrobial PJI(p=0.0036). There were no statistically significative differences between acute and chronic infections. In terms of related risk factors, revision surgery(p=0.0002), fracture(p=0.002), tobacco(p=0.0031) and Body Mass Index (BMI) between 20–25(p=0.0021) were associated to monomicrobial PJI, whereas overweight(p=0.005) and obesity(p=0.02) were linked to polymicrobial PJI. Regarding pathogens, the most common microorganism isolated in monomicrobial was S.aureus (33.5%), followed by S. epidermidis(20%) and gram negative bacilli (12.2%); while S. epidermidis(56%), gram negative bacilli (41.8%) and E.colli (30.8%) were the most frequent in the polymicrobial PJI. Enterococci(p=0.0008), S. epidermidis(p=0.007), E.colli (p=0.0008), gram negative bacilli (p=0.00003) and atypical bacteria (p=0.00001) statistically significative linked to polymicrobial PJI; while S.aureus (p=0.018) was related to monomicrobial PJI. Conclusion. Polymicrobial PJI showed worse outcome compared to monomicrobial PJI in our cohort. In terms of risk factors, overweight, obesity and some pathogens like gram negative bacilli, atypical bacteria, enterococci, S. epidermidis and E.colli were associated with Polymicrobial PJI

An increasing elderly population means joint replacement surgery numbers are projected to increase, with associated complications such as periprosthetic joint infections (PJI) also rising. PJI are particularly challenging due to antimicrobial resistant biofilm development on implant surfaces and surrounding tissues, with treatment typically involving invasive surgeries and systemic antibiotic delivery. Consequently, functionalisation of implant surfaces to prevent biofilm formation is a major research focus. This study characterises clinically relevant antimicrobials including gentamicin, clindamycin, daptomycin, vancomycin and caspofungin within a silica-based, biodegradable sol-gel coating for prosthetic devices. Antimicrobial activity of the coatings against clinically relevant microorganisms was assessed via disc diffusion assays, broth microdilution culture methods and the MBEC assay used to determine anti-biofilm activity. Human and bovine cells were cultured in presence of antimicrobial sol-gel to determine cytotoxicity using Alamar blue and antibiotic release was measured by LC-MS. Biodegradability in physiological conditions was assayed by FT-IR, ICP-MS and measuring mass change. Effect of degradation products on osteogenesis were studied by culturing mesenchymal stem cells in the presence of media in which sol-gel samples had been immersed. Antimicrobial-loaded coatings showed strong activity against a wide range of clinically relevant bacterial and fungal pathogens with no loss of activity from antibiotic alone. The sol-gel coating demonstrated controlled release of antimicrobials and initial sol-gel coatings showed no loss of viability on MSCs with gentamicin containing coatings. Current work is underway investigating cytotoxicity of sol-gel compositions against MG-63 cells and primary osteoblasts. This research forms part of an extended study into a promising antimicrobial delivery strategy to prevent PJI. The implant coating has potential to advance PJI infection prevention, reducing future burden upon healthcare costs and patient wellbeing

The role that fomites have to play in surgical site infection (SSI) and periprostheitic joint infection (PJI) has been observed and researched in the past. However the role that cellphones play in the transfer of microorganisms from hands to surgical sites and the indiscriminate use of cellphones within the Orthopaedics, could increase the risk of infection. This study aimed to measure the contamination of cellphones of health care workers (HCW's) in a South African tertiary hospital. Secondarily was to investigate the cellphone hygiene behaviour of HCW's. A prospective cross-sectional study was conducted in June 2022. Samples were taken from the the participant's cellphones under an aseptic technique and sent for microbiology. The participants also filled out a questionnaire on cellphone behaviour. The inclusion criteria was orthopaedic HCW's working in the institution; This included nurses and doctors in the orthopaedic theatres and main orthopaedic wards. Sixty-two participants were included; 54 from Orthopaedics and 7 from Anaesthesia. From the samples, 71% grew pathogens while 30,64% grew two or more colonies. This is slightly lower than other studies which showed contamination up to 100%. Micro-organisms cultured included Staphylococcus species; S.Epidermidis, Methycillin sensitive S.aureas; and E.Coli. Cellphone hygiene behaviour was also better than most other studies in terms of frequency of cleaning the devices and hand hygiene around cellphone usage. This which may be a contributing factor to the lower micro-organism contamination. This study should be the first of many as we have identified that there are indeed pathogens on cellphones transferable to patients; causing sepsis. Though cellphones have become vital in patients management in the hospital setting, factors such as improvement in cellphone hygiene through education and frequent cleaning of cellphones will aid in disabling the negative impact of cellphones in the orthopaedic environment

Abstract. Background. Prosthetic joint infection (PJI) is a significant cause of morbidity and mortality following knee replacement surgery. Identifying the causative agent(s) and their antibiotic sensitivities is critical in determining the choice of treatment methods used and the likelihood of successful eradication. This study aimed to investigate:. Whether biopsy alone was superior to aspiration alone in specificity and sensitivity for diagnosing PJI following knee replacement. Whether biopsy identifies the same microbiological flora as aspiration. Methods. We identified consecutive patients passing through our knee infection Multi-Disciplinary Team meeting between December 2014 and March 2020. Data was collated data retrospectively using electronic records. Statistical analysis was performed using Stata (Timberlake, February 2020). Results. 65 of 100 patients identified had both pre-operative aspiration and biopsy. In 29% of positive patients, biopsy identified new or additional organisms not previously identified by aspiration. Aspiration had a sensitivity of 70%, specificity of 88%, positive predictive value of 90.3% and negative predictive value of 64.7%. Biopsy had a sensitivity of 97.5%, specificity of 88%, positive predictive value of 92.9% and negative predictive value of 95.7%. Conclusion. Biopsy is superior to aspiration in the diagnosis of PJI and can be performed safely and successfully. It identifies organisms when aspiration may be negative and identifies additional microorganisms in a polymicrobial setting not identified by aspiration alone (29% of positive cases). We would recommend, where possible, aspiration and biopsy as routine pre-operative sampling in order to identify all causative agents and their susceptibilities prior to embarking on revision surgery

Osteomyelitis is an inflammatory condition accompanied by the destruction of bone and caused by an infecting microorganism. Open contaminated fractures can lead to the development of osteomyelitis of the fractured bone in 3-25% of cases, depending on fracture type, degree of soft-tissue injury, degree of microbial contamination, and whether systemic and/or local antimicrobial therapies have been administered. Untreated, infection will ultimately lead to non-union, chronic osteomyelitis, or amputation. We report a case series of 10 patients that presented with post-operative infected non-union of the distal femur with or without prior surgery. The cases were performed at Padmashree Dr. D. Y. Patil Hospital, Nerul, Navi Mumbai, India. All the patients’ consents were taken for the study which was carried out in accordance with the Helsinki Declaration. The methodology involved patients undergoing a two-stage procedure in case of no prior implant or a three-stage procedure in case of a previous implant. Firstly, debridement and implant removal were done. The second was a definitive procedure in form of knee arthrodesis with ring fixator and finally followed by limb lengthening surgery. Arthrodesis was planned in view of infection, non-union, severe arthritic, subluxated knee, stiff knee, non-salvage knee joint, and financial constraints. After all the patients demonstrated wound healing in 3 months along with good radiographic osteogenesis at the knee arthrodesis site, limb lengthening surgeries by tibial osteotomy were done to overcome the limb length discrepancy. Distraction was started and followed up for 5 months. All 10 patients showed results with sound knee arthrodesis and good osteogenesis at the osteotomy site followed by achieving the limb length just 1-inch short from the normal side to achieve ground clearance while walking. Our case series is unique and distinctive as it shows that when patients with infected nonunion of distal femur come with the stiff and non-salvage knee with severe arthritic changes and financial constraints, we should consider knee arthrodesis with Ilizarov ring fixator followed by limb lengthening surgery

Orthopedic Device-Related Infections (ODRIs) are a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria. Current treatments, based on antibiotic administration, have proven to be ineffective. Consequently, there is a need for antibiotic-free alternatives. Antimicrobial peptides (AMPs) are a promising solution due to their broad-spectrum of activity, high efficacy at very low concentrations, and low propensity to induce resistance. We aim to develop a new AMP-based chitosan nanogel to be injected during orthopedic device implantation to prevent ODRIs. Chitosan was functionalized with norbornenes (NorChit) through the reaction with carbic anhydride and then, a cysteine-modified AMP, Dhvar5, a peptide with potent antibacterial activity, even against methicillin-resistant Staphylococcus aureus (MRSA), was covalently conjugated to NorChit (NorChit- Dhvar5), through a thiol-norbornene photoclick chemistry (UV= 365 nm). For NorChit-Dhvar5 nanogels production, the NorChit-Dhvar5 solution (0.15% w/v) and Milli-Q water were injected separately into microfluidic system. The nanogels were characterized regarding size, concentration, and shape, using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and Dynamic light scattering (DLS). The nanogels antibacterial properties were assessed in Phosphate Buffer (PBS) for 6 h, against four relevant microorganisms (Pseudomonas aeruginosa, S. aureus and MRSA, and in Muller- Hinton Broth (MHB), 50% (v/v) in PBS, supplemented with human plasma (1% (v/v)), for 6 and 24 h against MRSA. The obtained NorChit-Dhvar5 nanogels, presented a round-shaped and ∼100 nm. NorChit- Dhvar5 nanogels in a concentration of 10. 10. nanogels/mL in PBS were capable of reducing the initial inoculum of P. aeruginosa by 99%, S. aureus by 99%, and MRSA by 90%. These results were corroborated by a 99% MRSA reduction, after 24 h in medium. Furthermore, NorChit-Dhvar5 nanogels do not demonstrate signs of cytotoxicity against MC3T3-E1 cells (a pre-osteoblast cell line) after 14 days, having high potential to prevent antibiotic-resistant infection in the context of ODRIs

Obesity is correlated with the development of osteoporotic diseases. Gut microbiota-derived metabolite trimethylamine-n-oxide (TMAO) accelerates obesity-mediated tissue deterioration. This study was aimed to investigate what role TMAO may play in osteoporosis development during obesity. Mice were fed with high-fat diet (HFD; 60 kcal% fat) or chow diet (CD; 10 kcal% fat) or 0.2% TMAO in drinking water for 6 months. Body adiposis and bone microstructure were investigated using μCT imaging. Gut microbiome and serum metabolome were characterized using 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry. Osteogenic differentiation of bone-marrow mesenchymal cells was quantified using RT-PCR and von Kossa staining. Cellular senescence was evaluated by key senescence markers p16, p21, p53, and senescence association β-galactosidase staining. HFD-fed mice developed hyperglycemia, body adiposis and osteoporosis signs, including low bone mineral density, sparse trabecular microarchitecture, and decreased biomechanical strength. HFD consumption induced gut microbiota dysbiosis, which revealed a high Firmicutes/Bacteroidetes ratio and decreased α-diversity and abundances of beneficial microorganisms Akkermansiaceae, Lactobacillaceae, and Bifidobacteriaceae. Serum metabolome uncovered increased serum L-carnitine and TMAO levels in HFD-fed mice. Of note, transplantation of fecal microbiota from CD-fed mice compromised HFD consumption-induced TMAO overproduction and attenuated loss in bone mass, trabecular microstructure, and bone formation rate. TMAO treatment inhibited trabecular and cortical bone mass and biomechanical characteristics; and repressed osteogenic differentiation capacity of bone-marrow mesenchymal cells. Mechanistically, TMAO accelerated mitochondrial dysfunction and senescence program, interrupted mineralized matrix production in osteoblasts. Gut microbial metabolite TMAO induced osteoblast dysfunction, accelerating the development of obesity-induced skeletal deterioration. This study, for the first time, conveys a productive insight into the catabolic role of gut microflora metabolite TMAO in regulating osteoblast activity and bone tissue integrity during obesity

Aim. The aim of this systematic review was to determine all cultured bacteria, antibiotic strategies, and their outcome from literature describing treatment of FRI patients between 1990 and 2018. Methods. A systematic literature search was performed on treatment and outcome of FRI. All studies in English that described surgical patient series for treatment of FRI were included, using Medline, Embase, Web of Science, Cochrane, and Google Scholar. Publications before 1990 and studies that did not describe FRI patient treatment or did not report original data (e.g., reviews or meta-analyses) were excluded. Study selection and data collection were done by two authors independently. Main collected parameters were preoperative cultures, use of local antibiotics, postoperative antibiotic protocol, cultured microorganisms, and overall outcome of treatment, i.e., eradication of infection and bony union, recurrence, amputations, revisional surgery, and number of complications. Dichotomous data were pooled using Medcalc, and weighted means were calculated for continuous data using Excel. Results. 2,171 studies were identified. Of these, 110 studies were included, describing 119 patient series, in which 4561 patients (4614 fractures) were treated. The population was predominantly male (76%), and the main location of FRI was the tibia (69%). In 78 (71%) studies, 3,234 microorganisms were cultured, of which Methicillin-sensitive Staphylococcus aureus (MSSA) was found in 1,094 (34%) patients, followed by Coagulase-negative Staphylococci (CNS), 431 (13%), Methicillin-resistant Staphylococcus aureus (MRSA), 283 (9%), and Pseudomonas aeruginosa 276 (9%). Polymicrobial infections were present in 11% of patients. Local antibiotics were used in 63 (53%) patient series, with PMMA being the most frequent carrier (73%). Calcium-based cements were used in nine series (14%). Clear postoperative antibiotic protocols were described in only 39 (35%) studies and differed widely. Bony union and infection eradication were achieved in 92% (CI 90–94) of all patients. Recurrence was seen in 9% (CI 8–11), and amputation was required in 3% (CI 3–4) of patients. The effect of local antibiotics on overall outcome of FRI treatment was unclear. Conclusions. This systematic literature review clearly shows that standardized antibiotic treatment protocols for FRI patients are lacking and that internationally accepted guidelines are required. The data also confirm that S. aureus is the most common microorganism encountered in FRI. Due to the large heterogeneity of used local antibiotics and carriers, a reliable comparison was not feasible. Indications for the use of local antibiotics are unclear, and future prospective studies seem necessary

Aim. Patients with late acute periprosthetic joint infections (PJI) and treated with surgical debridement have a high failure rate. Previous studies have shown that rheumatoid arthritis (RA) is an independent risk factor for treatment failure. We conducted a case-control study to identify predictors for failure in late acute PJI treatment in RA patients. We hypothesize that patients with RA have a higher failure rate compared to controls due to the use of immunosuppressive drugs. Method. Data of an international multicenter retrospective observational study was used. Late acute PJI was defined as a sudden onset of symptoms and signs of a PJI, more than 3 months after implantation. Failure of treatment was defined as persistent signs of infection, relapse with the same or reinfection with a different micro-organism, need for prosthesis removal or death. Cases with RA were matched with cases without RA based on the affected joint. A Cox survival analyses, stratified for RA, was used to calculate hazard ratio's (HR) for failure. Subgroup analyses were used to explore other predictors for treatment failure in RA patients. Results. A total of 40 patients with RA and 80 controls without RA were included. Treatment failure occurred in 65% patients with RA compared to 45% for controls (p= .052). 68% of patients with RA used immunosuppressive drugs at time of PJI diagnosis. The use or continuation of immunosuppressive drugs in PJI was not associated with a higher failure rate; neither were the duration of symptoms and causative microorganism. The time between implantation of the prosthetic joint and diagnosis of infection was longer in RA patients: median 110 (IQR 41-171) vs 29 months (IQR 7.5–101.25). Exchange of mobile components was associated with a lower risk of treatment failure (HR 0.489, 95% CI 0.242–0.989, p-value .047). Conclusions. The use of immunosuppressive drugs does not seem to be associated with a higher failure rate in patients with RA. Mobile exchange in RA patients is associated with a lower risk of failure. This might be due to the significantly older age of the prosthesis in RA patients. Future studies are needed to explore these associations and its underlying pathogenesis

Background. Fracture-related infection (FRI) is treated by adequate debridement, lavage, fracture stabilization (if indicated), adequate soft tissue coverage and systemic antimicrobial therapy. Additional administration of local antibiotics (LA), placed directly in the surgical field, is thought to be beneficial for successful eradication of infection. Aims. 1) To evaluate the effect of local antibiotics on outcome in patients with FRI. 2) To evaluate whether bacterial resistance to the implanted local antibiotics influences its efficacy. Methods. A multinational cross-sectional study was performed in patients with FRI, diagnosed according to the FRI consensus definition, between January 2015 and December 2019. Patients who underwent surgical treatment for FRI at all time points after injury were considered for inclusion. Patients were followed-up for at least 12 months. The primary outcome was the recurrence rate of FRI at follow-up. Inverse Probability for Treatment Weighting (IPTW) modeling and multivariable regression analyses were used to assess the relationship between the application of LA and recurrence rate of FRI at 12 months, 24 months and final follow-up. Results. Overall, 433 FRIs in 429 patients were included. A total of 251 (58.0%) cases were treated with LA. Gentamicin was the most frequently used LA (247/251). Recurrence of infection after surgery occurred in 25/251 (10%) patients who received LA and in 34/182 (18.7%) patients who did not. The use of LA reduced the recurrence rate of FRI at 12 months (HR: 0.69; 95% CI [0.24–1.96]) and 24 months (HR: 0.55; 95% CI [0.22–1.35]). Resistance of cultured microorganisms to the LA was not associated with a higher risk of recurrence of FRI (HR: 0.75, 95% CI [0.32–1.74]). Conclusion. The application of LA in treatment of FRI is likely to reduce the risk of recurrence of FRI as the risk reduction was consistent and clinically relevant but it did not reach statistical significance. High local antibiotic concentrations eradicate most pathogens regardless of susceptibility test results