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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 22 - 22
10 Feb 2023
Horn A Cetner C Laubscher M Tootlah H
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Osteoarticular infections (OAI) are a common cause of morbidity in children, and as opposed to adults is usually caused by haematogenous spread. The bacteriology of OAI in children is not well described in the South African context, therefore this study was designed to determine the bacteriology of OAI in our population. All patients that underwent surgery for the treatment of OAI over a 3-year period were identified and those with positive cultures where organisms were identified from tissue, pus, fluid or blood were included. Duplicate cultures from the same patient were excluded if the organism and antibiotic susceptibility profile was the same. Patients were categorised according to age and class of infection (Septic arthritis, acute osteomyelitis, fracture related infection, post-operative sepsis and chronic osteomyelitis) and organisms were stratified according to these categories. We identified 132 organisms from 123 samples collected from 86 patients. Most cultured organisms were from children older than 3-years with acute haematogenous septic arthritis, osteomyelitis, or both. Methicillin sensitive Staphylococcus aureus accounted for 56% (74/132) of organisms cultured. There were no cases of MRSA. The Enterobacterales accounted for 17% (22/132) of organisms cultured, mostly in the fracture related and post-operative infection groups. Of these, 6 each were extended spectrum B-lactamase producers and AmpC producers. There were no carbapenemase producing Enterobacterales. Kingella kingae was not isolated in any patient. Methicillin sensitive S. aureus is the most common infecting organism in paediatric OAI and an anti-staphylococcal penicillin such as cloxacillin or flucloxacillin is the most appropriate empiric treatment for haematogenous OAI in our environment. In fracture related or post-operative infections, Enterobacterales were more frequently cultured, and treatment should be guided by culture and susceptibility results


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 51 - 51
1 Dec 2021
Lang S Frömming A Ehrenschwender M Neumann C Walter N Loibl M Alt V Rupp M
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Aim. Empiric antibiotic therapy for suspected pyogenic spondylodiscitis (SD) should be initiated immediately with severely ill patients and may also be necessary for culture-negative SD. The aim of this study was to infer an appropriate empiric antibiotic regimen by analyzing the antimicrobial susceptibility of isolated pathogens from microbiologically proven pyogenic spondylodiscitis. Method. We performed a retrospective review of adult patients with clinically proven SD treated at our level 1 trauma center between 2013 and 2020. Demographic data, radiologic findings, and treatment modalities were evaluated. The appropriateness of empiric antibiotic regimens was assessed based on the antibiograms of the isolated pathogens. Anamneses were used to distinguish between community-acquired (CA) and healthcare-associated (HA) pathogens, which included cases that had a hospital stay or invasive intervention in the past 6 months. Results. A total of 155 patients (male: N=88; female: N=67; mean age 66.1 ± 12.4 years) with SD were identified. In n= 74 (47.7%) cases, the infections were associated with the healthcare system (HA). N=34 (21.9%) patients suffered from sepsis. The lumbar spine was involved in 47.1% of the cases, the thoracic spine in 37.3%, and the cervical spine in 7.8%. In 7.8% of the cases, SD occurred in multiple spinal segments. N=96 (62.0%) patients were treated surgically. The mean hospital stay was 36.4 ± 36.3 days. Antibiograms of n=45 patients (HA: N=22; CA: N=23) could be retrospectively evaluated: The most frequently identified pathogens were Staphylococcus aureus (46.7%), Coagulase-negative Staphylococci (17.8%), Enterobacteriaceae (15.6%) and Streptococcus species (15.6%). Overall, 82.2% (HA: 68.2%; CA: 95.5%) of the isolated pathogens were sensitive to piperacillin/tazobactam, 77.8% (HA: 81.8%; CA: 72.2%) to vancomycin, 64.4% (HA: 68.2%; CA: 59.1%) to clindamycin, and 55.6% (HA: 36.4%; CA: 72.7%) to ceftriaxone. To a combination of vancomycin plus meropenem 97.8% of pathogens were sensitive (HA: 95.5%; CA: 100.0%), to vancomycin plus ciprofloxacin 91.1% (HA: 86.4%; CA: 95.7%), and to vancomycin plus cefotaxime 93.3% (HA: 90.9%; CA: 95.7%). In 14 cases, empiric antibiosis was adjusted based on the results of the antibiogram. Conclusions. Antibiotic resistance of CA SD pathogens differed significantly from HA SD. The identification of the pathogen and the analysis of its susceptibility guides the antibiotic therapy. Vancomycin in combination with a carbapenem, broad-spectrum cephalosporin, or fluoroquinolone may be appropriate for empiric treatment of HA SD


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 6 - 6
1 Dec 2015
Kostopoulou F Papathanasiou I Anastasopoulou L Aidarinis C Mourmoura E Malizos K Tsezou A
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Toll-like receptors (TLRs) are crucial components of the immune system that recognize microbial infection and trigger anti-microbial host defense responses. Gram positive bacteria are causative factors of bone infections, as they alter the balance of coordinated activities during bone remodeling, stimulating osteoclastogenesis. The aim of the study was to investigate whether genetic variation in TLR2 and TLR4 genes predisposes to bone infections’ susceptibility. One hundred and twenty patients with bone infections (osteomyelitis) and 200 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs), R753Q [A/G] in TLR2 gene and T399I [C/T] in TLR4 gene. DNA was extracted from whole blood and the above SNPs were typed with PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism) method for genotype identification. All patients were infected by Gram-positive bacteria, predominantly Staphylococcus aureus. Statistical analysis was carried out using the chi-square test. We observed a significantly increased frequency in patients carrying the GA genotype of TLR2 R753Q polymorphism compared to controls (p<0.05). We also found that the A allele was more common in patients than in controls. All individuals carrying the A allele were heterozygous for this variant, while homozygous mutant individuals were not detected in the patients and the control group. In contrast, we found that the TLR4 T399I [C/T] SNP was similarly distributed among the two groups (patients and controls). The mechanism through which TLR2 mediates its effect in bone infections is under investigation. A significant difference was observed in the genotype frequency of TLR2 R753Q [A/G] polymorphism in patients, suggesting that genetic variability in TLR2 gene may be associated with susceptibility to osteomyelitis in response to bacterial invasion in the bone


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 96 - 96
1 Dec 2017
Jiang N Wang L Yu B
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Aim. Cyclooxygenase-2 (COX-2) enzyme is one of the major mediators during inflammation reactions, and COX-2 gene polymorphisms of rs20417 and rs689466 have been reported to be associated with several inflammatory diseases. However, potential links between the two polymorphisms and risk of developing post-traumatic osteomyelitis remain unclear. The present study aimed to investigate associations between the rs20417 and rs689466 polymorphisms and susceptibility to post-traumatic osteomyelitis in Chinese population. Methods. A total of 189 patients with definite diagnosis of post-traumatic osteomyelitis and 220 healthy controls were genotyped for rs20417 and rs689466 using the genotyping method*. Chi-square test was used to compare differences of genotype distributions as well as outcomes of five different genetic models between the two groups. Results. Significant association was found between rs689466 and post-traumatic osteomyelitis by recessive model (GG vs. AA + AG) (OR = 1.74, 95% CI: 1.098–2.755, P =0.018). Although no statistical differences were identified of rs689466 between the two groups by allele model (P = .098) or homozygous model (P = 0.084), outcomes revealed a tendency that allele G may be a risk factor and people of GG genotype may be in a higher risk to develop post-traumatic osteomyelitis in Chinese population. However, no significant link was found between rs20417 and susceptibility to post-traumatic osteomyelitis in this Chinese cohort. Conclusions. To our knowledge, we reported for the first time that COX-2 gene polymorphism rs689466 may contribute to the increased susceptibility to post-traumatic osteomyelitis in Chinese population. *SNaPshot®


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XL | Pages 112 - 112
1 Sep 2012
Molina-Manso D del Prado G Manrubia-Cobo M Ortiz-Pérez A Cordero-Ampuero J Gómez-Barrena E
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INTRODUCTION. Prosthetic joint related-infections (PJRI) are severe complications in orthopaedic surgery. Staphylococcus aureus and Staphylococcus epidermidis are the most commonly isolated pathogens from implants (1). The variable antimicrobial susceptibility found in these microorganisms, makes it necessary to perform individual susceptibility studies in order to select the best antibiotic combination for clinical management (2). MATERIAL AND METHODS. 35 staphylococcal strains (17 S. aureus, 18 S. epidermidis) were isolated from PJRI using a previously described sonication protocol (3). Biofilm-producing collection strains S. aureus 15981 (4) and S. epidermidis ATCC 35984 were also included in the study. In vitro susceptibility was evaluated against 7 antimicrobial agents: rifampin, vancomycin, ciprofloxacin, cotrimoxazole, cloxacillin, clindamycin, and daptomycin. Minimal Inhibitory Concentration (MIC) assays were determined according to EUCAST recommendations and breakpoints (5). Minimal Bactericidal Concentration (MBC) was also calculated by colony counting after plating the well contents. RESULTS. Antibiotic susceptibility assay results are shown in tables 1 and 2. It is especially remarkable the high number of meticillin-resistant S. aureus (MRSA) strains. Cotrimoxazole and clindamycin showed better results for S. aureus. Rifampin, vancomycin, and daptomycin showed a very good activity, although some resistant strains were detected for the first two. MBC values showed a strain-dependant activity of rifampin and vancomycin. Only daptomycin showed bactericidal activity against all the tested strains. DISCUSSION & CONCLUSIONS. The treatment of PJRI is still a challenge due to the variable antibiotic susceptibility and the growing number of multidrug-resistant strains. The high number of MRSA detected in our study, makes it necessary to search other antibiotics as an alternative to vancomycin, the traditional elective treatment. The high in vitro activity of daptomycin against the tested strains suggests that it could be an important alternative according to other promising results (6). Rifampin associated with other antimicrobials and cotrimoxazole, with a good in vitro activity against most MRSA strains, could be other potential strategies (7, 8)


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 5 - 5
1 Dec 2017
Jiang N Zhao X Hou Y Yu B
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Aim. Previous studies have indicated that TNF-α and lymphotoxin-α (LTA) gene polymorphisms associate with the development of several different inflammatory diseases. However, potential associations of such gene polymorphisms with the susceptibility to extremity chronic osteomyelitis remain unknown. This study aimed to investigate potential links between TNF-α gene polymorphisms (rs1800629, rs361525, rs1799964, rs1800630, rs1799724 and rs1800750) and LTA gene polymorphism (rs909253) and the risk of developing extremity chronic osteomyelitis in Chinese population. Method. A total of 233 patients with extremity chronic osteomyelitis and 200 healthy controls were genotyped for the above 7 polymorphisms of TNF-α and LTA genes using the genotyping method*. Results. Significant difference was found regarding the genotype distribution of rs909253 between patients and healthy controls (P = 0.002). The mutant allele C frequency of rs909253 in patient group was significantly higher than that in control group (P = 0.001). Significant associations were identified between rs909253 and the risk of developing chronic osteomyelitis by dominant model (P = 0.040), recessive model (P = 0.002) and homozygous model (P = 0.001). Additionally, the mutant allele T frequency in rs1799964 in patient group was significantly higher than that in control group (P = 0.035). Significant link was found between rs1799964 and susceptibility to chronic osteomyelitis by recessive model (P = 0.048). However, no significant outcomes were identified regarding other TNF-α gene polymorphisms between the two groups. Conclusions. The present study demonstrated that rs909253 and rs1799964 polymorphisms may associate with the risk of developing chronic osteomyelitis in Chinese population. *SNaPshot


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 7 - 7
1 Feb 2012
Malik M Bayat A Jury F Oliver W Kay P
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The Osteoprotegerin/RANK/RANKL system has been implicated in the biological cascade of events initiated by particulate wear debris and bacterial infection resulting in periprosthetic bone loss around loosened total hip arthroplasties (THA). Individual responses to such stimuli may be dictated by genetic variation and we have studied the effect of single nucleotide polymorphisms (SNPs) within these genes. We performed a case control study of the Osteoprotegerin, RANK and RANKL genes for possible association with deep sepsis or aseptic loosening. All patients included in the study were Caucasian and had had a cemented Charnley THA and polyethylene acetabular cup. Cases consisted of 91 patients with early aseptic loosening and 71 patients with microbiological evidence at surgery of deep infection. Controls consisted of 150 THAs that were clinically asymptomatic for over 10 years and demonstrated no radiographic features of aseptic loosening. DNA samples from all individuals were genotyped using Taqman allelic discrimination. The A allele (p<0.001) and homozygous genotype A/A (p<0.001) for the OPG-163 SNP were highly associated with aseptic failure. Additionally, the RANK-575 (C/T SNP) T allele (p=0.004) and T/T genotype (p=0.008) frequencies were associated with aseptic failure. No statistically significant relationship was found between aseptic loosening and the OPG- 245 or OPG-1181 SNPs. When the septic group was compared to controls, the frequency of the A allele (p<0.001) and homozygous genotype A/A (p<0.001) for the OPG-163 SNP were statistically significant. No statistically significant relationship was found between septic failure and the OPG- 245, OPG-1181 or RANK-575 SNPs. Aseptic loosening and possibly deep infection of THA may be under genetic influence to candidate susceptibility genes. SNP markers may serve as predictors of implant survival and aid pharmacogenomic prevention of THA failure


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 23 - 23
1 Dec 2019
Poilvache H Ruiz-Sorribas A Rodriguez-Villalobos H Sakoulas G Cornu O van Bambeke F
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Aim

Irrigation is a major step during debridement surgery in the context of Prosthetic Joint Infections (PJI), but its effects on biofilms are poorly described.

The present study aims at evaluating the effect of PW alone or followed by antibiotics on MSSA and MRSA biofilms grown on Ti6Al4V coupons in-vitro.

Method

Strains: 1 reference (MSSA: ATCC25923; MRSA: ATCC33591) and 2 clinical MSSA and MRSA isolated from PJI.

Biofilm culture: Coupons were incubated for 24h at 37°C with bacteria (starting inoculum ∼6.6Log10CFU/mL in TGN [TSB + 1% glucose + 2% NaCl]), under shaking at 50rpm.

Treatment: Half of the coupons were irrigated with 50mL physiological serum from 5cm using a Stryker Interpulse; the coupons were then either analysed (ControlT0 and PWT0) or reincubated for 24h in TGN or TGN containing flucloxacillin (MSSA) or vancomycin (MRSA) at MIC or 20mg/L.

Analysis: Coupons were rinsed twice with PBS. Biomass was measured by crystal violet (CV) assay. CFUs were counted after recovering bacteria from coupons using sonication and TSA plating.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 87 - 87
24 Nov 2023
De Bleeckere A Vandendriessche S Messiaen A Crabbé A Boelens J Coenye T
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Aim. There is growing evidence that bacteria encountered in periprosthetic joint infections (PJI) form surface-attached biofilms on prostheses, as well as biofilm aggregates embedded in synovial fluid and tissues. However, models allowing the investigation of these biofilms and the assessment of their antimicrobial susceptibility in physiologically relevant conditions are currently lacking. To address this, we developed a synthetic synovial fluid (SSF) model and we validated this model in terms of growth, aggregate formation and antimicrobial susceptibility testing, using multiple PJI isolates. Methods. 17 PJI isolates were included, belonging to Staphylococcus aureus, coagulase negative staphylococci, Cutibacterium acnes, Pseudomonas aeruginosa, enterococci, streptococci, Candida species and Enterobacterales. Growth and aggregate formation in SSF, under microaerophilic or anaerobic conditions, were evaluated using light microscopy. The biofilm preventing concentration (BPC) and minimum biofilm inhibitory concentration (MBIC) of relevant antibiotics (doxycyclin, rifampicin and oxacillin) were determined for the staphylococcal strains (n=8). To this end, a high throughput approach was developed, using a fluorescent viability resazurin staining. BPC and MBIC values were compared to the minimum inhibitory concentration (MIC) obtained with conventional methods. Results. The SSF model allowed all isolates to grow well under microaerophilic or anaerobic conditions. When cultured in SSF, all isolates formed biofilm aggregates, varying in size and shape along different species. A susceptibility testing method based on measuring resazurin-derived fluorescence was successfully developed, allowing high throughput determination of the BPC and the MBIC in SSF. For all staphylococci cultured in SSF a reduced susceptibility to the tested antibiotics was observed when compared to susceptibility data obtained in general medium. For rifampicin and doxycyclin the BPC was consistently higher than the MIC (two- to fourfold dilution difference for rifampicin and four- to sixfold dilution difference for doxycyclin). For oxacillin the MIC equaled the BPC for two isolates, while for the other isolates the BPC was higher than the MIC (two- to fourfold dilution difference). Expectedly, the MBIC was higher than the BPC and differences with the MIC were even more pronounced for all antibiotics tested (differences of six- to fourteenfold dilutions were observed). Conclusion. Our data indicate that the in vitro SSF model could provide more insight in how PJI-related pathogens form biofilms in physiologically relevant conditions. The BPC and MBIC were consistently and substantially higher than MIC. This model could be a valuable addition to evaluate the antimicrobial susceptibility in biofilms in a PJI context. Sources of funding: FWO-Vlaanderen (grant G066523N)


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 63 - 63
24 Nov 2023
Prebianchi SB Santos INM Brasil I Charf P Cunha CC Seriacopi LS Durigon TS Rebouças MA Pereira DLC Dell Aquila AM Salles M
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Aim. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is commonly associated with serious cases of community-onset skin and musculoskeletal infections (Co-SMSI). Molecular epidemiology analysis of CA-MRSA recovered from skin and soft tissues specimens is lacking in Latin America. This study aimed to identify phenotypic and genotypic features of MRSA isolates recovered from patients presenting Co-SMSI. Methods. Consecutive MRSA isolates recovered from Co-SMSI of patients admitted from March 2022 to January 2023 in a Brazilian teaching hospital were tested for antimicrobial resistance and characterized by their genotypic features. Identification was carried out by automated method and through MALDI-TOF MS. Antimicrobial susceptibility was tested by disk diffusion, broth microdilution and E-test strips for determination of the minimal inhibitory concentration (MIC) according to recommendations from the Brazilian Committee on Antimicrobial Susceptibility Testing (BrCAST) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Gene mecA characterization and Sccmec typing were performed by multiplex polymerase chain reaction (PCR) assay, and gene lukF detection by single PCR. Patients were prospectively followed up for two months, in order to determine their clinical characteristics and outcomes. Results. Overall, 48 Staphylococcus aureus isolates were obtained from 68 samples recovered from patients with Co-SMSI. Twenty two (42%) were phenotypically characterized as MRSA, although mecA gene was only identified in 20 of those samples. Sccmec was untypable in 12 isolates, Sccmec was type II in 4 isolates and 2 were classified as type IVa. LukF gene was identified in 5 isolates. Antimicrobial resistance profile showed that all isolates were susceptible to linezolid and vancomycin with MIC = 1 and MIC = 2 in 66,7% and 33.3%, respectively. Susceptibility to quinolones was worryingly low and none of the isolates were sensitive to usual doses of ciprofloxacin and levofloxacin, and showed increased rates of resistance to increased exposure to these drugs, as well. Isolates were both susceptible to gentamicin and tetracycline in 85% and resistance to also Sulfamethoxazole/Trimethoprim occurred in only 2 isolates. Mortality rate evaluated within 1 month of the initial evaluation was 10% among MRSA isolates. Conclusions. Our results showed that CA-MRSA isolates causing Co-SMSI demonstrated an alarming pattern of multidrug resistance, including to β-lactam and quinolones, which have been commonly prescribed as empirical therapy for patients with skin, soft tissue and musculoskeletal infections


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 14 - 14
1 Oct 2022
Sliepen J Depypere M Onsea J Debaveye Y Govaert G Ijpma F Zimmerli W Metsemakers W
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Purpose. Fracture-related infection (FRI) is an important complication related to orthopaedic trauma. Although the scientific interest with respect to the diagnosis and treatment of FRI is increasing, data on the microbiological epidemiology remains limited. Therefore, the primary aim of this study was to evaluate the microbiological epidemiology related to FRI, including the association with clinical symptoms and antimicrobial susceptibility data. The secondary aim was to analyze whether there was a relationship between the time to onset of infection and the microbiological etiology of FRI. Methods. Over a five-year period, FRI patients treated at the University Hospitals of Leuven, Belgium, were retrospectively included. The microbiological etiology and antimicrobial susceptibility data were analyzed. Patients were classified as having an early (<2 weeks after implantation), delayed (2–10 weeks) or late-onset (> 10 weeks) FRI. Results. One hundred ninety-one patients with 194 FRIs, mainly involving the tibia (23.7%) and femur (18.6%), were included. Staphylococcus aureus was the most frequently isolated pathogen, regardless of time to onset (n=61; 31.4%), followed by S. epidermidis (n=50; 25.8%) and non-epidermidis coagulase-negative staphylococci (n=35; 18.0%). Polymicrobial infections (n=49; 25.3%), mainly involving Gram-negative bacilli (n=32; 65.3%), were less common than monomicrobial infections (n=138; 71.1%). Virulent pathogens in monomicrobial FRIs were more likely to cause pus or purulent discharge (n=45;54.9%; p=0.002) and fistulas (n=21;25.6%; p=0.030). Susceptibility to piperacillin/tazobactam for GNB was 75.9%. Vancomycin covered 100% of Gram-positive cocci. Conclusion. The high frequency of polymicrobial infections, including Enterobacterales and enterococci, should be considered when choosing an empirical regimen, especially for early FRI. However, since antibiotic stewardship is the cornerstone of good antibiotic practice, overuse and misuse of broad-spectrum empiric therapy should be avoided at all costs. Large multicenter prospective studies are necessary to gain more insight into the added value of (broad) empirical antibiotic therapy


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_3 | Pages 12 - 12
23 Jan 2024
Abdul W Moore IS Robertson A
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Introduction. Perception of ACL injury prevention programs amongst professional netball players and coaches has not been studied. We investigated (1) level of awareness and experience of ACL injury prevention programs; (2) use of ACL injury prevention programs; and (3) barriers to implementing ACL injury prevention program in netball. Methodology. Female netball players representing Welsh senior and under-21 teams and elite and amateur coaches were invited electronically to this web-based study between 1st May–31st July 2021. Information on ACL injury susceptibility and seriousness, knowledge, experience, and implementation of ACL injury prevention programs were ascertained. Results. Twenty-eight players (77.8%) and 29 coaches (13.2%) completed the questionnaire. Seventeen (60.7%) players and 15 (51.7%) coaches reported female athletes were at greater risk for sustaining ACL injuries. Over 90% of respondents identified netball as high-risk, whilst 89% of players and 76% of coaches reported these injuries to be preventable. Two (7.1%) players and 6 (20.7%) coaches utilised ACL injury prevention programs with lack of time and engagement from coaches and players identified. Majority of respondents indicated that their club has neither promoted, advocated nor demonstrated exercises for ACL injury prevention. Over 90% of respondents would utilise such programs if it minimised players risk with appropriate training and information. Conclusion. Study highlights limited knowledge of female athletes’ increased susceptibility of ACL injuries with lack of communication and education of ACL injury prevention programs between sporting associations, coaches and players. Results demonstrate willingness of players and coaches to implement ACL injury prevention programs in Welsh netball


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 33 - 33
1 Oct 2022
Ferry T Kolenda C Briot T Craighero F Conrad A Lustig S Bataillers C Laurent F
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Background. Bacteriophages are natural viruses of interest in the field of PJI. A paper previously reported the PhagoDAIR procedure (use of phages during DAIR) in three patients with PJI for whom explantation was not desirable. As the need to isolate the pathogen before surgery to perform phage susceptibility testing is a strong hindrance for the development of this procedure, we developed post-operative phage injections using ultrasound, in patients infected with S. aureus and/or P. aeruginosa who were eligible for the PhagoDAIR procedure, but for whom phages were not available at the time of surgery. Materials/Methods. We performed a single center, exploratory, prospective cohort study including patients with knee PJI who received phage therapy with ultrasound after performance of a DAIR or a partial prosthesis exchange. All patients had PJI requiring conservative surgery and suppressive antimicrobial therapy (SAT) as salvage procedure. Each case was discussed in multidisciplinary meetings in agreement with French health authority, based on the clinical presentation, and the phage susceptibility testing. The cocktail of highly concentrate active phages (5 mL; about 10. e. 9 PFU/mL) was extemporaneous prepared and administered three times directly into the joint using sonography (1 injection per week during 3 weeks) during the postoperative period, before switching antibiotics to SAT. Results. Seven patients received phages under sonography after the DAIR, and one after a partial exchange (mean age 71 years). All had resection prosthesis or constrained knee prosthesis. Among these seven patients, three were infected with S. aureus (including one MRSA), two were infected with P. aeruginosa (one was a multidrug-resistant isolate), one was infected with both S. aureus and P. aeruginosa and the last one was infected with MRSA, S. epidermidis and Corynebacterium spp.. All patients received a cocktail of active phages provided by Pherecydes Pharma targeting S. aureus or P. aeruginosa. No adverse event was recorded during or after the local injections. All patients were switched to SAT after a primary postoperative antimicrobial therapy of three months. Under SAT, the patient with S. epidermidis co-infection developed a relapse due to the S. epidermidis. With a mean follow-up of 13 months after surgery (from 9 to 24 months), the outcome was favorable for all patients without any sign of infection; none of them had abnormal pain, joint effusion or loosening. Conclusions. Postoperative administration of phages using sonography is a potentially useful procedure in patients with complex PJI for whom a conservative approach is desirable


Aim. Bone and implant-associated infections caused by microorganisms that grow in biofilm are difficult to treat because of persistence and recurrence. Systemic administration of antibiotics is often inefficient because the poor vascularization of the site of infection. This issue has led to the development of biomaterials capable to locally deliver high doses of therapeutic agents to the injured bone with minimal systemic effects. In this context, calcium sulphate/hydroxyapatite (CS/HA) bone graft substitutes are widely used being safe, osteoconductive and resorbable biomaterials that can be easily enriched with consistent amounts of antibiotics. In this in vitro study, the capability of the eluted antibiotics to select the tested bacterial strains for antibiotic resistance was evaluated to confirm the safe use of the product. Method. S. aureus, S. epidermidis and P. aeruginosa isolated in our Institute from bone and joint infection with different resistance phenotypes were used. 6 × 2.5 mm CS/HA discs were generated by pouring the antibiotic loaded formulations in a mold and were used as a modified disk diffusion test. The resistance selection was evaluated by subculturing cells growing on the edge of the zone of inhibition (ZOI) for seven days. Minimum inhibitory concentrations (MICs) of gentamicin and vancomycin were determined by broth microdilution method before and after the selection of resistance assay. In addition, MICs were assessed after seven day passage on antibiotic free agar plates to evaluate if eventual decrease of antibiotic susceptibility was stable or only transient. Results. Commonly, no adaptation in presence of both CS/HA formulations was observed by analysing ZOI on agar medium. The kinetic of decrease of the ZOI was similar between the strains, with the exception of gentamicin resistant staphylococci in presence of gentamicin loaded CS/HA, which was faster with respect to the susceptible strains. Conclusions. The present study shows that elution of gentamicin and vancomycin from CS/HA bone graft substitutes did not induce a decrease in susceptibility to these antibiotics in an in vitro setting, suggesting the safe use of the product


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 25 - 25
1 Dec 2021
Walter N Bärtl S Brunotte M Engelstädter U Ehrenschwender M Hitzenbichler F Alt V Rupp M
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Aim. Fracture-related infection (FRI) is a challenging complication. This study aims to investigate (1) microbial patterns in fracture-related infection (FRI), (2) the comparison of isolated pathogens in FRI patients with early, delayed, and late onset of infection and (3) antibiotic susceptibility profiles to identify effective empiric antibiotic therapy for FRI. Method. Patients treated for FRI from 2013 to 2020 were grouped into early (< 2 weeks), delayed (2– 10 weeks) and late (> 10 weeks) onset of infection. Pathogens detected during treatment were evaluated for pathogens. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations. Results. In total 117 patients (early n=19, delated n=60, late n=38) were included in the study. Infection was polymicrobial in 10 cases (8.6%) and culture-negative in 11 cases (9.4%). Staphylococcus aureus was the most frequently detected pathogen (40.5%), followed by Staphylococcus epidermidis (17.2%) and gram-negative bacteria (16.4%). Pathogen distribution did not differ statistically significant between the groups. Highest effectiveness could be achieved by the combination of meropenem + vancomycin (95.7%) and gentamycin + vancomycin (94.0%). More than 90% of all patients would have also been covered by co-amoxiclav + glycopeptide (93.2%), ciprofloxacin + glycopeptide and piperacillin/tazobactam + glycopeptide (92.3% each) as well as ceftriaxone + glycopeptide (91.5%). Comparing the predicted efficacy of empiric antimicrobial regimens between the subgroups only revealed a statistically significant difference regarding the combination ciprofloxacin with a glycopeptide (F= 3.304, p=.04), for which more patients with an early onset of infection would have been susceptible. Conclusions. Microbiological pattern for the causative microorganism between early, delayed, and late FRI are comparable. Empiric therapy combinations such as meropenem + vancomycin, gentamycin +vancomycin or co-amoxiclav + glycopeptide are effective antibiotic strategies. To bypass unwanted side effects of systemic antibiotics and reduce the risk of antimicrobial resistance, the administration of local antibiotic carriers should be implemented in clinical practice


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 57 - 57
1 Dec 2021
Hotchen A Dudareva M Corrigan R Faggiani M Ferguson J Atkins B Bernard A McNally M
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Aim. To compare pre-referral microbiology and previous bone excision in long bone osteomyelitis with intra-operative microbiology from a specialist centre. Method. A prospective observational cohort study of patients referred to a single tertiary centre who met the following criteria: (i) aged ≥18 years, (ii) received surgery for long bone osteomyelitis and (iii) met diagnostic criteria for long bone osteomyelitis. Patient demographics, referral microbiology and previous surgical history were collected at the time of initial clinic appointment. During surgery, a minimum of 5 intra-operative deep tissue samples were sent for microbiology. Antimicrobial options were classified from the results of susceptibility testing using the BACH classification of long bone osteomyelitis as either Ax (unknown or culture negative), A1 (good options available) or A2 (limited options available). The cultures and susceptibility of pre-referral microbiology were compared to the new intra-operative sampling results. In addition, an association between previous osteomyelitis excision and antimicrobial options were investigated. Results. 79 patients met inclusion criteria during the study period. From these, 39 (49.4%) patients had information available at referral regarding microbiology obtained from either sinus swab (n=16), bone biopsy (n=11), previous osteomyelitis excision sampling (n=7), aspiration (n=4) or blood culture (n=1). From these 39 patients, microbiology information at referral fully matched microbiology samples taken at operation in 8 cases (20.5%). Fifteen of the 39 patients (38.5%) had a different species isolated at surgery compared to referral microbiology. The remaining 16 patients (41.0%) had a culture-negative osteomyelitis on surgical sampling. Based on the microbiology obtained in our centre, 35 patients were classified as A1 (44.3%), 15 as A2 (18.9%) and 29 as culture negative, Ax (36.7%). Patients who had received previous excision of osteomyelitis before referral (n=32, 40.5%) had an increased odds ratio (OR) of having microbiology with limited antimicrobial options compared to those undergoing primary osteomyelitis excision (OR: 3.8, 95% CI 1.2 – 11.2, P=0.023, Fisher's exact test). Conclusions. Patients are frequently referred with limited microbiological information. Pre-referral microbiology in long bone osteomyelitis correlated with intra-operative samples taken at our centre in less than one quarter of cases. Pre-referral microbiology data should be used with caution for planning treatment in osteomyelitis. Previous surgery for osteomyelitis was associated with microbiology culture with limited antimicrobial treatment options


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_8 | Pages 9 - 9
10 May 2024
Owen D
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Background. Increasing evidence suggests a link between the bearing surface used in total hip arthroplasty (THA) and the occurrence of infection. It is postulated that polyethylene has immunomodulatory effects and may influence bacterial function and survival, thereby impacting the development of periprosthetic joint infection (PJI). This study aimed to investigate the association between polyethylene type and revision surgery for PJI in THA using data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). We hypothesized that the use of XLPE would demonstrate a statistically significant reduction in revision rates due to PJI compared to N-XLPE. Methods. Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) spanning September 1, 1999, to December 31, 2021, were used to compare the infection revision rates between THA using N-XLPE and XLPE. We calculated the Cumulative Percentage Revision rate (CPR) and Hazard Ratio (HR) while controlling for factors like age, sex, body mass index (BMI), American Society of Anesthesiologists’ (ASA) grade, and head size. Results. From the total 361,083 primary THAs, 26,827 used N-XLPE and 334,256 used XLPE. Excluding data from the first 6 months post-surgery, 220 revisions occurred in the N-XLPE group and 1,055 in the XLPE group for PJI. The HR for infection revision was significantly higher in N-XLPE compared to XLPE, at 1.64 (95% CI, 1.41–1.90, p<0.001). Conclusions. This analysis provides evidence of an association between N-XLPE and revision for infection in THA. We suspect that polyethylene wear particles contribute to the susceptibility of THA to PJI, resulting in a significantly higher risk of revision for infection in N-XLPE hips compared to those with XLPE. Level of Evidence. Therapeutic Level III


Shoulder septic arthritis is uncommon and frequently misdiagnosed, resulting in severe consequences. This study evaluated the demographics, bacteriological profile, antibiotic susceptibility, treatment regimens, and clinical outcomes. This is a 10-year retrospective observational analysis of 30 patients (20 males and 10 females) who were treated for septic arthritis of the shoulder. The data collecting process utilised clinical records, laboratory archives, and x-ray archives. We gathered demographic information, pre- and post-intervention clinical data, serum biochemical markers, and the results of imaging examinations. All patients had a surgical arthrotomy and joint debridement in the operating room, and specimens were taken for culture and sensitivity testing. The specimens were cultivated for at least seventy-two hours. Shoulder joint ranges of motion, comorbidities, and the presence of osteomyelitis were assessed clinically to determine the outcome. All statistical analyses were conducted using the STATA 17 statistical software. Analysis of correlation between categorical variables was performed using the chi-squared test. The majority of the study patients were black Africans (97%). The age range of the group was from 8 days to 17 years. At presentation, 33% of patients had a low-grade fever, whereas the majority (60%) had normal body temperature. The average length of symptoms was 3.9 days (ranged from 1 day to 15 days), and the majority of patients had an increased white cell count (83%) and C-reactive protein (98%). There was accumulation of fluid in the joint of all individuals who received shoulder ultrasound imaging. We noted a significant incidence of gram-positive cocci, which were mostly susceptible to first-line antibiotics. Shoulder stiffness affected 63% of patients and chronic osteomyelitis affected 50% of individuals. Neither the severity nor the duration of the symptoms was related to an increased risk of osteomyelitis. The results of this study revealed that the clinical characteristics and bacterial profile of septic arthritis of the shoulder conform to typical patterns. The likelihood of osteomyelitis and an unfavourable prognosis is considerable


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 6 - 6
24 Nov 2023
Soares F Santos INM Seriacopi LS Durigon TS Cunha CC Dell Aquila AM Salles M
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Aim. Currently, gram-negative bacteria (GNB), including multidrug-resistant (MDR-GNB) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). To characterize the antimicrobial resistance patterns of Gram-negative bacteria (GNB) causing hip prosthetic joint infections in elderly patients treated at a Brazilian tertiary academic hospital. Method. This is a retrospective, cross-sectional study of patients over 60 years of age undergoing hip arthroplasty from 2018 to 2023 at a tertiary academic trauma, which were diagnosed with hip prosthetic joint infection. PJI diagnosed was based on EBJIS criteria, in which intraoperative tissue cultures identified the pathogens. Demographics, reason for arthroplasty, type of implant and susceptibility patterns using disk diffusion method were analysed. Results. Overall, among 17 elderly patients diagnosed with hip infected arthroplasty, 45 bacterial isolated were identified. Debridement, irrigation, antibiotic and implant retention (DAIR) procedures due to uncontrolled infection occurred in 47.0% (n=8/17), and five patients underwent more than two DAIR surgeries. Tissue cultures yielded eleven different bacterial species, with GNB accounted for 64.4% (n=29/45) of pathogens. Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa were identified in 34.5% (n=10/29), 17.25% (n=5/29), 13.8% (n=4/29), and 13.8% (n=4/29), respectively. In the resistance profile analysis, E. coli was most sensitive to antibiotics, whereas K. pneumoniae showed resistance rates higher than 70% for cephalosporins, carbapenems, and quinolones. All A. baumannii isolates were resistant to meropenem, and 80% of these isolates were resistant to amikacin. Conclusions. This study emphasizes the role of GNB in the microbiological profile of PJI among elderly patients at a tertiary hospital in a Brazilian centre. The present study portrays a worryingly higher rates of MDR-GNB, mainly to quinolones and cephalosporins resistance which have been the cornerstone of PJI antibiotic treatment. In addition, higher rates carbapenems and aminoglycosides resistance shows a threat to antibiotic treatment of PJI. More global studies need to be carried out to show a likely change in the microbial epidemiology of PJI


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 78 - 78
24 Nov 2023
Bernaus M Carmona F De Espinosa Vázquez de Sola JML Valentí A Abizanda G Cabodevilla AR Torres D Calero JA Font L Del Pozo JL
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Aim. To provide proof of concept in an in vivo animal model for the prevention of prosthetic joint infection prevention using electric fields along with conventional antibiotic prophylaxis. Corresponding Author: Marti Bernaus. Method. First, we standardized the animal model to simulate implant contamination during the surgical procedure. We then implanted cobalt-chrome prostheses adapted to both knees of two New Zealand White rabbits, under standard aseptic measures and antibiotic prophylaxis with cefazolin. Prior to implantation, we immersed the prostheses in a 0.3 McFarland inoculum of S. aureus (ATCC 25923) for 30 seconds. In the first animal (control), the joint was directly closed after washing with saline. In the second animal (case), both prostheses were treated with electric current pulses for 30 seconds, washed with saline, and the joint was closed. After 72 hours, both animals were reoperated for the collection of periprosthetic tissue and bone samples, and prosthesis removal. In all samples, we performed quantitative cultures prior to vortexing and sonication, as well as prolonged cultures of the sonication broth. We confirmed the absence of contamination by identification with MALDI-TOF (VITEK-MS) and automated antibiotic susceptibility testing of the isolated colonies (VITEK-2). Results. In the “control” animal, we isolated S. aureus in all studied samples. The bacterial count expressed as log10 (cfu/cm2) in the prostheses of the right and left legs was 9.38 and 8.86, respectively. The bacterial count expressed as log10 (cfu/mL) in bone and periprosthetic tissue biopsies was 2.70 and 2.72 in the right leg and 3.24 and 3.87 in the left leg, respectively. In the “case” animal, where an electric field was applied to the implant after placement in addition to cefazolin prophylaxis, all samples (prosthesis, bone, and periprosthetic tissue) were negative, and no isolation of the inoculated strain of S. aureus was obtained after incubation of the sonication broth for 14 days. Conclusions. This in vivo model suggests the potential effectiveness of applying an electric field to a prosthetic implant in combination with cefazolin for the prevention of PJI development, after exposure of the implant to an inoculum of S. aureus (ATCC 25923). Our findings need to be confirmed using a larger sample size