Aim. Local antibiotic treatment for bone and joint infections offers direct delivery of high concentrations of antibiotics with reduced systemic exposure and favourable safety profile. However, the possibility of prolonged release of antibiotics at sub-therapeutic levels creates concern about the possible development of antimicrobial resistance. We investigated patients with recurrent bone and joint infection for evidence of antimicrobial resistance emerging from the use of local antibiotics. Method. 125 patients with recurrent infection (prosthetic joint infection, fracture related infection and osteomyelitis) in the UK between 2007 and 2021 were identified. Electronic patient records (including operative notes, pathology results and prescriptions) were reviewed to extract site of infection, date of surgery, the use of local antibiotics, culture results, empiric and definitive antibiotic therapy. All antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary guidelines (BSAC and EUCAST). Results. Local antibiotics were used in 74/125 (59.2%) of patients. Agents used were Gentamicin 53/125 (42.4%), Tobramycin 18/125 (14.4%), and vancomycin in 19/125 (15.2%). Combined gentamicin and vancomycin usage was seen in 16/125 patients (12.8%). Gentamicin non-sensitivity was common in this cohort with frequent aminoglycoside use. At index procedure, a Gentamicin non-sensitive organism was cultured in 51/125 patients (40.8%). At re-operation this proportion was lower: 40/125 (32%). There was no statistically significant difference in the rate of Gentamicin resistance at reoperation comparing patients who previously received local aminoglycosides with those who had not (21/71, 29.8% vs 19/54, 35.2% p=0.6, chi-squared test). In 48/125 (38.4%) of patients, the same species was isolated during the index and recurrence surgery. We identified 7 cases with new aminoglycoside resistance arising at the second procedure. In 2/7 – S. aureus and E. faecalis - aminoglycoside resistance was the only change in antimicrobial sensitivity. In 5/7, there were at least 2 additional changes in observed antimicrobial sensitivity. 3/74 (4%) of cases who initially received local aminoglycoside cultured organisms with aminoglycoside resistance at recurrence. 4/51 (7.8%) of those who did not receive local or systemic aminoglycoside at index surgery cultured resistant organisms (chi square 0.82; p=0.365). Conclusions. As a group, patients whose treatment for orthopaedic infection included local antibiotics did not exhibit higher rates of specific antimicrobial resistance compared with those not treated with local antibiotics. However we did identify cases where Gram positive bacteria developed aminoglycoside resistance regardless of their initial antimicrobial therapy. This should be considered in antimicrobial choice during surgery for recurrence

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI. Cite this article: Bone Joint J 2022;104-B(5):575–580

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

Aim. Antimicrobial resistance (AMR) aggravates an already difficult treatment of periprosthetic joint infections (PJI). The prevalence of drug-resistant pathogens varies across countries and increases over time. Regular monitoring of bacteriological analyses should be performed. Due to many factors influencing the AMR, the correct choice of antimicrobial management remains arguable. The primary purpose of this retrospective study was to identify and compare causative bacteria and to compare the incidence of antibiotic resistance between the septic revision total knee arthroplasty (TKA) and septic revision total hip arthroplasty (THA). Method. A review of all revision TKAs and revision THAs, undertaken between 2007 and 2020 in a tertiary referral centre, was performed. Included were cases meeting the consensus criteria for PJI, in which an organism has been identified. There were no major differences in tissue sampling between revision TKAs and revision THAs over time. Results. A total of 228 bacterial strains, isolated after revision TKA and THA, were analysed for their resistance to 20 different antibiotics. There was a statistically significant higher occurrence of Gram-negative bacteria (p=0.002) and Enterococcus species (p=0.026) identified after revision THAs compared to TKA. The comparison of antibiotic resistance between revision TKAs and revision THAs was statistically significant in 9 of 20 analysed antibiotics. Pathogens isolated after revision THA were much more resistant compared to pathogens isolated after revision TKA. Resistance in revision THAs was significantly higher to oxacillin (p=0.03), ciprofloxacin (p<0.001), levofloxacin (p<0.001), moxifloxacin (p=0.005), clindamycin (p<0.001), co-trimoxazole (p<0.001), imipenem (p=0.01), rifampicin (p=0.005) and tetracycline (p=0.009). There was no significantly higher resistance of pathogens isolated after revision TKAs detected. No statistically significant difference in antibiotic resistance of Gram-negative bacteria between revision TKA and revision THA was observed. Conclusions. The occurrence and the resistance of bacteria to antibiotics differs significantly between revision TKAs and revision THAs. This has implications on of the choice of empirical antibiotic in revision surgery as well as prophylactic antibiotic in primary surgery, depending on the joint that is to be replaced

The worldwide increase in the resistance of micro-organisms to antimicrobial drugs leads to an increase in morbidity, mortality and health care costs. It is important to identify the resistant organisms, to provide alternative antibiotic treatment protocols and to identify the high-risk infection areas.

We undertook a retrospective study of 693 musculoskeletal infections seen in the Musculoskeletal Tumour and Sepsis Unit of Pretoria Academic Hospital over five years, capturing data relating to the microscopy, culture and sensitivity to antimicrobial drugs of micro-organisms from tissue samples and pus swabs.

Most infections developed in patients aged 31 to 40 years. Sepsis most often occurred postoperatively. The next most common sepsis followed trauma. The femur was the most common site, followed by the tibia and the knee. In descending order, the most common organisms isolated were Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas sp., Escherichia coli, Enterobacter sp.

In the last two years there was an alarming increase in coagulase-negative staphylococci. All micro-organisms exhibited increased resistance to specific antimicrobial drugs over the five-year period.

Aims

There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).

Aim. Metagenomic nanopore sequencing is demonstrating potential as a tool for diagnosis of infections directly from clinical samples. We have previously shown nanopore sequencing can be used to determine the causative bacterial species in prosthetic joint infections (PJI). However, to make predictions regarding antimicrobial resistance, human DNA contamination must be reduced so a greater proportion of sequence data corresponds to the microbial portion of the DNA extract. Here, we utilise selective DNA extraction from sonication fluid samples to begin to make predictions regarding antimicrobial resistance in PJI. Method. We investigated host cell DNA depletion with 5% saponin selective human cell lysis followed by nuclease digestion. Subsequently, bacterial cells were mechanically lysed before DNA extraction. Sequencing libraries from samples treated with and without saponin were prepared with a Rapid PCR Barcoding Kit. 1. and sequenced in multiplexes of 2–8 samples/flowcell on a GridION. Sequencing reads were analysed using the CRuMPIT pipeline and thresholds to indicate presence of a specific bacterial genus/species were investigated. Antimicrobial resistance determinants were detected using previously published sequences specifically for Staphylococcus aureus, as an example organism frequently causing PJI. Results. 247 DNA extracts from 115 sonication fluids plus controls were subjected to metagenomic sequencing, comprising extracts from 67 culture-positive (10 of which were culture-positive at <50 CFU/ml) and 48 culture-negative samples. 5% saponin depleted human DNA contamination, reducing the number of human sequenced bases to a median 12% from 98% in comparison to 5μm filtration without saponin. In 11 samples 5% saponin depleted human bases by <12% in comparison to 5μm filtration, which may be indicative of incomplete depletion. Bacteria observed in sonication fluid culture were identified to species-level in 49/65 (75%) cases, and to genus-level in 51/65 (78%). Specificity of sequencing was 103/114 (90%). Sequencing made a completely successful prediction of antimicrobial susceptibility in 8/19 S. aureus culture-positive samples treated with 5% saponin, and a partial prediction in 5/19 for the 8 antibiotics investigated. Without 5% saponin treatment sequencing could only detect a limited number of AMR determinants in 3/19 samples. Sequencing correctly predicted 13/15 (87%) resistant and 74/74 (100%) susceptible phenotypes where sufficient sequence data were available. Conclusions. Nanopore metagenomic sequencing can provide species identification in PJI. Additionally, depletion of human DNA improves depth of coverage and allows detection of antimicrobial resistance determinants, demonstrating as a proof of principle that nanopore sequencing could potentially provide a complete diagnostic tool in PJI. 1. Oxford Nanopore Technologies

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

Prosthetic Joint Infection (PJI) is a devastating complication that can occur after total joint replacement surgery. With increasing antimicrobial resistance, there is a need for non-antibiotic approaches to treat and prevent PJI. Doping calcium phosphates with antimicrobial ions shows promise for these purposes. This systematic review aims to search and summarise the evidence-base for the potential of calcium phosphates doped with different antimicrobial ions. A systematic review was conducted on PubMed, Embase, Web-Of-Science, Cochrane Library and Emcare of in vitro and animal studies on the antimicrobial activity of (co)substituted calcium phosphates according to PRIMSA guidelines.. The research protocol, listing search terms and in/exclusion criteria, was registered a priori at . https://doi.org/10.7910/DVN/HEP18U. Data was extracted regarding ions, micro-organisms and antimicrobial activity. The search retrieved 1017 hits of which 148 papers were included. The substitution of 33 different ions was reported. Silver (n= 46), zinc (n=39), copper (n=18) and magnesium (n=14) were the most commonly doped ions. 36 different micro-organisms were studied of which E. coli (n=109), S. aureus (n=99), and C. albicans (n=22) were the most common. 6 different outcomes were reported, most commonly the K-ratio (n=53), the log CFU (n=41) and the bacterial inhibition zone (n=39). A validated outcome for the evaluation of biofilm prevention was lacking. There was considerable heterogeneity in studied ions, micro-organisms and reported outcomes. A lack of clearly defined reporting guidelines in the field of antimicrobial materials has led to the use of clinically irrelevant micro-organisms and a general lack of consistency of the methods used and the reported results. Currently, there is no universally accepted measure for the effectiveness required from biomaterials for treatment and prevention of PJI

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

Introduction. In specific conditions, infection may lead to bone loss and is difficult to treat. 1. Current clinical approaches rely on the introduction of antibiotics. While these may be effective, there are concerns regarding the rise of antimicrobial resistance. There is therefore interest in the development of antimicrobial bone graft substitutes for dental and trauma surgery. Aim & Objectives. The incorporation of zinc into biomaterials has been shown to confer broad spectrum antimicrobial activity, but this has not yet been applied to the development of a commercial bone graft substitute. The aim of this research was therefore to prepare and characterise a series of zinc-substituted nanoscale hydroxyapatite (nHA) materials, including evaluation of antimicrobial activity. Method. Zinc (Zn) substituted nHA materials were prepared (0, 5, 10, 15 & 20 mol.% Zn) using a wet chemical precipitation method with a rapid mixing. (2). The reaction was carried out using zinc hydroxide at pH 10. The suspension formed was washed and dried into both powder & paste forms. The resultant powders were characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). The antimicrobial activity was evaluated against Staphylococcus aureus (S8650 strain - isolated from an osteomyelitis case), by two techniques. The Miles and Misra method was applied to determine the number of colony-forming units (CFUs) in bacterial suspensions incubated with pastes. Secondly, a biofilm initialization method was used to evaluate the capacity of the materials to prevent biofilm formation. One-way analysis of variance (ANOVA) was used for the statistical analysis and results with p-value < 0.05 were considered statistically significant. Results. XRD indicated the formation of pure hydroxyapatite with up to 10 mol.% Zn without any side products. However, when Zn was increased to 15 & 20 mol %, zinc oxide (ZnO) peaks were detected. The TEM showed nanoscale needle-like particles when Zn was increased compared to nHA particles. Regarding the antibacterial activity, ZnHA pastes at all concentrations caused a significant reduction in bacterial CFUs in a dose-dependent manner (50, 100 & 200 mg). Additionally, even the lowest zinc substitution (5 mol.%) significantly reduced biofilm formation. Conclusion. The results demonstrated a novel method to produce a Zn-substituted nHA that showed antimicrobial activity against a pathogen isolated from a bone infection

Aim. Periprosthetic joint infection (PJI) is a severe complication after total joint arthroplasty. To prevent PJI, strict infection prevention measures are followed in combination with surgical antibiotic prophylaxis (SAP). To date, scientific reports concerning the optimal duration of SAP in revision arthroplasty are scarce. The aim of this multicenter open-label, randomized controlled trial in the Netherlands, is to investigate the superiority of 5 days (extended) versus a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip and knee. Method. Included patients with an assumed aseptic hip or knee revision procedure received a single dose of 2 or 3 gram cefazolin preoperatively. Patients were randomly assigned in a 1:1 ratio to receive extended prophylaxis of cefazolin during 5 days postoperatively versus no prophylaxis after wound closure. Patients were excluded if evidence of PJI at revision. The primary endpoint was the incidence of PJI within one year after revision arthroplasty. PJI was defined according to the 2018 Philadelphia consensus criteria. With a sample size of 746 patients, an alpha of 5% and a power of 80%, superiority of the extended regimen would be shown if the lower boundary of the 95% confidence interval (CI) of the absolute between-group difference of the percentage of PJI is below −4%. Results. In total 751 patients were included for analysis: 379 in the single dose cefazolin group and 372 in the extended group. Within one year, PJI occurred in 2.6% (10/379) in the single dose group and 2.4% (9/372) in the extended group (risk difference, −0.2 percentage points; 95% CI, −2.5 to 2.0%), thus superiority was not shown. Adverse drug events were seen in 20 cases with extended and 7 cases with a single dose prophylaxis. Conclusions. Extended prophylaxis is not significantly superior to a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip or knee. This is the first randomized controlled trail in which the duration of SAP in the selected group of patients undergoing revision arthroplasty was studied. Extending SAP after closure of the wound could increase the selection or induction of antimicrobial resistance, has an increased risk for adverse drug events, and is therefore not in line with the primary goal of antimicrobial stewardship, comprising optimizing clinical outcomes and ensuring cost-effective therapy while minimizing unintended consequences of antimicrobial use

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

Periprosthetic joint infections (PJI) are challenging complications following arthroplasty. Staphylococci are a frequent cause of PJI and known biofilm producers. Reoperations for PJI of the hip or knee between 2012 and 2015 performed at Sahlgrenska University Hospital were identified. Medical records were reviewed, and clinical parameters recorded for patients whose intraoperative bacterial isolates had been stored at the clinical laboratory. Staphylococcal strains isolated from reoperations due to first-time PJI were characterised by their ability to form biofilms using the microtiter plate test. The study group included 49 patients (70 bacterial strains) from first-time PJI, whereof 24 (49%) patients had recurrent infection. Strong biofilm production was significantly associated with recurrent infection. Patients infected with strong biofilm producers had a five-fold increased risk for recurrent infection. Strong biofilm production was significantly associated with increased antimicrobial resistance and PJI recurrence. This underscores the importance of determining biofilm production and susceptibility as part of routine diagnostics in PJI. Strong staphylococcal biofilm production may have implications on therapeutic choices and suggest more extensive surgery. Furthermore, despite the increased biofilm resistance to rifampicin, results from this study support its use in staphylococcal PJI

Aims. Tuberculosis (TB) is one of the biggest communicable causes of mortality worldwide. While incidence in the UK has continued to fall since 2011, Bradford retains one of the highest TB rates in the UK. This study aims to examine the local disease burden of musculoskeletal (MSK) TB, by analyzing common presenting factors within the famously diverse population of Bradford. Methods. An observational study was conducted, using data from the Bradford Teaching Hospitals TB database of patients with a formal diagnosis of MSK TB between January 2005 and July 2017. Patient data included demographic data (including nationality/date of entry to the UK), disease focus, microbiology, and management strategies. Disease incidence was calculated using population data from the Office for National Statistics. Poisson confidence intervals were calculated to demonstrate the extent of statistical error. Disease incidence and nationality were also analyzed, and correlation sought, using the chi-squared test. Results. Between January 2005 and July 2017, 109 cases of MSK TB were diagnosed in Bradford. Mean incidence was 1.65 per 100,000 population, per calendar year (SD 0.75). A total of 38 cases required surgical intervention. Low rates of antimicrobial resistance were encountered. A low rate of loss to follow-up was observed (four patients; 3.7%). Overall, 94.5% of patients (n = 103) were successfully treated. 67% of patients (n = 73) reported their country of origin as either India, Pakistan, or Bangladesh. These ethnicities account for around 25% of the local population. Conclusion. Bradford maintains a high prevalence of MSK TB infection relative to national data; the prevalence within the local immigrant population remains grossly disproportionate. Typical associated factors (HIV/hepatitis coinfection, drug resistance), have only modest prevalence in our dataset. However, local socioeconomic factors such as deprivation and poverty appear germane as suggested by global literature. We advocate a high degree of suspicion in treatment of atypical infection in any area with similar population factors to ensure timely diagnosis. Cite this article: Bone Jt Open 2022;3(5):432–440

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

Aim. 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

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. Periprosthetic joint infection (PJI) is a feared complication of total joint arthroplasty of hip (THA) or knee (TKA). Debridement, antibiotic treatment, and implant retention (DAIR) is an effective treatment of early PJI. In the Netherlands, cefazolin resistance in early PJI after primary arthroplasty is low. Little is known about causative micro-organisms and resistance patterns in PJI after revision arthroplasty. No recommendations for empirical treatment are described in the current guidelines. The aim of this study is to describe the characteristics of PJI after revision arthroplasty and to evaluate whether the used empirical treatment regimens are adequate, based on microbiology data. Method. In this retrospective study we included patients with early PJI after aseptic revision of THA or TKA, treated with DAIR between 2012 and 2020. Success rate was defined as implant retention and no persistent or recurrent infection during one year follow-up. Results. We identified 96 patients with PJI. PJI was most frequently caused by Staphylococcus spp. (n=73), Gram-negative bacilli (n=31) or Enterococcus spp. (n=13). Polymicrobial infection was diagnosed in 38 PJIs. Mismatches were present in 72 (75%) of the PJIs (95% CI: 0.66–0.84). Table 1 shows the number of mismatches per empirical treatment regimen. Figure 1 shows the responsible micro-organisms for the mismatches. Success rate of PJI treatment was significant reduced for patients with mismatching compared to matching empirical therapy: 62% vs. 95% respectively (OR: 0.09, 95% CI: 0.01–0.68, p=0.004). If vancomycin would have been the empirical treatment, mismatches would have been reduced to 31 (32%) (95% CI: 0.23–0.42). With vancomycin-ciprofloxacin combination therapy the mismatches would have been reduced to 1% (95% CI: −0.01–0.03). Conclusions. There is a high number of mismatches in empirical treatment in early PJI after revision arthroplasty, which have significant influence on the outcome. Based on our data cefazolin should not be recommended as empirical treatment for this specific group. Our data shows that review of local data is necessary to improve treatment strategies, that eventually might improve outcome. Besides changing Gram-positive coverage, a prospective study is needed to assess the benefits of broader spectrum empiric antimicrobial treatment taken into account toxicity and other side effects such as antimicrobial resistance. For any tables or figures, please contact the authors directly