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We report microbiological results from a cohort of recurrent bone and joint infection to define the contributions of microbial persistence or replacement. We also investigated for any association between local antibiotic treatment and emerging antimicrobial resistance. Microbiological cultures and antibiotic treatments were reviewed for 125 individuals with recurrent infection (prosthetic joint infection, fracture-related infection, and osteomyelitis) at two UK centres between 2007 and 2021. At re-operation, 48/125 (38.4%) individuals had an organism from the same bacterial species as at their initial operation for infection. In 49/125 (39.2%), only new species were isolated in culture. In 28/125 (22.4%), re-operative cultures were negative. The most commonly persistent species were Staphylococcus aureus (46.3%), coagulase-negative Staphylococci (50.0%), and Pseudomonas aeruginosa (50.0%). Gentamicin non-susceptible organisms were common, identified at index procedure in 51/125 (40.8%) and at re-operation in 40/125 (32%). Gentamicin non-susceptibility at re-operation was not associated with previous local aminoglycoside treatment (21/71 (29.8%) vs. 19/54 (35.2%); p = 0.6). Emergence of new aminoglycoside resistance at recurrence was uncommon and did not differ significantly between those with and without local aminoglycoside treatment (3/71 (4.2%) vs. 4/54 (7.4%); p = 0.7). Culture-based diagnostics identified microbial persistence and replacement at similar rates in patients who re-presented with infection. Treatment for orthopaedic infection with local antibiotics was not associated with the emergence of specific antimicrobial resistance.

Background: It remains unclear how accurately patients’ previous microbiology correlates with that ascertained from deep sampling in long bone infection. This study assessed the quality of microbiology referral information and compared it to the gold standard of intra-operative deep tissue sampling. Methods: All patients referred to a single specialist centre within the UK between January 2019 and March 2020 who received surgery for long bone infection were eligible for inclusion. Data on microbiological testing that was performed prior to referral was collected prospectively at the time of clinic appointment and prior to surgery. Pre-referral microbiology was compared to microbiology from deep tissue samples taken during surgery. Results: 141 patients met the diagnostic criteria for long bone infection and were included for analysis. Of these, 72 patients had microbiological information available at referral from 88 samples, obtained from either sinus swab (n = 40), previous surgical sampling (n = 25), biopsy (n = 19) or blood cultures (n = 4). In 65.9% of samples, pre-referral microbiology was deemed to be a non-match when compared to intra-operative samples. Factors that increased risk of a non-match included presence of a sinus (odd’s ratio (OR) 11.3 [95% CI 2.84–56.6], p = 0.001), increased duration of time from sampling (OR 2.29, [95% CI 1.23–5.90], p = 0.030) and results from prior surgical sampling (OR 23.0 [95% CI 2.80–525.6], p = 0.011). Furthermore, previous surgical debridement gave an increased risk of multi-, extensively or pan-resistant isolates cultured from intra-operative sampling (OR 3.6 [95% CI 1.5–8.7], p < 0.01). Conclusions: We have demonstrated that presence of a sinus, a long time from the sample being taken and results from prior surgical sampling are more likely to give inaccurate representation of current microbiology. Importantly, in cases with previous debridement surgery, there was an increased risk of multi drug resistant isolates which should be planned for in future treatments.

This international, multi-center study evaluated the effect of antibiotic-loaded carriers (ALCs) on outcome in patients with a fracture-related infection (FRI) and evaluated whether bacterial resistance to the implanted antibiotics influences their efficacy. All patients who were retrospectively diagnosed with FRI according to the FRI consensus definition, between January 2015 and December 2019, and who underwent surgical treatment for FRI at any time point 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 ALCs and recurrence rate of FRI at 12 months and 24 months. Overall, 429 patients with 433 FRIs were included. A total of 251 (58.0%) cases were treated with ALCs. Gentamicin was the most frequently used antibiotic (247/251). Recurrence of infection after surgery occurred in 25/251 (10%) patients who received ALCs and in 34/182 (18.7%) patients who did not (unadjusted hazard ratio (uHR): 0.48, 95% CI: [0.29–0.81]). Resistance of cultured microorganisms to the implanted antibiotic was not associated with a higher risk of recurrence of FRI (uHR: 0.75, 95% CI: [0.32–1.74]). The application of ALCs in treatment of FRI is likely to reduce the risk of recurrence of infection. The high antibiotic concentrations of ALCs eradicate most pathogens regardless of susceptibility test results.

This international, multi-center study investigated the effect of individual components of surgery on the clinical outcomes of patients treated for fracture-related infection (FRI). All patients with surgically treated FRIs, confirmed by the FRI consensus definition, were included. Data were collected on demographics, time from injury to FRI surgery, soft tissue reconstruction, stabilization and systemic and local anti-microbial therapy. Patients were followed up for a minimum of one year. In total, 433 patients were treated with a mean age of 49.7 years (17–84). The mean follow-up time was 26 months (range 12–72). The eradication of infection was successful in 86.4% of all cases and 86.0% of unhealed infected fractures were healed at the final review. In total, 3.3% required amputation. The outcome was not dependent on age, BMI, the presence of metalwork or time from injury (recurrence rate 16.5% in FRI treated at 1–10 weeks after injury; 13.1% at 11–52 weeks; 12.1% at >52 weeks: p = 0.52). The debridement and retention of a stable implant (DAIR) had a failure rate of 21.4%; implant exchange to a new internal fixation had a failure rate of 12.5%; and conversion to external fixation had a failure rate of 10.3% (adjusted hazard ratio (aHR) DAIR vs. Ext Fix 2.377; 95% C.I. 0.96–5.731). Tibial FRI treated with a free flap was successful in 92.1% of cases and in 80.4% of cases without a free flap (HR 0.38; 95% C.I. 0.14–1.0), while the use of NPWT was associated with higher recurrence rates (HR 3.473; 95% C.I. 1.852–6.512). The implantation of local antibiotics reduced the recurrence from 18.7% to 10.0% (HR 0.48; 95% C.I. 0.29–0.81). The successful treatment of FRI was multi-factorial. These data suggested that treatment decisions should not be based on time from injury alone, as other factors also affected the outcome. Further work to determine the best indications for DAIR, free flap reconstruction and local antibiotics is warranted.

Fracture-related infections (FRIs) are classically considered to be early (0–2 weeks), delayed (3–10 weeks) or late (>10 weeks) based on hypothesized differences in causative pathogens and biofilm formation. Treatment strategies often reflect this classification, with debridement, antimicrobial therapy and implant retention (DAIR) preferentially reserved for early FRI. This study examined pathogens isolated from FRI to confirm or refute these hypothesized differences in causative pathogens over time. Cases of FRI managed surgically at three centres between 2015–2019 and followed up for at least one year were included. Data were analysed regarding patient demographics, time from injury and pathogens isolated. Patients who underwent DAIR were also analysed separately. In total, 433 FRIs were studied, including 51 early cases (median time from injury of 2 weeks, interquartile range (IQR) of 1–2 weeks), 82 delayed cases (median time from injury of 5 weeks, IQR of 4–8 weeks) and 300 late cases (median time from injury of 112 weeks, IQR of 40–737 weeks). The type of infection was associated with time since injury; early or delayed FRI are most likely to be polymicrobial, whereas late FRIs are more likely to be culture-negative, or monomicrobial. Staphylococcus aureus was the most commonly isolated pathogen at all time points; however, we found no evidence that the type of pathogens isolated in early, delayed or late infections were different (p = 0.2). More specifically, we found no evidence for more virulent pathogens (S. aureus, Gram-negative aerobic bacilli) in early infections and less virulent pathogens (such as coagulase negative staphylococci) in late infections. In summary, decisions on FRI treatment should not assume microbiological differences related to time since injury. From a microbiological perspective, the relevance of classifying FRI by time since injury remains unclear.