Does the Use of Local Antibiotics Affect Clinical Outcome of Patients with Fracture-Related Infection?

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.

Causative Pathogens Do Not Differ between Early, Delayed or Late Fracture-Related Infections.

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.

Pre-Referral Microbiology in Long Bone Infection: What Can It Tell Us?

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.

Can we predict outcome after treatment of long bone osteomyelitis?

AIMS: This study presents patient-reported quality of life (QoL) over the first year following surgical debridement of long bone osteomyelitis. It assesses the bone involvement, antimicrobial options, coverage of soft tissues, and host status (BACH) classification as a prognostic tool and its ability to stratify cases into 'uncomplicated' or 'complex'. METHODS: Patients with long-bone osteomyelitis were identified prospectively between June 2010 and October 2015. All patients underwent surgical debridement in a single-staged procedure at a specialist bone infection unit. Self-reported QoL was assessed prospectively using the three-level EuroQol five-dimension questionnaire (EQ-5D-3L) index score and visual analogue scale (EQ-VAS) at five postoperative time-points (baseline, 14 days, 42 days, 120 days, and 365 days). BACH classification was applied retrospectively by two clinicians blinded to outcome. RESULTS: In total, 71 patients with long-bone osteomyelitis were included. There was significant improvement from time of surgery to one year postoperatively in mean EQ-VAS (58.2 to 78.9; p < 0.001) and mean EQ-5D-3L index scores (0.284 to 0.740; p < 0.001). At one year following surgery, BACH 'uncomplicated' osteomyelitis was associated with better QoL compared to BACH 'complex' osteomyelitis (mean EQ-5D-3L 0.900 vs 0.685; p = 0.020; mean EQ-VAS 87.1 vs 73.6; p = 0.043). Patients with uncomplicated bone involvement (BACH type B1, cavitary) reported higher QoL at all time-points when compared to complex bone involvement (B2, segmental or B3, osteomyelitis involving a joint). Patients with good antimicrobial options (Ax or A1) gave higher outcome scores compared to patients with multidrug-resistant isolates (A2). The need for microvascular tissue transfer (C1 and C2) did not impact significantly on QoL. Patients without major comorbidities (uncomplicated, H1) reported higher QoL compared to those with significant disease (complex, H2). CONCLUSION: Uncomplicated osteomyelitis, as defined by BACH, gave higher self-reported QoL when compared to complex cases. The bone involvement, antimicrobial options, and host status variables were able to stratify patients in terms of QoL. These data can be used to offer prognostic information to patients who are undergoing treatment for long bone osteomyelitis. Cite this article: Bone Joint J 2020;102-B(11):1587-1596.

Can we predict outcome after treatment of long bone osteomyelitis?

AIMS: This study presents patient-reported quality of life (QoL) over the first year following surgical debridement of long bone osteomyelitis. It assesses the bone involvement, antimicrobial options, coverage of soft tissues, and host status (BACH) classification as a prognostic tool and its ability to stratify cases into 'uncomplicated' or 'complex'. METHODS: Patients with long-bone osteomyelitis were identified prospectively between June 2010 and October 2015. All patients underwent surgical debridement in a single-staged procedure at a specialist bone infection unit. Self-reported QoL was assessed prospectively using the three-level EuroQol five-dimension questionnaire (EQ-5D-3L) index score and visual analogue scale (EQ-VAS) at five postoperative time-points (baseline, 14 days, 42 days, 120 days, and 365 days). BACH classification was applied retrospectively by two clinicians blinded to outcome. RESULTS: In total, 71 patients with long-bone osteomyelitis were included. There was significant improvement from time of surgery to one year postoperatively in mean EQ-VAS (58.2 to 78.9; p < 0.001) and mean EQ-5D-3L index scores (0.284 to 0.740; p < 0.001). At one year following surgery, BACH 'uncomplicated' osteomyelitis was associated with better QoL compared to BACH 'complex' osteomyelitis (mean EQ-5D-3L 0.900 vs 0.685; p = 0.020; mean EQ-VAS 87.1 vs 73.6; p = 0.043). Patients with uncomplicated bone involvement (BACH type B1, cavitary) reported higher QoL at all time-points when compared to complex bone involvement (B2, segmental or B3, osteomyelitis involving a joint). Patients with good antimicrobial options (Ax or A1) gave higher outcome scores compared to patients with multidrug-resistant isolates (A2). The need for microvascular tissue transfer (C1 and C2) did not impact significantly on QoL. Patients without major comorbidities (uncomplicated, H1) reported higher QoL compared to those with significant disease (complex, H2). CONCLUSION: Uncomplicated osteomyelitis, as defined by BACH, gave higher self-reported QoL when compared to complex cases. The bone involvement, antimicrobial options, and host status variables were able to stratify patients in terms of QoL. These data can be used to offer prognostic information to patients who are undergoing treatment for long bone osteomyelitis.

Audio-visual distraction as an adjunct to standby anaesthesia in persons with paraplegia: a case series of five operations.

INTRODUCTION: Persons with paraplegia present complex challenges to anaesthetists. Complications experienced by these patients can require major orthoplastic surgery such as excision of infected bone and soft tissue due to pressure sores and soft tissue reconstruction. Anaesthetic strategies deemed both safe and acceptable to this population are essential. CASE PRESENTATION: We report a case series of five procedures in four patients with complete chronic spinal cord injury (CSCI) who underwent operations in lateral position under standby anaesthesia and audio-visual distraction (AVD) with minimal sedation. Patients' experience was formally assessed as part of the ongoing AVD service evaluation in our institution. All stated that they were not concerned in the operating theatre and felt "comfortable" or "very comfortable" throughout. All patients rated the experience as "better" than their previous experience with general anaesthesia and felt "very satisfied" with their anaesthetic. Importantly, all patients would recommend sedation with AVD to other patients. DISCUSSION: To our knowledge, this is the first report of AVD application as an adjunct to standby anaesthesia during major surgery in persons with paraplegia. Patient feedback was extremely positive, therefore it is likely that by making standby anaesthesia more acceptable to patients the use of AVD could reduce anaesthetic risk in this complex patient group.

Adhesion of Plasmodium falciparum-infected erythrocytes to human cells: molecular mechanisms and therapeutic implications.

Severe malaria has a high mortality rate (15-20%) despite treatment with effective antimalarial drugs. Adjunctive therapies for severe malaria that target the underlying disease process are therefore urgently required. Adhesion of erythrocytes infected with Plasmodium falciparum to human cells has a key role in the pathogenesis of life-threatening malaria and could be targeted with antiadhesion therapy. Parasite adhesion interactions include binding to endothelial cells (cytoadherence), rosetting with uninfected erythrocytes and platelet-mediated clumping of infected erythrocytes. Recent research has started to define the molecular mechanisms of parasite adhesion, and antiadhesion therapies are being explored. However, many fundamental questions regarding the role of parasite adhesion in severe malaria remain unanswered. There is strong evidence that rosetting contributes to severe malaria in sub-Saharan Africa; however, the identity of other parasite adhesion phenotypes that are implicated in disease pathogenesis remains unclear. In addition, the possibility of geographic variation in adhesion phenotypes causing severe malaria, linked to differences in malaria transmission levels and host immunity, has been neglected. Further research is needed to realise the untapped potential of antiadhesion adjunctive therapies, which could revolutionize the treatment of severe malaria and reduce the high mortality rate of the disease.