ABSTRACT
Diagnosis of orthopedic device-related infection is challenging, and causative pathogens may be difficult to culture. Metagenomic sequencing can diagnose infections without culture, but attempts to detect antimicrobial resistance (AMR) determinants using metagenomic data have been less successful. Human DNA depletion may maximize the amount of microbial DNA sequence data available for analysis. Human DNA depletion by saponin was tested in 115 sonication fluid samples generated following revision arthroplasty surgery, comprising 67 where pathogens were detected by culture and 48 culture-negative samples. Metagenomic sequencing was performed on the Oxford Nanopore Technologies GridION platform. Filtering thresholds for detection of true species versus contamination or taxonomic misclassification were determined. Mobile and chromosomal genetic AMR determinants were identified in Staphylococcus aureus-positive samples. Of 114 samples generating sequence data, species-level positive percent agreement between metagenomic sequencing and culture was 50/65 (77%; 95% confidence interval [CI], 65 to 86%) and negative percent agreement was 103/114 (90%; 95% CI, 83 to 95%). Saponin treatment reduced the proportion of human bases sequenced in comparison to 5-µm filtration from a median (interquartile range [IQR]) of 98.1% (87.0% to 99.9%) to 11.9% (0.4% to 67.0%), improving reference genome coverage at a 10-fold depth from 18.7% (0.30% to 85.7%) to 84.3% (12.9% to 93.8%). Metagenomic sequencing predicted 13/15 (87%) resistant and 74/74 (100%) susceptible phenotypes where sufficient data were available for analysis. Metagenomic nanopore sequencing coupled with human DNA depletion has the potential to detect AMR in addition to species detection in orthopedic device-related infection. Further work is required to develop pathogen-agnostic human DNA depletion methods, improving AMR determinant detection and allowing its application to other infection types.
Subject(s)
Anti-Bacterial Agents , Saponins , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , High-Throughput Nucleotide Sequencing/methods , Humans , Metagenome , Metagenomics/methodsABSTRACT
Current guidelines recommend collection of multiple tissue samples for diagnosis of prosthetic joint infections (PJI). Sonication of explanted devices has been proposed as a potentially simpler alternative; however, reported microbiological yield varies. We evaluated sonication for diagnosis of PJI and other orthopedic device-related infections (DRI) at the Oxford Bone Infection Unit between October 2012 and August 2016. We compared the performance of paired tissue and sonication cultures against a "gold standard" of published clinical and composite clinical and microbiological definitions of infection. We analyzed explanted devices and a median of five tissue specimens from 505 procedures. Among clinically infected cases the sensitivity of tissue and sonication culture was 69% (95% confidence interval, 63 to 75) and 57% (50 to 63), respectively (P < 0.0001). Tissue culture was more sensitive than sonication for both PJI and other DRI, irrespective of the infection definition used. Tissue culture yield was higher for all subgroups except less virulent infections, among which tissue and sonication culture yield were similar. The combined sensitivity of tissue and sonication culture was 76% (70 to 81) and increased with the number of tissue specimens obtained. Tissue culture specificity was 97% (94 to 99), compared with 94% (90 to 97) for sonication (P = 0.052) and 93% (89 to 96) for the two methods combined. Tissue culture is more sensitive and may be more specific than sonication for diagnosis of orthopedic DRI in our setting. Variable methodology and case mix may explain reported differences between centers in the relative yield of tissue and sonication culture. Culture yield was highest for both methods combined.
Subject(s)
Arthritis, Infectious/diagnosis , Biopsy , Prosthesis-Related Infections/diagnosis , Sonication , Aged , Arthritis, Infectious/microbiology , Arthritis, Infectious/pathology , Bacteriological Techniques/standards , Device Removal , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Prostheses and Implants/adverse effects , Prostheses and Implants/microbiology , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/pathology , Sensitivity and Specificity , Specimen Handling/standardsABSTRACT
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.
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Pressure-ulcer related pelvic osteomyelitis is managed with little high-quality evidence. We undertook an international survey of orthopedic surgical management, covering diagnostic parameters, multidisciplinary input, and surgical approaches (indications, timing, wound closure, and adjunctive therapies). This identified areas of consensus and disagreement, representing a starting point for future discussion and research.
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AIM: This study investigated the compliance with a guideline-based antibiotic regimen on the outcome of patients surgically treated for a fracture-related infection (FRI). METHOD: In this international multicenter observational study, patients were included when diagnosed with an FRI between 2015 and 2019. FRI was defined according to the FRI consensus definition. All patients were followed for at least one year. The chosen antibiotic regimens were compared to the published guidelines from the FRI Consensus Group and correlated to outcome. Treatment success was defined as the eradication of infection with limb preservation. RESULTS: A total of 433 patients (mean age 49.7 ± 16.1 years) with FRIs of mostly the tibia (50.6%) and femur (21.7%) were included. Full compliance of the antibiotic regime to the published guidelines was observed in 107 (24.7%) cases. Non-compliance was mostly due to deviations from the recommended dosing, followed by the administration of an alternative antibiotic than the one recommended or an incorrect use or non-use of rifampin. Non-compliance was not associated with a worse outcome: treatment failure was 12.1% in compliant versus 13.2% in non-compliant cases (p = 0.87). CONCLUSIONS: We report good outcomes in the treatment of FRI and demonstrated that minor deviations from the FRI guideline are not associated with poorer outcomes.
Subject(s)
Fractures, Bone , Humans , Adult , Middle Aged , Aged , Fractures, Bone/complications , Fractures, Bone/drug therapy , Fractures, Bone/surgery , Anti-Bacterial Agents/therapeutic use , Treatment Outcome , Consensus , Treatment FailureABSTRACT
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.
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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.
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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.
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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.
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Background: Classification systems for orthopaedic infection include patient health status, but there is no consensus about which comorbidities affect prognosis. Modifiable factors including substance use, glycaemic control, malnutrition and obesity may predict post-operative recovery from infection. Aim: This systematic review aimed (1) to critically appraise clinical prediction models for individual prognosis following surgical treatment for orthopaedic infection where an implant is not retained; (2) to understand the usefulness of modifiable prognostic factors for predicting treatment success. Methods: EMBASE and MEDLINE databases were searched for clinical prediction and prognostic studies in adults with orthopaedic infections. Infection recurrence or re-infection after at least 6 months was the primary outcome. The estimated odds ratios for the primary outcome in participants with modifiable prognostic factors were extracted and the direction of the effect reported. Results: Thirty-five retrospective prognostic cohort studies of 92â¯693 patients were included, of which two reported clinical prediction models. No studies were at low risk of bias, and no externally validated prediction models were identified. Most focused on prosthetic joint infection. A positive association was reported between body mass index and infection recurrence in 19 of 22 studies, similarly in 8 of 14 studies reporting smoking history and 3 of 4 studies reporting alcohol intake. Glycaemic control and malnutrition were rarely considered. Conclusion: Modifiable aspects of patient health appear to predict outcomes after surgery for orthopaedic infection. There is a need to understand which factors may have a causal effect. Development and validation of clinical prediction models that include participant health status will facilitate treatment decisions for orthopaedic infections.
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Fracture-related infection (FRI) is common and often diagnosed late.Accurate diagnosis is the beginning of effective treatment.Diagnosis can be difficult, particularly when there are no outward signs of infection.The new FRI definition, together with clear protocols for nuclear imaging, microbiological culture and histological analysis, should allow much better study design and a clearer understanding of infected fractures.In recent years, there has been a new focus on defining FRI and avoiding non-specific, poorly targeted treatment. Previous studies on FRI have often failed to define infection precisely and so are of limited value. This review highlights the essential principles of making the diagnosis and how clinical signs, serum tests, imaging, microbiology, molecular biology and histology all contribute to the diagnostic pathway. Cite this article: EFORT Open Rev 2020;5:614-619. DOI: 10.1302/2058-5241.5.190072.
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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.
Subject(s)
Osteomyelitis/therapy , Adult , Aged , Aged, 80 and over , Debridement , Female , Humans , Male , Middle Aged , Osteomyelitis/drug therapy , Osteomyelitis/microbiology , Osteomyelitis/surgery , Patient Reported Outcome Measures , Prognosis , Quality of Life , Risk Assessment , Single-Blind Method , Treatment Outcome , Young AdultABSTRACT
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.
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AIMS: The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition. METHODS: A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree. RESULTS: Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 109/l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases. CONCLUSION: The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article: Bone Joint J 2020;102-B(7):904-911.
Subject(s)
Biomarkers/blood , Fractures, Bone/blood , Surgical Wound Infection/blood , Adolescent , Adult , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Decision Trees , Female , Fractures, Bone/surgery , Humans , Leukocyte Count , Male , Middle Aged , Neutrophils , Retrospective Studies , Sensitivity and SpecificityABSTRACT
We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.82 [95%CI 3.45-6.72]). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (22.6% vs. 8.6% elsewhere) (aOR 2.47 [1.99-3.08]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.52 [1.07-2.16]) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit staff were relatively protected (0.44 [0.28-0.69]), likely by a bundle of PPE-related measures. Positive results were more likely in Black (1.66 [1.25-2.21]) and Asian (1.51 [1.28-1.77]) staff, independent of role or working location, and in porters and cleaners (2.06 [1.34-3.15]).
Subject(s)
Coronavirus Infections/epidemiology , Health Personnel/statistics & numerical data , Pneumonia, Viral/epidemiology , Adolescent , Adult , Age Factors , Aged , Asymptomatic Infections/epidemiology , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , Hospitals, Teaching/statistics & numerical data , Humans , Incidence , Infectious Disease Transmission, Patient-to-Professional/statistics & numerical data , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Risk , SARS-CoV-2 , Surveys and Questionnaires , United Kingdom/epidemiology , Young AdultABSTRACT
BACKGROUND: Orthopaedic infections, such as osteomyelitis, diabetic foot infection and prosthetic joint infection, are most commonly treated by a combination of surgical debridement and a prolonged course of systemic antibiotics, usually for at least 4-6 weeks. Use of local antibiotics, implanted directly into the site of infection at the time of surgery, may improve antibiotic delivery and allow us to shorten the duration of systemic antibiotic therapy, thereby limiting the frequency of side effects, cost and selection pressure for antimicrobial resistance. METHODS: SOLARIO is a multicentre open-label randomised controlled non-inferiority trial comparing short and long systemic antibiotic therapy alongside local antibiotic therapy. Adult patients with orthopaedic infection, who have given informed consent, will be eligible to participate in the study provided that no micro-organisms identified from deep tissue samples are resistant to locally implanted antibiotics. Participants will be randomised in a 1:1 ratio to receive either a short course (≤ 7 days) or currently recommended long course (≥ 4 weeks) of systemic antibiotics. The primary outcome will be treatment failure by 12 months after surgery, as ascertained by an independent Endpoint Committee blinded to treatment allocation. An absolute non-inferiority margin of 10% will be used for both per-protocol and intention-to-treat populations. Secondary outcomes will include probable and definite treatment failure, serious adverse events, treatment side effects, quality of life scores and cost analysis. DISCUSSION: This study aims to assess a treatment strategy that may enable the reduction of systemic antibiotic use for patients with orthopaedic infection. If this strategy is non-inferior, this will be to the advantage of patients and contribute to antimicrobial stewardship. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03806166. Registered on 11 November 2019.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Osteomyelitis/drug therapy , Prosthesis-Related Infections/drug therapy , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Diabetic Foot/complications , Diabetic Foot/drug therapy , HumansABSTRACT
OBJECTIVES: The aim of this study was to assess the clinical application of, and optimize the variables used in, the BACH classification of long-bone osteomyelitis. METHODS: A total of 30 clinicians from a variety of specialities classified 20 anonymized cases of long-bone osteomyelitis using BACH. Cases were derived from patients who presented to specialist centres in the United Kingdom between October 2016 and April 2017. Accuracy and Fleiss' kappa (Fκ) were calculated for each variable. Bone involvement (B-variable) was assessed further by nine clinicians who classified ten additional cases of long bone osteomyelitis using a 3D clinical imaging package. Thresholds for defining multidrug-resistant (MDR) isolates were optimized using results from a further analysis of 253 long bone osteomyelitis cases. RESULTS: The B-variable had a classification accuracy of 77.0%, which improved to 95.7% when using a 3D clinical imaging package (p < 0.01). The A-variable demonstrated difficulty in the accuracy of classification for increasingly resistant isolates (A1 (non-resistant), 94.4%; A2 (MDR), 46.7%; A3 (extensively or pan-drug-resistant), 10.0%). Further analysis demonstrated that isolates with four or more resistant test results or less than 80% sensitive susceptibility test results had a 98.1% (95% confidence interval (CI) 96.6 to 99.6) and 98.8% (95% CI 98.1 to 100.0) correlation with MDR status, respectively. The coverage of the soft tissues (C-variable) and the host status (H-variable) both had a substantial agreement between users and a classification accuracy of 92.5% and 91.2%, respectively. CONCLUSIONS: The BACH classification system can be applied accurately by users with a variety of clinical backgrounds. Accuracy of B-classification was improved using 3D imaging. The use of the A-variable has been optimized based on susceptibility testing results.Cite this article: A. J. Hotchen, M. Dudareva, J. Y. Ferguson, P. Sendi, M. A. McNally. The BACH classification of long bone osteomyelitis. Bone Joint Res 2019;8:459-468. DOI: 10.1302/2046-3758.810.BJR-2019-0050.R1.
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AIM: This study quantified changes in the microbiology of osteomyelitis over a ten year period from a single centre within the UK with regard to infection with multi-drug resistant (MDR) bacteria and susceptibility of antimicrobial regimens. METHOD: Patients with chronic osteomyelitis undergoing definitive surgery from 2013-2017 were inluded (nâ¯=â¯223). Microbiology was compared to patients in a cohort from 2001-2004, using the same diagnostic criteria, and same deep tissue sampling technique (nâ¯=â¯157). Clinical features associated with MDR bacterial infection were analysed using logistic regression. RESULTS: Both cohorts had similar baseline characteristics. Despite a similar proportion of Staphylococcus aureus in both cohorts, the rate of methicillin resistant Staphylococcus aureus (MRSA) infection was lower in 2013-2017 compared to 2001-2004 (11.4% vs 30.8% of Staphylococcus aureus, pâ¯=â¯0.007). However, the proportion of MDR infections was similar in both cohorts (15.2% versus 17.2%). Metalwork was associated with MDR infection (unadjusted OR 5.0; 95% CI: 1.15 to 22.0). There was no change in resistance to glycopeptide / meropenem combination treatment (2.2% vs 2.5%, p > 0.9). CONCLUSIONS: In this centre, rates of MRSA osteomyelitis have fallen by two thirds, over the past 10 years, in line with the reducing rate of MRSA bacteraemia nationally. A history of metalwork may predict MDR infection. A glycopeptide with an anti-pseudomonal carbapenem remains the post-operative empiric systemic regimen of choice. Resistance patterns support the use of a glycopeptide with an aminoglycoside in local antibiotic therapy.
Subject(s)
Bacterial Infections/microbiology , Osteomyelitis/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/diagnosis , Bacterial Infections/drug therapy , Bacterial Typing Techniques , Chronic Disease , Cohort Studies , Combined Modality Therapy , Disease Management , Disease Susceptibility , Drug Resistance, Multiple, Bacterial , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Osteomyelitis/diagnosis , Osteomyelitis/therapy , Risk Factors , Symptom Assessment , Treatment Outcome , Young AdultABSTRACT
Background and Purpose: A case series review of chronic pelvic osteomyelitis treated with combined medical and surgical treatment by a multidisciplinary team. Methods: All patients treated with surgical excision of pelvic osteomyelitis at our tertiary referral centre between 2002 and 2014 were included. All received combined care from a clinical microbiologist, an orthopaedic surgeon and a plastic surgeon. The rate of recurrent infection, wound healing problems and post-operative mortality was determined in all. Treatment failure was defined as reoperation involving further bone debridement, a requirement for the use of long-term suppressive antibiotics or sinus recurrence. Results: Sixty-one adults (mean age 50.2 years, range 16.8-80.6) underwent surgery. According to the Cierny-Mader classification of osteomyelitis there were 19 type II, 35 type III and 7 type IV cases. The ischium was the most common site of infection. Osteomyelitis was usually the result of contiguous focus infection associated with decubitus ulcers, predominantly in patients with spinal or cerebral disorders. Most patients with positive microbiology had polymicrobial infection (52.5%). Thirty patients required soft tissue reconstruction with muscle or myocutaneous flaps. Twelve deaths occurred a mean of 2.8 years following surgery (range 7 days-7.4 years). Excluding these deaths the mean follow-up was 4.6 years (range 1.5-12.2 years). Recurrent infection occurred in seven (11.5%) a mean of 1.5 years post-operatively (92 days - 5.3 years). After further treatment 58 cases (95.1%) were infection free at final follow-up. Interpretation: Patients in this series have many comorbidities and risk factors for poor surgical outcome. Nevertheless, the multidisciplinary approach allows successful treatment in the majority of cases.