Bacterial DNA enrichment for low-inoculum fracture-related infection diagnostic using high-throughput sequencing.

One of the main barriers for the implementation of metagenomic sequencing in routine diagnosis of infectious diseases is the presence of host DNA. While several enrichment methods are likely to overcome this issue, their effectiveness for specimens such as bone in the case of chronic infections remains to be determined. We compared the relevance of two methods for bacterial DNA enrichment when compared to a reference protocol during pretreatment of bone samples from fracture-related infections before HTS by both Illumina Miseq and Oxford Nanopore Technology (ONT). The bacterial/human DNA ratio was higher for either protocols than the reference technique (p = 0.00012), without any significant difference between them. HTS sensitivity over culture ranged from 21.7 % to 85 %. The ability of the studied protocols to improve the bacterial/human DNA ratio depends on the sequencing technique employed. In this context, there is room for improvement in enhancing the sensitivity of HTS for diagnostic purpose.

Clinical features and treatment outcomes of bone and joint nontuberculous mycobacterial infections according to immune status: a 9-year retrospective observational cohort.

OBJECTIVES: Nontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune status. METHODS: We performed a multicenter retrospective study in France involving patients with documented NTM BJI over a 9-year period. We collected the clinical and microbiological characteristics, management, and clinical outcomes of the patients. RESULTS: Overall, 95 patients were included, of whom 50.5% (48/95) were immunosuppressed. Tenosynovitis was more frequent in the immunocompetent group, and native arthritis more common in the immunosuppressed group. Mycobacerium marinum and M. abscessus complex were significantly more frequent in the immunocompetent group, and M. avium and M. xenopi were significantly more frequent in the immunosuppressed group. The combination of antibiotherapy with surgery tended to be more frequent in the immunocompetent than the immunosuppressed group (63.8% (30/47) vs 47.8% (22/46), respectively); of the latter, 45.7% (21/46) received antimicrobial therapy alone, a higher frequency than in the immunocompetent group (23.4%, 11/47). The median duration of antimicrobial treatment was similar in the two groups (11 months). Mortality was significantly higher in the immunosuppressed group. CONCLUSIONS: Although the clinical presentations and the NTM species involved in BJI differed according to immune status, most recovered completely after treatment.

Correlation between the results of cultures and the molecular BIOFIRE® joint infection panel in a cohort of pediatric patients with bone and joint infections in Bogotá, Colombia.

Introduction: Bone and Joint Infections (BJI) have high morbidity. Methicillin resistant Staphylococcus aureus (MRSA) has increased. Culture-based diagnosis has difficult to recovering fastidious bacteria and detecting polymicrobial infections, molecular methods offer a promising improvement for the diagnosis of BJI with reduced time to result. The aim of the study was to determine the correlation between culture results and the Biofire joint infection panel (BJIP) in a cohort of pediatric patients with BJI. Materials and methods: Descriptive study. Patients admitted with probable o confirmed BJI between July 1, 2019 and February 28, 2021 at HOMI. Blood cultures, synovial and bone fluid samples were taken. Samples were kept at -70 °C. On September 2022, the panel was performed. Results: 32 patients were included. The average age was 83m (RIQ: 32-145). 23 (71.8%) patients had a positive culture. The most frequent microorganism were S. aureus 19 (83%), 11/19 (57.9%) Staphylococci isolates were MRSA. 24/32 (75%) were positive by panel, 20 positive detections were concordant with culture, there were 6 additional isolates by panel (2 S. aureus, 2 S. pyogenes, 1 K. kingae and 1 C. albicans), three microorganisms were isolated in culture but not in the panel. (2 S. aureus and 1 S. agalactiae). Two patients with coinfection were detected. All MRSA were detected by culture and panel. In 26 (81.3%) patients the etiology was documented by any method. Conclusion: These results showed a moderate level of agreement between BJIP and culture (κ = 0.47). The panel allowed the detection of fastidious bacteria including K. kingae and polymicrobial samples. There was a very good level of agreement between the panel and culture for the MRSA detection (κ = 1).

Appropriate Duration of Antimicrobial Treatment for Prosthetic Joint Infections: A Narrative Review.

Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment in this setting, with conflicting results. In this narrative review, we critically appraise the published evidence, considering the different surgical approaches (implant retention [DAIR] and one-step and two-step exchange procedures) separately. In patients managed with DAIR, usually treated for at least 12 weeks, a large, randomized trial failed to show that 6 weeks were non-inferior. However, another randomized clinical trial supports the use of 8 weeks, as long as the surgical conditions are favorable and antibiotics with good antibiofilm activity can be administered. In patients managed with a two-step exchange procedure, usually treated during 6 weeks, a randomized clinical trial showed the efficacy of a 4-week course of antimicrobials. Also, the use of local antibiotics may allow the use of even shorter treatments. Finally, in the case of one-step exchange procedures, there is a trend towards reducing the length of therapy, and the largest randomized clinical trial supports the use of 6 weeks of therapy.

Association of persistent positive blood cultures and infective endocarditis: A cohort study among patients with suspected infective endocarditis.

OBJECTIVES: To ascertain whether infective endocarditis (IE) was associated with persistent bacteraemia/candidaemia among patients with suspected IE. METHODS: This study included bacteraemic/candidaemic adult patients with echocardiography and follow-up blood cultures. Persistent bacteraemia/candidaemia was defined as continued positive blood cultures with the same microorganism for 48 h or more after antibiotic treatment initiation. Each case was classified for IE by the Endocarditis Team. RESULTS: Among 1962 episodes of suspected IE, IE (605; 31%) was the most prevalent infection type. Persistent bacteraemia/candidaemia was observed in 426 (22%) episodes. Persistent bacteraemia was more common among episodes with Staphylococcus aureus bacteraemia compared to episodes with positive blood cultures for other pathogens (32%, 298/933 vs 12%, 128/1029; P < 0.001). Multivariable analysis demonstrated that cardiac predisposing factors (aOR 1.84, 95% CI 1.31-2.60), community or non-nosocomial healthcare-associated (2.85, 2.10-3.88), bacteraemia by high-risk bacteria, such as S. aureus, streptococci, enterococci or HACEK (1.84, 1.31-2.60), two or more positive sets of index blood cultures (6.99, 4.60-10.63), persistent bacteraemia/candidaemia for 48 h from antimicrobial treatment initiation (1.43, 1.05-1.93), embolic events within 48h from antimicrobial treatment initiation (12.81, 9.43-17.41), and immunological phenomena (3.87, 1.09-1.78) were associated with infective endocarditis. CONCLUSIONS: IE was associated with persistent bacteraemia/candidaemia, along with other commonly associated factors.

Assessment of the impact of telehealth intervention in patients with bone and joint infection.

OBJECTIVES: Patients with bone and joint infections (BJI) are involved in a complex care pathway and require prolonged antimicrobial treatment. Some studies have suggested that a pharmacist-led telehealth intervention (TI) could help to ensure better follow-up of chronic diseases. To our knowledge, there are no data on the effects of pharmacist-led TI on patients with BJI. The aim of this study is to assess the impact of a TI on patients treated for BJIs at three weeks after hospital discharge. PATIENTS AND METHODS: Patients encountered during hospitalization and receiving standardized care including TI were included in the study. All adverse events (AE) reported by patients during TI were evaluated. Impact of pharmaceutical interventions (PIs) provided by a clinical pharmacist following TI was evaluated by CLEO© (CLinical, Economic and Organizational) scale. Patient satisfaction concerning TI was assessed by an anonymous questionnaire following medical consultation at the end of antimicrobial treatment. RESULTS: Over a 4-month period, 36 patients received TI. Fifty-two AEs were identified in 21 patients (58%). Two patients were hospitalized due to an AE. Clinical pharmacists provided 34 pharmaceutical interventions (PIs) for 23 patients (64%). According to CLEO scale, 11 PIs had a major clinical impact (32%), 6 PIs (18%) had a favorable impact on the direct cost of treatment and 27 PIs (79%) had positive organizational impact. Concerning TI process, patients were satisfied or very satisfied, with an average score of 9.6/10. CONCLUSION: TI led to a high number of pharmaceutical interventions (PIs), with a meaningful clinical, organizational, and economic impact. Patients were also highly satisfied with this intervention.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome secondary to antimicrobial therapy in pediatric bone and joint infections.

Background: Bone and joint infections are common in children, particularly those under 10 years of age. While antimicrobial therapy can often successfully treat these infections, surgical drainage may also be necessary. It is important to note that prolonged courses of treatment have been associated with adverse events and drug reactions. Among these, drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome is particularly severe and potentially life-threatening. We aimed to evaluate the cases of DRESS syndrome that develop during the treatment of bone and joint infections. Methods: A retrospective study was conducted at a tertiary-level university hospital between 2015 and 2022 to determine the incidence and outcomes of definite DRESS Syndrome in children under 18 years of age with bone and joint infections. Results: Of 73 patients with bone and joint infections, 16 (21.9 %) children developed antimicrobial therapy-induced DRESS syndrome. Eight (50 %) of these children were boys; the mean age of the patients was 9.76 ± 5.5 years. DRESS syndrome occurred in 16 children, including 13 children with osteomyelitis, 1 child with osteomyelitis and septic arthritis, and 2 children with septic arthritis and sacroiliitis. The mean duration of intravenous antibiotic therapy was 40.6 ± 16.6 days; the mean hospital stay was 48.7 ± 23.7 days; the mean time for the development of DRESS syndrome after starting antibiotics was 19.6 ± 7.68 days. New onset fever (68.8 %) and rash (43.8 %) were the most common symptoms of DRESS Syndrome. Cefotaxime and vancomycin were drugs responsible for DRESS syndrome in 8 (50 %) of 16. The causative antibiotics were switched to another class of antibiotic, most commonly preferred was ciprofloxacin (n:5; 31.3 %). For children with persistent symptoms, steroids were used in 5 (31.25) patients. Conclusions: Clinicians should be aware of DRESS syndrome in children who develop fever and rash under long-term antibiotics and should check hematological and biochemical parameters to predict the severity of DRESS syndrome. In patients with persistent symptoms, steroids may be used to control the symptoms.

Imaging in osteoarticular infection in adults.

BACKGROUND: Osteoarticular infections are uncommon and required a multimodal approach for diagnosis. Imaging forms an important component of this multimodal approach. OBJECTIVES: In this narrative review, we describe the different imaging modalities, features of osteoarticular infections present on these imaging approaches and recommendations for which imaging modality should be considered in different types of osteoarticular infections. SOURCES: This narrative review was based on literature review from PubMed and was limited to bacterial infections in adult patients. CONTENT: Imaging modalities include modalities that provide information on the anatomy or radionuclide imaging that provides information about the metabolic activity of the area of interest. Anatomical imaging includes plain radiographs (X-ray), computed tomography, and magnetic resonance imaging. Radionuclide approaches include three-phase bone scintigraphy, gallium scans, white blood cell scintigraphy, and 18F-fluorodeoxy-glucose positron emission tomography. The optimal radiological modality for diagnosis is influenced by multiple factors, including infection location, presence of metalware, timing of infection from any preceding surgery or fracture, antibiotic use, and patient comorbidities. Local availability of scanning modality, tracer supply, technical expertise, and patient access also influences choice. IMPLICATIONS: A collaborative approach with imaging, pathology and clinical input in a multidisciplinary setting is paramount for the diagnosis of osteoarticular infections. Increasing research and improvements in technology will further improve the utility and accuracy of imaging approaches for imaging in osteoarticular infections.

Clinical and molecular characteristics of methicillin-resistant Staphylococcus aureus in bone and joint infection among children.

OBJECTIVE: To investigate the characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) in bone and joint infection (BJI) among children. METHODS: A total of 338 patients diagnosed with BJI from 2013 to 2022 in Children's Hospital of Fudan University were enrolled. Demographic information, microbiology culture results and laboratory findings, including white blood counts (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and erythrocyte sedimentation rate (ESR) were collected and analyzed. MRSA was confirmed by antimicrobial susceptibility testing. Other MRSA-caused infections were randomly selected for comparison. Twenty-three virulence and antimicrobial resistance (AMR) genes were screened for MRSA strains. Multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing were performed using PCR amplification and sequencing. RESULTS: Of the identified pathogens in BJI, MRSA accounted for 21.0% (47/224). Patients with BJI had high levels of initial CRP, white blood cell count (WBC) and IL-6. ST59 (43.9%) and t437 (37.6%) were the main MRSA subtypes isolated from the children. The major genotypes in BJI were ST59-t437 (29.8%) and ST22-t309 (14.9%), with high carriage of hemolysins including hla (94.4-100%), hlb (66.2-93.3%), and hld (100%). Notably, Panton-Valentine leukocidin (pvl) had a high prevalence (53.3%) in ST22-t309-MRSA. Other virulence genes including tst, seg and sei were more commonly detected in ST22-t309-MRSA (40.0-46.7%) than in ST59-t437-MRSA (4.2-9.9%). High-carriage AMR genes in MRSA included aph(3')/III (66.7-80%), ermB (57.5-73.3%) and ermC (66.7-78.9%). MRSA presented high-resistance to erythromycin (52.0-100%) and clindamycin (48.0-92.5%), different genotypes displayed variation in their susceptibilities to antibiotics. CONCLUSIONS: The major MRSA genotype in BJI was ST59-t437, followed by ST22-t309, with a higher prevalence of the pvl gene. Continuous surveillance of pvl-positive ST22-t309-MRSA in pediatric BJI infections is thus required.

Safety and tolerability of tedizolid as oral treatment for bone and joint infections.

Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxazolidinone, linezolid. However, there are limited prospective safety data. We conducted an open-label, non-comparative trial of oral tedizolid for BJI treatment. Primary outcomes were safety and cure rate. Eligible patients had a BJI caused by documented or suspected Gram-positive pathogen, required 4-12 weeks of therapy, and did not have myelosuppression or peripheral/optic neuropathy. Subjects underwent weekly evaluation for cytopenias and neuropathy. We enrolled 44 subjects; five were lost to follow-up. Two subjects did not complete planned treatment because of rash (n = 1) and urgent surgery (n = 1). Of 37 patients with evaluable outcomes, 17 (46%) had hardware-associated infection, 13 (35%) had osteomyelitis, 5 (14%) had prosthetic joint infection, and 2 (5%) had other BJIs. Median (mean, range) treatment duration was 12 (10.1, 4-12) weeks. There were no cases of cytopenias or peripheral or optic neuropathy. Treatment cure occurred in 13 (35%); 19 (51%) required antibiotic continuation after 12 weeks of tedizolid related to retained hardware at the BJI site, and failure occurred in four (11%), two unlikely, one possibly, and one probably due to tedizolid. We found that oral tedizolid was well tolerated for prolonged BJI treatment without significant toxicity. Clinical failure rate was similar to that of other published BJI investigations. (This study has been registered at Clinicaltrials.gov under identifier NCT03009045.) IMPORTANCE Bone and joint infections are common infections with limited effective and safe oral options for Gram-positive infections. The largest prospective clinical trial of tedizolid therapy for bone and joint infections enrolled 44 patients and tested each in person weekly with detailed safety monitoring including tests for leukopenia, anemia, thrombocytopenia, peripheral neuropathy, and optic neuropathy for up to 12 weeks. Findings demonstrated tedizolid was generally well tolerated and there were no incident cases of cytopenias or neuropathy. Cure rates were similar to that in other bone and joint infection studies. In summary, oral tedizolid appears to be a well-tolerated oral option for Gram-positive bone and joint infections.

Carbapenem-Resistant Pseudomonas aeruginosa Spondylodiscitis Treated with Ceftazidime-Avibactam: A Case Report with Literature Review.

Pyogenic spondylodiscitis (PS) is a highly morbid and potentially fatal bacterial infection with an increasing incidence in recent decades. Its diagnosis and treatment are challenging, especially with the expansion of multidrug- or extensively drug-resistant bacteria. We report a rare case of PS caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) that was treated with ceftazidime-avibactam (C/A). The choice of C/A therapy was based on the patient's bacterial sensitivity profile and intolerance to the initial therapeutic regimen (polymyxin B and meropenem). The total antimicrobial treatment time was seven weeks. The evolution of the clinical course met the cure criteria, which was characterized by remission of signs and symptoms, normalization of inflammatory markers, and radiological improvement over 18 months of clinical follow-up. This is a rare case of CRPA spondylodiscitis that responded to C/A treatment.

Pharmacokinetic interaction between rifampicin and clindamycin in staphylococcal osteoarticular infections.

OBJECTIVES: Oral combination of clindamycin and rifampicin is relevant for the treatment of staphylococcal osteoarticular infection (SOAIs). However, rifampicin induces CYP3A4, suggesting a pharmacokinetic interaction with clindamycin with unknown pharmacokinetic/pharmacodynamic (PK/PD) consequences. This study aimed to quantify clindamycin PK/PD markers before and during rifampicin co-administration in SOAI. METHODS: Patients with SOAI were included. After initial intravenous antistaphylococcal treatment, oral therapy was started with clindamycin (600 or 750 mg t.i.d.), followed by addition of rifampicin 36 h later. Population PK analysis was performed using the SAEM algorithm. PK/PD markers were compared with and without rifampicin co-administration, each patient being his own control. RESULTS: In 19 patients, clindamycin median (range) trough concentrations were 2.7 (0.3-8.9) mg/L and <0.05 (<0.05-0.3) mg/L before and during rifampicin administration, respectively. Rifampicin co-administration increased clindamycin clearance by a factor 16 and reduced the AUC0-8h/MIC by a factor 15 (P < 0.005). Clindamycin plasma concentrations were simulated for 1000 individuals, without and with rifampicin. Against a susceptible Staphylococcus aureus strain (clindamycin MIC 0.0625 mg/L), >80% of individuals would reach all proposed PK/PD targets without co-administration of rifampicin, even with low clindamycin dose. For the same strain, when rifampicin was co-administered, the probability to reach clindamycin PK/PD targets dropped to 1% for %fT>MIC = 100% and to 6% for AUC0-24h/MIC > 60, even with high clindamycin dose. CONCLUSION: Rifampicin co-administration with clindamycin has a high impact on clindamycin exposure and PK/PD targets in SOAI, which could result in clinical failure even for fully susceptible strains.

Partial-Oral Antibiotic Therapy for Bone and Joint Infections in People With Recent Injection Drug Use.

Background: Limited outcome data exist regarding partial-oral antibiotic therapy, defined as oral antibiotics as part of a patient's treatment, for bone and joint infections (BJIs) in people who inject drugs (PWID). Methods: We conducted a retrospective study of all PWID reporting drug use within 3 months and BJIs requiring ≥6 weeks of antibiotics in an urban safety-net hospital between February 1, 2019, and February 1, 2021. Treatment outcomes were assessed by chart review. Rates of failure, defined as death, symptoms, or signs concerning for worsening or recurrent infections, were assessed 90 and 180 days after completion of antibiotics. Univariate logistic regression was used to explore the association between covariates and failure. Results: Of 705 patients with BJI, 88 (13%) were PWID. Eighty-six patients were included in the final cohort. Forty-four (51%) were homeless, 50 (58%) had spine infection, 68 (79%) had surgery, and 32 of 68 (47%) had postoperatively retained hardware. Twelve (14%) of 86 patients received exclusively intravenous (IV) antibiotics, and 74 (86%) received partial-oral antibiotics. Twelve (14%) of 86 patients had patient-directed discharge. In those who received partial-oral antibiotics, the failure rate was 20% at 90 days and 21% at 180 days after completion of intended treatment. Discharge to a medical respite and follow-up with infectious diseases (ID) or surgery were negatively associated with odds of failure. Conclusions: Partial-oral treatment of BJI in PWID was a common practice and often successful when paired with medical respite and follow-up with ID or surgery.

2022 SPILF - Clinical Practice guidelines for the diagnosis and treatment of disco-vertebral infection in adults.

These guidelines are an update of those made in 2007 at the request of the French Society of Infectious Diseases (SPILF, Société de Pathologie Infectieuse de Langue Française). They are intended for use by all healthcare professionals caring for patients with disco-vertebral infection (DVI) on spine, whether native or instrumented. They include evidence and opinion-based recommendations for the diagnosis and management of patients with DVI. ESR, PCT and scintigraphy, antibiotic therapy without microorganism identification (except for emergency situations), therapy longer than 6 weeks if the DVI is not complicated, contraindication for spinal osteosynthesis in a septic context, and prolonged dorsal decubitus are no longer to be done in DVI management. MRI study must include exploration of the entire spine with at least 2 orthogonal planes for the affected level(s). Several disco-vertebral samples must be performed if blood cultures are negative. Short, adapted treatment and directly oral antibiotherapy or early switch from intravenous to oral antibiotherapy are recommended. Consultation of a spine specialist should be requested to evaluate spinal stability. Early lifting of patients is recommended.

Molecular Tools for Guiding Therapy in Patients With Staphylococcal Bone and Joint Infections: A Diagnostic Test Accuracy Meta-analysis.

Background: Timely detection of causative pathogens and their antimicrobial resistance are essential for guiding targeted therapies in bone and joint infections (BJI) patients. We performed a systematic review and meta-analysis to assess the diagnostic value of testing osteoarticular samples with the nucleic acid amplification tests (NAAT) for effective staphylococcal strain identification and the administration of appropriately targeted antimicrobial agents in BJI patients. Methods: Five databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library, were searched for related publications from inception to July 24, 2021. Studies comparing the diagnostic accuracy of NAAT to a microbiological culture reference standard of osteoarticular specimens were eligible. Pooled summary values of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of NAAT compared to the microbiological culture reference standard were calculated using bivariate random-effects meta-analyses. Results: From 906 citations, 11 studies were included. Eleven studies comprising 13 datasets (n = 1047) evaluated NAAT accuracy for methicillin-sensitive Staphylococcus aureus (MSSA) identification, while seven studies comprising nine datasets (n = 727) evaluated methicillin-resistant Staphylococcus aureus (MRSA) identification. Against the microbiological culture reference standard, the pooled summary estimates for detection of both MSSA [sensitivity: 0.89 (95% confidence interval [CI] 0.84-0.93), specificity: 0.99 (95% CI 0.97-0.99), PLR: 34.13 (95% CI 20.54-56.73), NLR: 0.19 (95% CI 0.12-0.3), and DOR: 283.37 (95% CI 129.49-620.1)] and MRSA [sensitivity: 0.81 (95% CI 0.67-0.91), specificity: 1.0 (95% CI 0.99-1.0), PLR: 62.1 (95% CI 24.5-157.6), NLR: 0.33 (95% CI 0.16-0.69), and DOR: 300.25 (95% CI 85.01-1060.5)] were comparable. Heterogeneity was moderate. GeneXpert was frequently used among NAA tests, and its diagnostic accuracy was in line with the overall pooled summary estimates. The heterogeneity in diagnostic efficacy (P >0.05) could not be explained by a meta-regression and subgroup analysis of the research design, sample condition, and patient selection technique. Conclusions: Our study suggested that NAAT can be applied as the preferred prescreening test for the timely diagnosis of staphylococcal strains associated with BJI in osteoarticular samples for successful antimicrobial therapy.

Epidemiology and outcomes of bone and joint infections in solid organ transplant recipients.

Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008-31.12.2019) were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p < .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future.

Excellent Outcomes With the Selective Use of Oral Antibiotic Therapy for Bone and Joint Infections: A Single-Center Experience.

Background and objective Recent studies have challenged the notion that prolonged intravenous (IV) antibiotics are preferable to oral antibiotics for treating musculoskeletal infections. Our institution's orthopedic surgery and orthopedic infectious disease (ID) groups have established consensus criteria for the use of oral antibiotics in musculoskeletal infections. In this study, we examine one-year and two-year outcomes of the selective use of oral antibiotics for musculoskeletal infections in a real-world setting. Methods We conducted a single-center retrospective analysis of adults seen in our orthopedic ID clinic over a six-month period for the first episode of surgically managed osteomyelitis, native joint septic arthritis (NJSA), prosthetic joint infection (PJI), or other musculoskeletal hardware infection with an established microbiologic etiology who received surgical interventions and >2 weeks of antimicrobial treatment. Patients were evaluated for treatment failure at one year and two years following their index surgery, which we defined as death, unplanned surgery, or the initiation of chronic antibiotic suppression. Results One-year treatment failure rates were 0/23 (0%) in patients who switched to oral therapy versus 6/17 (35%) in patients who remained on IV treatment. Two-year treatment failure rates were 0/23 (0%) in patients who switched to oral therapy versus 8/17 (47%) in patients who remained on IV treatment. Conclusions Our consensus criteria for the switch to oral antibiotics for musculoskeletal infections identified patients who went on to have excellent outcomes at one year and two years, suggesting that these criteria can effectively identify patients at low risk for treatment failure. Collaboration between ID specialists and orthopedic surgeons to select antimicrobial regimens can avoid significant burdens, costs, and complications associated with prolonged IV therapy.

The DendrisCHIP® Technology as a New, Rapid and Reliable Molecular Method for the Diagnosis of Osteoarticular Infections.

Osteoarticular infections are major disabling diseases that can occur after orthopedic implant surgery in patients. The management of these infections is very complex and painful, requiring surgical intervention in combination with long-term antibiotic treatment. Therefore, early and accurate diagnosis of the causal pathogens is essential before formulating chemotherapeutic regimens. Although culture-based microbiology remains the most common diagnosis of osteoarticular infections, its regular failure to identify the causative pathogen as well as its long-term modus operandi motivates the development of rapid, accurate, and sufficiently comprehensive bacterial species-specific diagnostics that must be easy to use by routine clinical laboratories. Based on these criteria, we reported on the feasibility of our DendrisCHIP® technology using DendrisCHIP®OA as an innovative molecular diagnostic method to diagnose pathogen bacteria implicated in osteoarticular infections. This technology is based on the principle of microarrays in which the hybridization signals between oligoprobes and complementary labeled DNA fragments from isolates queries a database of hybridization signatures corresponding to a list of pre-established bacteria implicated in osteoarticular infections by a decision algorithm based on machine learning methods. In this way, this technology combines the advantages of a PCR-based method and next-generation sequencing (NGS) while reducing the limitations and constraints of the two latter technologies. On the one hand, DendrisCHIP®OA is more comprehensive than multiplex PCR tests as it is able to detect many more germs on a single sample. On the other hand, this method is not affected by the large number of nonclinically relevant bacteria or false positives that characterize NGS, as our DendrisCHIP®OA has been designed to date to target only a subset of 20 bacteria potentially responsible for osteoarticular infections. DendrisCHIP®OA has been compared with microbial culture on more than 300 isolates and a 40% discrepancy between the two methods was found, which could be due in part but not solely to the absence or poor identification of germs detected by microbial culture. We also demonstrated the reliability of our technology in correctly identifying bacteria in isolates by showing a convergence (i.e., same bacteria identified) with NGS superior to 55% while this convergence was only 32% between NGS and microbial culture data. Finally, we showed that our technology can provide a diagnostic result in less than one day (technically, 5 h), which is comparatively faster and less labor intensive than microbial cultures and NGS.

Enhancing Diagnostics in Orthopedic Infections.

Accurate diagnosis of orthopedic infection is crucial in guiding both antimicrobial therapy and surgical management in order to optimize patient outcomes. A variety of microbiological and nonmicrobiological methods are used to establish the presence of a musculoskeletal infection. In this minireview, we examine traditional culture-based and newer molecular methodologies for pathogen detection, as well as systemic and localized assays to assess host response to maximize diagnostic yield.

A nomogram for decision-making assistance on surgical treatment of chronic osteomyelitis in long bones: Establishment and validation based on a retrospective multicenter cohort.

BACKGROUND: Chronic osteomyelitis remains a major challenge for orthopedic surgeons due to its high recurrence rate. Surgeons currently have few tools to estimate the likelihood of individual recurrence. We here aimed to develop a nomogram to better estimate individual recurrence rate after surgical treatment of chronic osteomyelitis in long bones. METHODS: We first retrospectively identified patients as training cohort who had received surgical treatment of chronic osteomyelitis in long bones between January 2010 and January 2016 from four hospitals. Patient demographic, microbiological, clinical, and therapeutic variables were collected and analyzed. Univariate and multivariate analyses were performed successively to identify independently predictive factors for recurrence. To reduce overfitting, the Bayesian information criterion was used to reduce variables in the original model. Nomograms were created with the reduced model after model selection. The nomogram was then internally validated with bootstrap resampling. We then further validated the performance of the established nomogram in validation cohort (data from two distinct institutions). RESULTS: Recurrence was found in 136 of 655 (20.8%) and 52 of 201 patients (25.9%) in training and validation cohorts respectively. We included six independent prognostic factors for recurrence in our prediction model: number of previous recurrences, epiphysial involvement, preoperative serum albumin level, axial length of the infectious lesion, lesion-removal method, and application of a muscular flap. After incorporating these six factors, the nomogram achieved good discrimination, with concordance indexes of 0.82 (95% CI, 0.79-0.85) and 0.80 (95% CI, 0.78-0.83) in predicting recurrence in the training and validation cohorts, respectively. Calibration curves were well fitted for both training and validation cohorts. CONCLUSIONS: Our nomogram achieved good preoperative prediction of recurrence in chronic osteomyelitis of long bones. Using this nomogram, the recurrence risk can be confidently predicted for each patient and treatment plan. After considering and discussing the functional prognosis with patients, physicians can establish a rational therapeutic plan. LEVEL OF EVIDENCE: Prognostic, Level III.