Are there clinical variables determining antibiotic prophylaxis-susceptible versus resistant infection in open fractures?

Purpose: In Gustilo grade III open fractures, it remains unknown which demographic or clinical features may be associated with an infection resistant to the administered prophylactic agent, compared to one that is susceptible. Methods: This was a retrospective case-control study on patients hospitalized from 2004 to 2009. Results: We identified 310 patients with Gustilo-III open fractures, 36 (12%) of which became infected after a median of tendays. In 26 (72%) of the episodes the pathogen was susceptible to the prophylactic antibiotic agent prescribed upon admission, while in the other ten it was resistant. All antibiotic prophylaxis was intravenous; the median duration of treatment was threedays and the median delay between trauma and surgery was oneday. In multivariate analysis adjusting for case-mix, only Gustilo-grade-IIIc fractures (vascular lesions) showed tendency to be infected with resistant pathogens (odds ratio 10; 95% confidence interval 1.0-10; p = 0.058). There were no significant differences between cases caused by antibiotic resistant and susceptible pathogen cases in patient's sex, presence of immune suppression, duration and choice of antibiotic prophylaxis, choice of surgical technique or materials, time delay until surgery, use of bone reaming, fracture localization, or presence of compartment syndrome. Conclusion: We were unable to identify any specific clinical parameters associated with infection with antibiotic resistant pathogens in Gustilo-grade III open fractures, other than the severity of the fracture itself. More research is needed to identify patients who might benefit from a broader-spectrum antibiotic prophylaxis

Remission rate of implant-related infections following revision surgery after fractures

Purpose: In contrast to a large amount of epidemiological data regarding the incidence of implant infections after fracture management, surprisingly few have been published concerning the success of their treatment. Methods: This was a single-centre cohort study at Geneva University Hospitals from 2000 to 2012 investigating the remission rates of orthopaedic implant infections after fracture repair and associated variables. Results: A total of 139 episodes were included: There were 51 women (37%) and 28 immunosuppressed (20%) patients with a median age and American Society of Anaesthesiologists (ASA) score of 51years and 2 points, respectively. The infected implants were plates (n = 75, 54%), nails (24, 17%), wires (20), screws (10), cerclage cables or wires (3), hip screws (4) or material for spondylodesis (3). A pathogen was identified in 135 (97%) cases, including Staphylococcus aureus (73, 52%), coagulase-negative staphylococci (20), streptococci (7) and 19 Gram-negative rods. All patients underwent antibiotic treatment, and 128 (92%) remained in remission at a median follow-up time of 2.6years (range one to 13years). In multivariate logistic regression analysis, the plate infections were significantly associated with lower remission rates [65/75, 87%, odds ratio (OR) 0.1, 95% confidence interval (CI) 0.01-0.90]. No associations were found for gender, age, immune status, ASA score, additional surgical interventions (OR 0.4, 95% CI 0.1-4.1) or duration of antibiotic treatment (OR 1.0, 95% CI 0.98-1.01). Conclusions: Among all infected and removed orthopaedic implants, plates were associated with slightly lower remission rates, while the overall treatment success exceeded 90%. The duration of antibiotic therapy did not alter the outcom

IGF1 Is a Common Target Gene of Ewing's Sarcoma Fusion Proteins in Mesenchymal Progenitor Cells

The EWS-FLI-1 fusion protein is associated with 85-90% of Ewing's sarcoma family tumors (ESFT), the remaining 10-15% of cases expressing chimeric genes encoding EWS or FUS fused to one of several ets transcription factor family members, including ERG-1, FEV, ETV1 and ETV6. ESFT are dependent on insulin-like growth factor-1 (IGF-1) for growth and survival and recent evidence suggests that mesenchymal progenitor/stem cells constitute a candidate ESFT origin. To address the functional relatedness between ESFT-associated fusion proteins, we compared mouse progenitor cell (MPC) permissiveness for EWS-FLI-1, EWS-ERG and FUS-ERG expression and assessed the corresponding expression profile changes. Whereas all MPC isolates tested could stably express EWS-FLI-1, only some sustained stable EWS-ERG expression and none could express FUS-ERG for more than 3-5 days. Only 14% and 4% of the total number of genes that were respectively induced and repressed in MPCs by the three fusion proteins were shared. However, all three fusion proteins, but neither FLI-1 nor ERG-1 alone, activated the IGF1 promoter and induced IGF1 expression. Whereas expression of different ESFT-associated fusion proteins may require distinct cellular microenvironments and induce transcriptome changes of limited similarity, IGF1 induction may provide one common mechanism for their implication in ESFT pathogenesis

Administration of antibiotic agents before intraoperative sampling in orthopedic infections alters culture results

International audienc

Increased risk of joint failure in hip prostheses infected with Staphylococcus aureus treated with debridement, antibiotics and implant retention compared to Streptococcus

Purpose: The debridement, antibiotic and implant retention (DAIR) procedure is an option for patients with prosthetic hip joint infections for whom arthroplasty removal is problematic. Unfortunately, some of the guidelines proposed for deciding on DAIR management of arthroplasty infections fail to take into consideration the role of the infecting pathogen. While Staphylococcus aureus and streptococci are major contributors to infected hip arthroplasties, their respective contributions to treatment success or failure rates with the DAIR procedure have not been thoroughly analysed from a microbiological perspective. Methods: This retrospective study included all patients who were hospitalised in Geneva University Hospitals between 1996 and 2012 and were initially treated with DAIR for prosthetic hip joint monomicrobial infection due to S. aureus or Streptococcus spp. The outcome of DAIR treatment was evaluated after a minimal follow-up of twoyears. A literature search was also performed to retrieve data from additional DAIR-treated cases in other institutions. Results: In our institution, 38 DAIR-treated patients with hip arthroplasty monomicrobial infections underwent at least one surgical debridement (median two, range one to five), exchange of mobile parts and concomitant targeted antibiotic therapy for several weeks or months. A literature search identified outcome data in other institutions from 52 additional DAIR-treated cases according to our study criteria. After merging our own data with those retrieved from other reports, we found a failure rate of 21 % instead of 24 % for S. aureus-infected, DAIR-treated patients, but no failure in 14 streptococcal-infected patients. In the pooled data, the failure rate linked with S. aureus infections was significantly higher than that with Streptococcus ssp. (19/90 vs 0/14 episodes; Fisher's exact test, P = 0.07). Conclusions: DAIR-treated patients with prosthetic hip joint infections due to S. aureus tended to have worse outcomes than those infected with Streptococcus spp. The specific influence of the infecting pathogen should be considered in future guidelines and recommendations

EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells

Introduction: Cancer stem cells (CSC) display plasticity and self renewal properties reminiscent of normal tissue stem cells but the events responsible for their emergence remain obscure. We have recently identified CSC in Ewing sarcoma family tumors (ESFT) and shown that they arise from mesenchymal stem cells from the bone marrow. Objective of the study: To analyze the mechanisms underlying cancer stem cell development in ESFT. Methods: Primary human mesenchymal stem cells (MSC) isolation from adult and pediatric bone marrow. Retroviral delivery of fusion protein (EWS-FLI1) to primary MSC, and transcriptional and phenotypical analysis. Results: We show that the EWS-FLI-1 fusion gene, associated wit 85-90% of ESFT and believed to initiate their pathogenesis, induces expression of the embryonic stem cell (ESC) genes OCT4, SOX2 and NANOG in human pediatric MSC (hpMSC) but not in their adult counterparts. Moreover, under appropriate culture conditions, hpMSC expressing EWS-FLI-1 generate a cell subpopulation displaying ESFT CSC features in vitro. We further demonstrate that induction of the ESFT CSC phenotype is the result of the combined effect of EWSFLI- 1 on its target gene expression and repression of microRNA-145 (miRNA145) promoter activity. Finally, we provide evidence that EWS-FLI-1 and miRNA-145 function in a mutually repressive feedback loop and identify their common target gene SOX2, in addition to miRNA145 itself, as key players in ESFT cell differentiation and tumorigenicity. Conclusion: Our observations provide insight for the first time into the mechanisms whereby a single oncogene can reprogram primary cells to display a cancer stem cell phenotype

Short parenteral antibiotic treatment for adult septic arthritis after successful drainage

SummaryObjectivesTo assess the risk factors for recurrence of septic arthritis with an emphasis on the duration of antibiotic treatment, to gather data for a prospective study on an optimized antibiotic treatment in adults with septic arthritis.MethodsThis was a retrospective single-center study conducted for the period 1996–2008.ResultsA total of 169 episodes of septic arthritis in 157 adult patients (median age 63 years; 65 females) were included. In 21 episodes (21/169, 12%), arthritis recurred after the end of antibiotic treatment. Multivariate analysis showed that Gram-negative infection (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.4–25.3), immune suppression (OR 5.3, 95% CI 1.3–22.0), and lack of surgical intervention were associated with recurrence. The size of the infected joint, the number of surgical drainages (OR 1.3, 95% CI 1.0–1.7), arthrotomy vs. arthroscopic drainage (OR 0.5, 95% CI 0.2–1.8), duration of antibiotic therapy (OR 1.0, 95% CI 0.95–1.05), and duration of intravenous antibiotic therapy (OR 1.0, 95% CI 1.0–1.0) were not. Seven days of intravenous therapy had the same success rate as 8–21 days (OR 0.4, 95% CI 0.1–1.7) and >21 days (OR 1.1, 95% CI 0.4–3.1). Fourteen days or less of total antibiotic treatment had the same outcome as 15–28 days (OR 0.4, 95% CI 0.1–2.3) or >28 days (OR 0.4, 95% CI 0.1–1.6).ConclusionsIn this retrospective study of adults with septic arthritis, the duration of antibiotic therapy, or an early switch from intravenous to oral administration, did not statistically influence the risk of recurrence. Due to study limitations, the data cannot be used directly for antibiotic therapy recommendations for septic arthritis. Prospective randomized trials are warranted to optimize the antibiotic treatment of septic arthritis