A Short-Course Antibiotic Prophylaxis Is Associated with Limited Antibiotic Resistance Emergence in Post-Operative Infection of Pelvic Primary Bone Tumor Resection.

Resections of primary pelvic bone tumors are frequently complicated by surgical site infections (SSIs), thereby impairing the functional prognosis of patients, especially in case of implant removal. Although prophylactic antibiotics play an essential role in preventing SSIs, there are presently no recommendations that support their appropriate use. This study aimed to assess the impact of a 24 h prophylactic protocol on the bacterial ecology, the resistance pattern, and the SSI healing rate. We hypothesized that this protocol not only limits the emergence of resistance but also results in a good cure rate with implant retention in case of SSI. A retrospective study was performed that included all patients with an SSI following a pelvic bone tumoral resection between 2005 and 2017 who received a 24 h antibiotic prophylaxis protocol. Twenty-nine patients with an SSI were included. We observed a 75.9% rate of polymicrobial infection, with a high prevalence of digestive flora microorganisms and a majority of wild-type phenotypes. We confirmed that there was no significant emergence of resistant flora. After first-line debridement, antibiotics (DA) if any implant was used, or debridement, antibiotics, and implant retention (DAIR) whenever possible, we obtained a 79.3% cure rate, with implant removal in 20% of cases. The absence of an implant was significantly associated with SSI healing. Early infection management and low resistance profiles may also have a positive effect, but this needs to be confirmed in a larger cohort. In light of this, the use of a 24 h prophylactic protocol in primary pelvic bone tumor resections is associated with a favorable infection cure rate and implant retention in case of SSI, and minimal selection of resistant microorganisms.

Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection.

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).

IMSYC immunologic synovitis score: A new score for synovial membrane characterization in inflammatory and non-inflammatory arthritis.

OBJECTIVES: Krenn synovitis Score has been developed by Krenn et al. in order to assess synovitis severity and is used in synovial research. Cell signature of synovial tissue can be studied using immunohistochemistry and is of interest as a biomarker for both prognosis and prediction of response to treatment. However, no synovitis score including immunohistochemistry exists yet. In order to answer this unmet need, we propose a new Immunologic Synovitis score (IMSYC) adding 5 components to the Krenn score: CD68, CD3, CD20, CD31 and Ki67 immunostaining. In this study, we aimed to validate this new IMSYC by studying its diagnostic performances in a well-defined collection of synovial samples. METHODS: Synovial samples from patients were obtained during surgical procedures. CD68, CD3, CD20, CD31 and KI67 immunohistochemistry were performed. RESULTS: In total, 77 patients were included. In total, 45 were females, mean age was 63.1 years. Forty had inflammatory arthritis, mainly rheumatoid arthritis (31/40). Non inflammatory arthritis group included 35 patients with mainly osteoarthritis. Mean Krenn score and IMSYC were significantly higher in the inflammatory group (P<0.001). ROC analysis of diagnostic performances determined the score of 13.5 out of 24 as the cut-off that gave the best ratio for discrimination between inflammatory and non-inflammatory arthritis with a sensitivity of 71.8% and specificity of 98%. CONCLUSION: We propose a new synovitis score including immunohistochemistry. This score has a better sensitivity and specificity than the Krenn score and represents a more functional synovitis evaluation. IMSYC could be further used in better categorizing synovial tissue phenotype and give a basis for tissue driven therapy.

Surgical management of lower limb fractures in patients with spinal cord injury less associated with complications than non-operative management: A retrospective series of cases.

OBJECTIVES: To evaluate the difference in terms of overall complications between surgical and non-surgical management of lower limb fractures in patients with chronic spinal cord injury (SCI). DESIGN: A 13-year retrospective study including patients with chronic spinal cord lesion admitted for sublesional lower limb fractures. SETTING: University hospital SCI reference departments (Rehabilitation department and orthopedic department). PARTICIPANTS: Forty patients with SCI were included, 24 men and 16 women. Fifty-six distinct fracture occurrences were responsible for a total of 59 lower limb fractures. We compared the number of overall complications between surgical and non-surgical management of fractures. RESULTS: Non-surgical management was realized for 19 fractures and surgery for 40. Characteristics of operated and non-operated patients at the time of each fracture occurrence did not differ concerning age (P = 0.430), sex (P = 0.890), lesion levels (P = 0.410) and AIS classification (P = 0.790). Data analysis highlighted 20 complications directly due to the fracture site for 16 distinct fractures. Seven medical complications were found in 5 distinct fracture events. Only 10 (25.0%) of 40 surgical managements had at least one medical or post-surgical complication, whereas 12 (63.2%) of 19 non-operative managements had at least one complication. Therefore, the overall rate of complications was significantly higher after non-surgical treatment (P = 0.044). CONCLUSION: Lower extremity fractures due to osteoporosis in patients with SCI are responsible for local and general complications. When possible, surgery may be the best management to propose because of fewer overall complications.

Rifampin-Resistant Cutibacterium (formerly Propionibacterium) namnetense Superinfection after Staphylococcus aureus Bone Infection Treatment.

After rifampin and levofloxacin treatment for a Staphylococcus aureus bone infection, a pyogenic granuloma due to a newly described Cutibacterium species, C. namnetense developed on the tibia former external fixator. This rifampin resistant bacterium, selected during treatment, harbored a mutation in the rpoB gene. This case illustrates the possible in vivo selection of resistant mutant most likely due to the bacterial burden and therefore the importance of adequate bone infection treatment.

Pharmacokinetics of Tedizolid in an Obese Patient after Bariatric Surgery.

An obese woman was treated with oral tedizolid 200 mg once daily for pseudoarthrosis 10 years after Roux-en-Y bypass surgery. Total plasma peak concentration was 2.12 mg/liter 3 h after intake, and area under the concentration-time curve from 0 to 24 h (AUC0-24) was 28.3 mg/liter · h. The AUC0-24/MIC ratio for unbound concentrations and for sensitive Staphylococcus and Streptococcus strains was ≥10.8, higher than the target ratio of 3. These results support the use of tedizolid without adjustment after bariatric surgery.

IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro.

OBJECTIVES: Interleukin (IL)-38 is a newly characterised cytokine that belongs to the IL-1 family. This cytokine is expressed in the rheumatoid arthritis (RA) synovial tissue and IL-38 deficient mice have exacerbated arthritis. Here, we analysed the effect of IL-38 overexpression in the joints of arthritic mice, in human macrophages and synovial fibroblasts in vitro. METHODS: Articular injections of an adeno-associated virus (AAV) 2/8 encoding IL-38 were performed in collagen-induced arthritis (CIA), K/BxN serum transfer-induced arthritis (STIA) and antigen-induced arthritis (AIA) in mice. The effect of IL-38 overexpression was evaluated through clinical scores, immunohistochemistry, microCT, Luminex and RT-qPCR analysis. THP-1 macrophages were transduced with a lentiviral vector to overexpress IL-38. RESULTS: Clinical inflammatory scores were significantly decreased after AAV IL-38 injection in joints of mice with CIA and STIA, but not AIA. This decrease was accompanied by reduced macrophage infiltration and a decreased expression of Th17 cytokines (IL-17, IL-23, IL-22) and TNFα. However, IL-38 overexpression had no effect on cartilage or bone destruction. In vitro, the THP-1 monocytic cell line expressed less IL-6, TNFα and IL-23 after IL-38 overexpression. Conditioned media from these cells, containing released IL-38, also exert an anti-inflammatory effect on human primary macrophages and synovial fibroblasts from patients with RA. CONCLUSIONS: This study shows for the first time that IL-38 overexpression attenuates the severity of experimental arthritis. IL-38 may exert its anti-inflammatory effects by decreasing the production of proinflammatory cytokines by macrophages and synovial fibroblasts. This effect can lead to the development of novel treatment strategies in arthritis.

Failure of combination therapy for Staphylococcus aureus bone infection: a case of in vivo selection with resistance to rifampicin and fusidic acid.

Staphylococcus aureus is one of the main etiologies of bone and device-related infections. Treatment of these orthopedic infections combines mostly rifampicin with other antibiotics. The recurrence or failure rate after fusidic acid/rifampicin treatment remains low (<10%). We discuss here a case of antibiotic treatment failure for Staphylococcus aureus bone infection with in vivo selection of rifampicin and fusidic acid resistance. We also report a new mutation in fusA gene involved in fusidic acid resistance.

Genotypic and phenotypic characterization of Staphylococcus epidermidis causing chronic relapsing prosthetic joint infections.

Twenty-one isolates of Staphylococcus epidermidis from 9 patients with persistent prosthetic joint infections were analysed by pulsed-field gel electrophoresis and antibiotic susceptibility assays. In 7 of these cases, the S. epidermidis isolate was different from that of the initial episode. In 1 further case, the superinfection was polyclonal. Recurrence, i.e., renewed isolation of a clone identical to that of an initial episode, occurred in 3 cases, 1 of which was in the absence of superinfection. A high degree of antibiotic resistance was demonstrated, including methicillin in 17 of 21 strains. In conclusion, a frequent occurrence of superinfection and a high degree of resistance make management of these infections complex.

Improving diagnostic criteria for Propionibacterium acnes osteomyelitis: a retrospective analysis.

The identification of Propionibacterium acnes in cultures of bone and joint samples is always difficult to interpret because of the ubiquity of this microorganism. The aim of this study was to propose a diagnostic strategy to distinguish infections from contaminations. This was a retrospective analysis of all patient charts of those patients with >or=1 deep samples culture-positive for P. acnes. Every criterion was tested for sensitivity, specificity, and positive likelihood ratio, and then the diagnostic probability of combinations of criteria was calculated. Among 65 patients, 52 (80%) were considered truly infected with P. acnes, a diagnosis based on a multidisciplinary process. The most valuable diagnostic criteria were: >or=2 positive deep samples, peri-operative findings (necrosis, hardware loosening, etc.), and >or=2 surgical procedures. However, no single criterion was sufficient to ascertain the diagnosis. The following combinations of criteria had a diagnostic probability of >90%: >or=2 positive cultures + 1 criterion among: peri-operative findings, local signs of infection, >or=2 previous operations, orthopaedic devices; 1 positive culture + 3 criteria among: peri-operative findings, local signs of infection, >or=2 previous surgical operations, orthopaedic devices, inflammatory syndrome. The diagnosis of P. acnes osteomyelitis was greatly improved by combining different criteria, allowing differentiation between infection and contamination.

A case of osteitis due to Staphylococcus aureus and Arcanobacterium bernardiae coinfection.

Arcanobacterium bernardiae human infections remain rare. Only 2 reports are described in the literature. We report on an immunocompetent patient with a long history of chronic osteitis who developed a polymicrobial infection of the knee. The initial isolation of Staphylococcus aureus confounded the diagnosis of A. bernardiae infection, which underlines the need for extended period of incubation and subcultures of enriched liquid culture media. A. bernardiae is a new bacterium implicated in osteoarticular infections.