Transverse Myelitis Following SARS-CoV-2 Vaccination: A Pharmacoepidemiological Study in the World Health Organization's Database.

BACKGROUND: Transverse myelitis (TM) has recently been associated by health authorities with Ad26.COV2.S (Janssen/Johnson & Johnson), one of the 5 US Food and Drug Administration (FDA) or European Medicines Agency (EMA) labeled severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. It is unknown whether a similar association exists for the other FDA or EMA labeled SARS-CoV-2 vaccines (BNT162b2 [Pfizer/BioNTech], mRNA-1273 [Moderna], ChAdOx1nCov-19 [Oxford-AstraZeneca], and NVX-CoV2373 [Novavax]). This study aimed to evaluate the association between SARS-CoV-2 vaccine class and TM. METHODS: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from VigiBase, the World Health Organization's pharmacovigilance database. We first conducted a disproportionality analysis with the information component (IC) using the reports of TM that occurred within 28 days following exposure to the FDA or EMA labeled SARS-CoV-2 vaccines, from December 1, 2020 (first adverse event related to a SARS-CoV-2 vaccine) to March 27, 2022. Second, we analyzed the clinical features of SARS-CoV-2 vaccine-associated TM cases reported in VigiBase. RESULTS: TM was significantly associated both with the messenger ribonucleic acid (mRNA)-based (n = 364; IC025  = 0.62) and vector-based (n = 136; IC025  = 0.52) SARS-CoV-2 vaccines that are authorized by the FDA or the EMA. CONCLUSIONS: Findings from this observational, cross-sectional pharmacovigilance study showed that mRNA-based and vector-based FDA/EMA labeled SARS-CoV-2 vaccines can be associated with TM. However, because TM remains a rare event, with a previously reported rate of 0.28 cases per 1 million vaccine doses, the risk-benefit ratio in favor of vaccination against SARS-CoV-2 virus remains unchallenged. Rather, this study suggests that clinicians should consider the diagnosis of TM in patients presenting with early signs of spinal cord dysfunction after SARS-CoV-2 vaccination. ANN NEUROL 2022;92:1080-1089.

Association between road traffic accidents and drugs belonging to the antiseizure medications class: A pharmacovigilance analysis in VigiBase.

AIMS: Due to their central mechanism of action, antiseizure medications (ASMs) could lead to adverse effects likely to impair driving skills. Their extended use to neuropsychiatric disorders makes it a class of drugs to monitor for their road traffic accidental (RTA) potential. We aimed to assess the reporting association between ASMs and RTAs using the World Health Organization pharmacovigilance database (VigiBase). METHODS: We performed a disproportionality analysis to compute adjusted reporting odds ratios to evaluate the strength of reporting association between ASMs and RTAs. A univariate analysis using the reporting odds-ratio was used to assess drug-drug interactions between ASMs and RTAs. RESULTS: There were 1 341 509 reports associated with at least 1 ASM in VigiBase of whom 2.91‰ were RTAs reports. Eight ASMs were associated with higher reporting of RTAs compared to others (ranging from 1.35 [95% confidence interval 1.11-1.64] for lamotrigine to 4.36 [95% confidence interval 3.56-5.32] for cannabis). Eight significant drug-drug interactions were found between ASMs and the onset of RTA, mainly involving CYP450 induction. CONCLUSION: A significant safety signal between RTAs and some ASMs was identified. Association of several ASMs might further increase the occurrence of RTA. ASMs prescription in patients with identified risk factors of RTA should be considered with caution. Study number: ClinicalTrials.gov, NCT04480996.

Conservative surgical treatment for metatarsal osteomyelitis in diabetic foot: experience of two French centres.

AIMS: Conservative surgery (CS) for diabetic foot osteomyelitis (DFO) consists in removing all or part of the infected bone tissues without amputation, in complement with antibiotic therapy. Data on CS for DFO therapy are scarce. MATERIAL AND METHODS: We performed a retrospective analysis of all DFO episodes treated with CS between 06/2007 and 12/2017. Remission was defined by the absence of soft-tissue infection, complete sustained (i.e. > 1 month) healing of the foot ulcer, favourable (i.e., stabilisation or improvement) radiological outcome, and no need for additional surgery during a 1-year follow-up. RESULTS: During the study period, 47 episodes (in 41 patients) were analysed. Excluding deaths (all unrelated to the DFO; n = 3) or loss to follow-up before 1 year (n = 5), the remission rate was 64.2%. Most failures occurred during the first 6 months (79%, 11/14). Patients who experienced failure had a higher rate of peripheral arterial disease with arterial stenosis than patients in remission (57% vs. 24%, P = 0.03), a higher C-reactive protein rate at admission (116 ± 112 mg/L vs. 48 ± 46 mg/L, P = 0.02), and a trend for a higher rate of abscesses (29% vs. 4%, P = 0.06). At 1-year follow-up, foot ulcers related to transfer lesion were identified in 25.5% of the cases. At the last follow-up (mean 3 ± 2 years), the remission rate was 23/25 (92%). CONCLUSIONS: Our results suggest that CS is a therapeutic option in patients with localised but severe DFO. Clinicians should, however, consider the necessity of revascularisation, and higher risk of failure if surgery is performed in patients presenting with acute foot infections.

Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study.

Purpose: The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date. Methods: A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period. Results: Patients ( n = 57 ) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli ( n = 16 ), Pseudomonas aeruginosa ( n = 14 ; XDR 50 %), Klebsiella spp. ( n = 7 ), Enterobacter spp. ( n = 9 ), Acinetobacter spp. ( n = 5 ), Proteus mirabilis ( n = 3 ), Serratia marcescens ( n = 2 ) and Stenotrophomonas maltophilia ( n = 1 ). The prevalence of ESBL (extended-spectrum ß -lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients ( n = 37 ; 64.9 %) were treated with a combination including carbapenems ( n = 32 ) and colistin ( n = 11 ) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) ( p = 0.008 ). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age > 60  years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540-9.752; p = 0.004 ) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144-6.963; p = 0.024 ). Conclusions: Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.

Relative contribution of three main virulence factors in Pseudomonas aeruginosa pneumonia.

OBJECTIVE: The pathogenesis and the outcome of Pseudomonas aeruginosa ventilator-acquired pneumonia depend on the virulence factors displayed by the bacteria as well as the host response. Thus, quorum sensing, lipopolysaccharide, and type 3 secretion system have each individually been shown to be important virulence systems in laboratory reference strains. However, the relative contribution of these three factors to the in vivo pathogenicity of clinically relevant strains has never been studied. We analyzed the virulence of 56 nonclonal Pseudomonas aeruginosa strains isolated from critically ill patients with ventilator-acquired pneumonia. To avoid the variation of human immune response, we used a murine model of pneumonia. The aim was to determine which virulence factor was the most important. SETTING: Research laboratory of a university. SUBJECTS: Male adult BALB/c mice. INTERVENTIONS: In vitro, the phenotype of each strain was established as to the expression of quorum sensing-regulated factors (elastase and pyocyanin), type 3 secretion system exotoxin secretion (Exotoxin U, S and/or T, or "nonsecreting"), and lipopolysaccharide O-antigen serotype. Strain pathogenicity was evaluated in vivo in a mouse model of acute pneumonia through lung injury assessment by measuring alveolar-capillary barrier permeability to proteins, lung wet/dry weight ratio, and bacterial dissemination. Associations were then sought between virulence system phenotypes and levels of lung injury. MEASUREMENTS AND MAIN RESULTS: In univariate analysis, elastase production, O11 serotype, and type 3 secretion system exotoxin secretion were associated with increased lung injury and exotoxin U was linked to an increase risk of bacteremia. In multivariate analysis, we observed that type 3 secretion system exotoxin secretion and to a lesser degree elastase production were associated with increased lung injury. CONCLUSION: In a murine model of pneumonia, our data suggest that type 3 secretion system and elastase are the most important virulence factors in clinically relevant P. aeruginosa strains.

Effect of Professional and Extra-Professional Exposure on Seroprevalence of SARS-CoV-2 Infection among Healthcare Workers of the French Alps: A Multicentric Cross-Sectional Study.

We aimed to report SARS-CoV-2 seroprevalence after the first wave of the pandemic among healthcare workers, and to explore factors associated with an increased infection rate. We conducted a multicentric cross-sectional survey from 27 June to 31 September 2020. For this survey, we enrolled 3454 voluntary healthcare workers across four participating hospitals, of which 83.4% were female, with a median age of 40.6 years old (31.8-50.3). We serologically screened the employees for SARS-CoV-2, estimated the prevalence of infection, and conducted binomial logistic regression with random effect on participating hospitals to investigate associations. We estimated the prevalence of SARS-CoV-2 infection at 5.0% (95 CI, 4.3%-5.8%). We found the lowest prevalence in health professional management support (4.3%) staff. Infections were more frequent in young professionals below 30 years old (aOR = 1.59, (95 CI, 1.06-2.37)), including paramedical students and residents (aOR = 3.38, (95 CI, 1.62-7.05)). In this group, SARS-CoV-2 prevalence was up 16.9%. The location of work and patient-facing role were not associated with increased infections. Employees reporting contacts with COVID-19 patients without adequate protective equipment had a higher rate of infection (aOR = 1.66, (95 CI, 1.12-2.44)). Aerosol-generating tasks were associated with a ~1.7-fold rate of infection, regardless of the uptake of FFP2. Those exposed to clusters of infected colleagues (aOR = 1.77, (95 CI, 1.24-2.53)) or intra-familial COVID-19 relatives (aOR = 2.09, (95 CI, 1.15-3.80)) also had a higher likelihood of infection. This report highlights that a sustained availability of personal protective equipment limits the SARS-CoV-2 infection rate to what is measured in the general population. It also pinpoints the need for dedicated hygiene training among young professionals, justifies the systematic eviction of infected personnel, and stresses the need for interventions to increase vaccination coverage among any healthcare workers.

FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells.

Ubiquitination by serving as a major degradation signal of proteins, but also by controlling protein functioning and localization, plays critical roles in most key cellular processes. Here, we show that MITF, the master transcription factor in melanocytes, controls ubiquitination in melanoma cells. We identified FBXO32, a component of the SCF E3 ligase complex as a new MITF target gene. FBXO32 favors melanoma cell migration, proliferation, and tumor development in vivo. Transcriptomic analysis shows that FBXO32 knockdown induces a global change in melanoma gene expression profile. These include the inhibition of CDK6 in agreement with an inhibition of cell proliferation and invasion upon FBXO32 silencing. Furthermore, proteomic analysis identifies SMARC4, a component of the chromatin remodeling complexes BAF/PBAF, as a FBXO32 partner. FBXO32 and SMARCA4 co-localize at loci regulated by FBXO32, such as CDK6 suggesting that FBXO32 controls transcription through the regulation of chromatin remodeling complex activity. FBXO32 and SMARCA4 are the components of a molecular cascade, linking MITF to epigenetics, in melanoma cells.

Tolerability of prolonged linezolid therapy in bone and joint infection: protective effect of rifampicin on the occurrence of anaemia?

BACKGROUND: Linezolid therapy has shown high rates of clinical success in patients with osteomyelitis and prosthetic joint infections caused by Gram-positive cocci. Recent studies have demonstrated that linezolid/rifampicin combination therapy prevents the emergence of rifampicin-resistant mutations in vitro. However, linezolid/rifampicin combination-related haematological and neurological toxicities have not been evaluated. OBJECTIVES: To assess the tolerability of prolonged linezolid/rifampicin combination therapy compared with other linezolid-containing regimens in patients with bone and joint infections. METHODS: We reviewed the medical records of 94 patients who had received linezolid for >4 weeks after bone and joint infections. Anaemia was defined as a ≥2 g/dL reduction in haemoglobin, leucopenia as a total leucocyte count <4 × 10(9)/L, and thrombocytopenia as a reduction in platelet count to <75% of baseline. RESULTS: Anaemia was less frequent among patients on linezolid/rifampicin combination therapy than among patients on linezolid alone or in combination with other drugs (9.3%, 44% and 52%, respectively; P<0.01). In multivariate analysis, age and treatment group were independently associated with anaemia. Thrombocytopenia was reported in 44% of patients on linezolid/rifampicin combination therapy, in 48% of patients on linezolid alone and in 57.7% of patients on other linezolid-containing regimens. Age was the only variable associated with thrombocytopenia (P=0.019) in univariate analysis. CONCLUSIONS: Linezolid/rifampicin combination therapy was associated with a significantly reduced incidence of anaemia among patients with bone and joint infections, but it did not have an effect on thrombocytopenia and peripheral neuropathy rates. Linezolid/rifampicin combination therapy was not associated with poor clinical outcomes.

TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors.

cMet is a well-characterized oncogene that is the target of many drugs including small molecule and biologic pathway inhibitors, and, more recently, antibody-drug conjugates (ADCs). However, the clinical benefit from cMet-targeted therapy has been limited. We developed a novel cMet-targeted 'third-generation' ADC, TR1801-ADC, that was optimized at different levels including specificity, stability, toxin-linker, conjugation site, and in vivo efficacy. Our nonagonistic cMet antibody was site-specifically conjugated to the pyrrolobenzodiazepine (PBD) toxin-linker tesirine and has picomolar activity in cancer cell lines derived from different solid tumors including lung, colorectal, and gastric cancers. The potency of our cMet ADC is independent of MET gene copy number, and its antitumor activity was high not only in high cMet-expressing cell lines but also in medium-to-low cMet cell lines (40 000-90 000 cMet/cell) in which a cMet ADC with tubulin inhibitor payload was considerably less potent. In vivo xenografts with low-medium cMet expression were also very responsive to TR1801-ADC at a single dose, while a cMet ADC using a tubulin inhibitor showed a substantially reduced efficacy. Furthermore, TR1801-ADC had excellent efficacy with significant antitumor activity in 90% of tested patient-derived xenograft models of gastric, colorectal, and head and neck cancers: 7 of 10 gastric models, 4 of 10 colorectal cancer models, and 3 of 10 head and neck cancer models showed complete tumor regression after a single-dose administration. Altogether, TR1801-ADC is a new generation cMet ADC with best-in-class preclinical efficacy and good tolerability in rats.

Multidrug-resistant and extensively drug-resistant Gram-negative prosthetic joint infections: Role of surgery and impact of colistin administration.

Factors influencing treatment outcome of patients with Gram-negative bacterial (GNB) multidrug-resistant (MDR) and extensively drug-resistant (XDR) prosthetic joint infection (PJIs) were analysed. Data were collected (2000-2015) by 18 centres. Treatment success was analysed by surgery type for PJI, resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) using logistic regression and survival analyses. A total of 131 patients (mean age 73.0 years, 35.9% male, 58.8% with co-morbidities) with MDR (n = 108) or XDR (n = 23) GNB PJI were assessed. The most common pathogens were Escherichia coli (33.6%), Pseudomonas aeruginosa (25.2%), Klebsiella pneumoniae (21.4%) and Enterobacter cloacae (17.6%). Pseudomonas aeruginosa predominated in XDR cases. Isolates were carbapenem-resistant (n = 12), fluoroquinolone-resistant (n = 63) and ESBL-producers (n = 94). Treatment outcome was worse in XDR versus MDR cases (P = 0.018). Success rates did not differ for colistin versus non-colistin in XDR cases (P = 0.657), but colistin was less successful in MDR cases (P = 0.018). Debridement, antibiotics and implant retention (DAIR) (n = 67) was associated with higher failure rates versus non-DAIR (n = 64) (OR = 3.57, 95% CI 1.68-7.58; P < 0.001). Superiority of non-DAIR was confirmed by Kaplan-Meir analysis (HR = 0.36, 95% CI 0.20-0.67) and remained unchangeable by time of infection (early/late), antimicrobial resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) (Breslow-Day, P = 0.737). DAIR is associated with higher failure rates even in early MDR/XDR GNB PJIs versus implant removal. Colistin should be preserved for XDR cases as it is detrimental in MDR infections.

Contribution of an unusual CDR2 element of a single domain antibody in ricin toxin binding affinity and neutralizing activity.

Ricin toxin's enzymatic subunit (RTA) has been subjected to intensive B cell epitope mapping studies using a combination of competition ELISAs, hydrogen exchange-mass spectrometry and X-ray crystallography. Those studies identified four spatially distinct clusters (I-IV) of toxin-neutralizing epitopes on the surface of RTA. Here we describe A9, a new single domain camelid antibody (VHH) that was proposed to recognize a novel epitope on RTA that straddles clusters I and III. The X-ray crystal structure of A9 bound to RTA (2.6 Å resolution) revealed extensive antibody contact with RTA's ß-strand h (732 Å2 buried surface area; BSA), along with limited engagement with α-helix D (90 Å2) and α-helix C (138 Å2). Collectively, these contacts explain the overlap between epitope clusters I and III, as identified by competition ELISA. However, considerable binding affinity, and, consequently, toxin-neutralizing activity of A9 is mediated by an unusual CDR2 containing five consecutive Gly residues that interact with α-helix B (82 Å2), a known neutralizing hotspot on RTA. Removal of a single Gly residue from the penta-glycine stretch in CDR2 reduced A9's binding affinity by 10-fold and eliminated toxin-neutralizing activity. Computational modeling indicates that removal of a Gly from CDR2 does not perturb contact with RTA per se, but results in the loss of an intramolecular hydrogen bond network involved in stabilizing CDR2 in the unbound state. These results reveal a novel configuration of a CDR2 element involved in neutralizing ricin toxin.

Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers.

Bacterial viruses are among the most numerous biological entities within the human body. These viruses are found within regions of the body that have conventionally been considered sterile, including the blood, lymph, and organs. However, the primary mechanism that bacterial viruses use to bypass epithelial cell layers and access the body remains unknown. Here, we used in vitro studies to demonstrate the rapid and directional transcytosis of diverse bacteriophages across confluent cell layers originating from the gut, lung, liver, kidney, and brain. Bacteriophage transcytosis across cell layers had a significant preferential directionality for apical-to-basolateral transport, with approximately 0.1% of total bacteriophages applied being transcytosed over a 2-h period. Bacteriophages were capable of crossing the epithelial cell layer within 10 min with transport not significantly affected by the presence of bacterial endotoxins. Microscopy and cellular assays revealed that bacteriophages accessed both the vesicular and cytosolic compartments of the eukaryotic cell, with phage transcytosis suggested to traffic through the Golgi apparatus via the endomembrane system. Extrapolating from these results, we estimated that 31 billion bacteriophage particles are transcytosed across the epithelial cell layers of the gut into the average human body each day. The transcytosis of bacteriophages is a natural and ubiquitous process that provides a mechanistic explanation for the occurrence of phages within the body.IMPORTANCE Bacteriophages (phages) are viruses that infect bacteria. They cannot infect eukaryotic cells but can penetrate epithelial cell layers and spread throughout sterile regions of our bodies, including the blood, lymph, organs, and even the brain. Yet how phages cross these eukaryotic cell layers and gain access to the body remains unknown. In this work, epithelial cells were observed to take up and transport phages across the cell, releasing active phages on the opposite cell surface. Based on these results, we posit that the human body is continually absorbing phages from the gut and transporting them throughout the cell structure and subsequently the body. These results reveal that phages interact directly with the cells and organs of our bodies, likely contributing to human health and immunity.

Graft copolymers of methyl methacrylate and poly([R]-3-hydroxybutyrate) macromonomers as candidates for inclusion in acrylic bone cement formulations: Compression testing.

Graft copolymers of methyl methacrylate and biodegradable, biocompatible bacterial poly([R]-3-hydroxybutyrate) (PHB) blocks were synthesized and evaluated as possible constituents in acrylic bone cements for use in orthopaedic applications. The copolymers were produced by conventional free radical copolymerization and incorporated in one commercially available acrylic bone cement brand, Antibiotic Simplex (AKZ). Cements with formulations containing 6.7 and 13.5 wt % of PMMA-graft-PHB were prepared. The morphology of the graft copolymer particles was suggested to influence the ability of the modified cement to be processed. Formulations containing more than about 20 wt % of the graft copolymer resulted in cement doughs that, both after first preparation and several hours later, were either sandy or soft spongy in texture and, thus, would be unacceptable for use in orthopaedic applications. The morphologies of the powders and the volumetric porosity (p) and ultimate compressive strength (UCS) of the cured cements were determined. Micro computed tomography showed that the cements presented average porosities of 13.5-16.9%. It was found that, while the powder particle shape and size for the experimental cements were markedly different from those of AKZ, there was no significant difference in either p or UCS for these cements. The latter was determined to be about 85 MPa for the modified cements and 84 MPa for Antibiotic Simplex. Furthermore, the UCS of all the cements exceeded the minimum level for acrylic bone cements, as stipulated by ASTM F-451.

Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: a multicenter open-label controlled randomized study.

OBJECTIVE: Little is known about the optimal duration of antibiotic therapy for diabetic foot osteomyelitis (DFO). This study sought to compare the effectiveness of 6 versus 12 weeks of antibiotic therapy in patients with DFO treated nonsurgically (i.e., antibiotics alone). RESEARCH DESIGN AND METHODS: This was a prospective randomized trial comparing 6- versus 12-week duration of antibiotic treatment. Remission of osteomyelitis during the monitoring period was defined as complete and persistent (>4 weeks) healing of the wound (if present initially), absence of recurrent infection at the initial site or that of adjacent rays, and no need for surgical bone resection or amputation at the end of a follow-up period of at least 12 months after completion of antibiotic treatment. RESULTS: Forty patients followed at five French general hospitals were randomized between January 2007 and January 2009, with 20 treated for 6 weeks and 20 treated for 12 weeks with antibiotics. The two groups were comparable for all variables recorded at inclusion in the study. Remission was obtained in 26 (65%) patients, with no significant differences between patients treated for 6 versus 12 weeks (12/20 vs. 14/20, respectively; P = 0.50). We did not identify any significant parameters associated with patient outcome. Fewer patients treated for 6 weeks experienced gastrointestinal adverse events related to antimicrobial therapy compared with patients treated for 12 weeks (respectively, 15 vs. 45%; P = 0.04). CONCLUSIONS: The present multicenter prospective randomized study provides data suggesting that 6-week duration of antibiotic therapy may be sufficient in patients with DFO for whom nonsurgical treatment is considered.

Synthesis and properties of graft copolymers based on poly(3-hydroxybutyrate) macromonomers.

Graft copolymers of poly(methyl methacrylate) with poly(3-hydroxybutyrate), PHB, segments as long side chains were prepared by the macromonomer method. PHB macromonomers were prepared from the esterification of oligomers with 2-hydroxyethyl methacrylate at their carboxylic acid end. Esterification products displayed low polydispersity indices (ca. 1.2) and a functionality of over 83%, with a Mn of 2,020. Using free radical polymerization methods, the macromonomers were copolymerized with methyl methacrylate to yield graft (comb type) copolymers at different comonomer feed ratios. The graft copolymers contained from 0.5 to 14 mol-% of PHB blocks, with a glass transition temperature decreasing from 100 to 3 degrees C.

Difficult situations managing diabetic foot. Evidences and personal views: is to operate on patients with diabetic foot osteomyelitis old-fashioned?

Both medical and surgical approaches have been shown to be effective in the treatment of patients with diabetic foot osteomyelitis (DFO). In patients with risk factors of bad outcome such as major bone destruction, concomitant acute infections requiring drainage, problems in limb perfusion, highly resistant bacteria, and contraindication for or patient refusal of prolonged antibiotic therapy, the choice of surgery does not require further discussion. On the contrary, modest changes of bone on imaging assessment and no limiting factors as described above make medical treatment an attractive option for patients with DFO provided the rules of antibiotic treatment of chronic osteomyelitis are respected. The key question may not be to oppose surgery and medical treatment but to identify patients who need surgery and those who do not. There is currently no classification or score system that may allow physician to decide whether medical or surgical approach is best adapted to a given patient, and so both experience and skill of the multidisciplinary team appear paramount for guiding the choice of the best adapted ("tailored") strategy in a given patient. In this regard, it would be interesting to compare surgical and medical approaches for DFO that apparently may benefit from one or another (ie, bone lesions seen on plain radiographs of the foot but without bone fragmentation or multiple sites of osteomyelitis, no contraindication to prolonged antibiotic therapy, and location of bone involvement that may allow conservative surgery). Given the current available data on the therapeutic options of DFO, it appears that surgery for those patients is obviously not an old-fashioned option.

A Retrospective Review of the Clinical Experience of Linezolid with or Without Rifampicin in Prosthetic Joint Infections Treated with Debridement and Implant Retention.

INTRODUCTION: Debridement and prosthesis retention, combined with a prolonged antibiotic regimen including rifampicin, is an accepted therapeutic approach when the duration of symptoms is less than 4 weeks and there are no radiological signs of loosening. The outcome of patients managed with this strategy has been previously assessed in several articles with success rates of 60-90%. This study aims to review the clinical experience with linezolid in 3 different hospitals from Spain and France in patients with prosthetic joint infection (PJI) managed with debridement, retention of the implant and treated with linezolid with or without rifampicin. METHODS: Patients with an acute PJI who underwent open debridement with implant retention treated with linezolid for more than 7 days in 3 hospitals from Barcelona, Tours and Lille between 2005 and 2011 were retrospectively reviewed. Relevant information about demographics, co-morbidity, type of implant, surgical treatment, microorganism isolated, antimicrobial therapy, adverse events (AEs) and outcomes were recorded from patients. RESULTS: A total of 39 patients were retrospectively reviewed. The mean age (SD) was 70.5 (8.8) years and 9 patients had diabetes mellitus (23%). There were 25 (64%) knee prostheses, 13 (33%) hips and 1 shoulder (3%). The median interquartile range (IQR) days from arthroplasty to infection diagnosis was 17 (19-48) and 33 (85%) cases were diagnosed within the first 60 days. The median (IQR) duration of antibiotic treatment was 70.5 (34-96) days and the median (IQR) number of days on linezolid treatment was 44.5 (30-81). AEs were observed in 15 patients (38%), with gastrointestinal complaints in 8 cases and anemia in 5 being the most frequent. After a median (IQR) follow-up of 2.5 (1.8-3.6) years, there were 11 failures (28%) (8 relapses and 3 new infections). The failure rate was higher in the rifampicin group (36% vs. 18%) mainly due to a higher relapse rate (27% vs. 12%) although differences were not statistically significant. CONCLUSION: Management of acute PJIs with debridement and retention of the implant linezolid, with or without rifampicin, is associated with a high remission rate and it is an alternative treatment for infections due to fluoroquinolone and/or rifampicin-resistant staphylococci.

Current pharmacotherapy options for osteomyelitis: convergences, divergences and lessons to be drawn.

INTRODUCTION: Antibiotic therapy of osteomyelitis is complex and requires a multidisciplinary approach including surgeons and infectious diseases specialists. However, it suffers from a lack of high-quality clinical studies indicating the superiority of one type of therapy over another. Knowing the antibiotics and their main characteristics is important to guide the choice of treatment for patients with osteomyelitis. AREAS COVERED: The aim of the present article is to review the systemic curative antibiotic therapy of osteomyelitis in adults with a focus on new agents. Diabetic foot osteomyelitis will be briefly discussed separately. A literature search of the PubMed database using the term 'osteomyelitis' alone and in combination with 'hematogenous', 'vertebral', 'biofilm', 'diabetic foot', 'trauma', 'antibiotic' 'daptomycin', 'telavancin', 'tigecycline', 'linezolid', 'ertapenem', 'ceftobiprole' and 'ceftaroline' was carried out. EXPERT OPINION: Antibiotic treatment of acute and chronic osteomyelitis should be considered as two distinct entities with regard to the choice of the most appropriate antibiotics and the need for surgery. Among the most recently available antibiotics, ertapenem and daptomycin are promising agents for the treatment of osteomyelitis due to resistant bacteria.