R. Di Rosa

New polymer-antibiotic systems to inhibit bacterial biofilm formation: A suitable approach to prevent central venous catheter-associated infections

Abstract Intravascular catheters are widely employed in medical practice. However, complications such as local or systemic infections are frequently related to their use. The significant increase in this type of nosocomial infection has prompted the search for new strategies to prevent them. This paper reports on an experimental model to prevent catheter-related infections based on the adsorption of a beta-lactam antibiotic (cefamandole nafate) on functionalized urethane polymers. The polyurethanes synthesized were used to coat a commercial central venous catheter. The influence of functional groups on the polymer-antibiotic interaction was analyzed and the kinetics of the antibiotic release from the catheters was dynamically studied. We were able to realize a polymer-antibiotic system able to inhibit bacterial growth up to 7 days. These promising results have encouraged us to extend this experimental model to other polymer-antibiotic systems in order to identify those allowing bacterial growth inhibition for longer times.

Polyurethanes Loaded with Antibiotics: Influence of Polymer-Antibiotic Interactions on In Vitro Activity Against Staphylococcus epidermidis

Abstract Acidic or basic polyurethanes were loaded with antibiotics to develop materials to prevent medical device-related infections. A correlation between polymer-antibiotic interactions and amount of drug absorbed by polymers and released over time was found. Since the employed antibiotics, i.e. amoxicillin, cefamandole nafate, rifampin and vancomycin, possessed at least an acidic group in their structural formula, the introduction of basic tertiary amines in the polyurethane side-chain resulted in an increased polymer ability to adsorb antibiotics. However, a stronger ionic interaction between this polymer and the antibiotics caused a release of lower amount of drug over time. Antibiotics released from polymers inhibited Staphylococcus epidermidis growth on agar. Antibiotic-loaded polyurethanes kept in water for increasing times were still able to show inhibition zones of bacterial growth. The antibacterial activity lasted up to 3 hours for amoxicillin, 24 hours for vancomycin, 8 days for cefamandole nafate and 8 months for rifampin.

Polyclonal intravenous immunoglobulin: An important additional strategy in sepsis?

Sepsis syndrome is characterized by a systemic inflammatory response to infection potentially leading to acute organ failure and rapid decline to death. Polyclonal intravenous immune globulin, a blood product derived from human donor blood, in addition to antiinfective activities, also exerts a broad antiinflammatory and immunomodulating effect. Intravenous immunoglobulin (IVIg) has been proposed as adjuvant therapy for sepsis even though the clinical studies demonstrating their efficacy and safety are relatively small. Several systematic reviews and meta-analyses of intravenous immunoglobulin treatment in sepsis have been performed. As a result of heterogeneity across studies and inconsistencies in results, the majority have concluded that more evidence, coming from large, well-conducted randomized controlled trials (RCTs), is required. Moreover the appropriate timing of administration and the identification of specific clinical settings represent a key factor to maximizing their beneficial effect. The authors, in this revision, review the basic mechanisms of action of IVIg, the rationale for their use, and their clinical applications.

Infections by ampicillin-resistant enterococci : a case-control study

We identified 17 (20%) of 83 consecutive enterococcal isolates from hospitalized patients with documented infection as high-level ampicillin-resistant enterococci (ARE). Of these, 16 isolates were identified as Enterococcus faecium and 1 isolate as Enterococcus raffinosus. A case-control study found no significant differences with respect to underlying diseases, central venous catheterization, nosocomial acquisition of the infection and sites of infection. Patients with ARE infection were older and had a higher inhospital fatality rate than those with ampicillin-susceptible Enterococcus (ASE) infection. Hospitalization in a surgery service (usually for an abdominal procedure), prolonged hospital stay, prior treatment with antibiotics (in particular imipenem and metronidazole), were also more frequent among patients with ARE infection. ARE isolates were more frequently resistant to imipenem, ciprofloxacin and streptomycin than ASE isolates.

The Absorption of Cephalosporin on Vinyl Polymers to Form Antibacterial Surfaces

In order to obtain antimicrobial polymer compositions potentially suitable for catheter fabrication, a cephalosporin was bonded to ethylene-vinyl alcohol copolymers and to their derivatives containing hydrophilic positively or negatively charged groups. The polymers were characterized by chemical and physico-chemical techniques. The antibiotic was adsorbed at a density of 1.3 mg/cm2 onto the unaffected polymer surface. The density was increased up to 1.78 mg/cm2 when the polymer was derivatized. The elution rate of the antibiotic from the surfaces and its antimicrobial activity were determined. The underivatized polymer has shown antimicrobial activity for 24 h whereas the carboxylated polymer was active for 72 h. During this time 32% of the antibiotic was eluted from the underivatized polymer and approximately 15% from the derivatized polymer.

SAT0282 Autoimmunity and pregnancy: evidence from an observational study

Background Obstetrical APS is defined by positive aPLs and a history of one or more unexplained deaths of morphologically normal fetus at or beyond the 10th week of gestation (WG) or one or more consecutive spontaneous abortions before the 10th WG. Also one or more premature birth before 34 WG because of eclampsia, severe pre-eclampsia, or recognized features of placental insufficiency represent one of the diagnostic criteria (1). Infertility is defined as the inability of a couple practicing frequent intercourse and not using contraception to conceive a child after 12 months. Autoimmune diseases are not inclued among major causes of infertility, despite defective embryonic implantation could be considered an aspect of recurrent fetal losses in patients with positive antiphospholipid antibodies, due to their capabilities to reduce trophoblast prolipheration and growth (2). Objectives The aim of our study was to evaluate the prevalence of aPLs and pregnancy outcome in a population of women undergoing in vitro fertilization. Methods from December 2012 to December 2016, we selected 75 consecutive patients undergoing in vitro fertilization and evidence positive autoantibodies. Each of them was evaluated for genetic, anatomic, hormonal and infective causes of infertility. Moreover antinuclear antibodies (ANA), anticardiolipin antibodies (aCL), anti-β2-glycoprotein I (GP1), lupus anticoagulant (LA) and extractable nuclear antigens (ENA) profile were assessed. Results patients mean age was 41.38±4.87 years, ranging from 31 to 53 years. Prevalence of aPLs in our population was 68%. All women showed at least twice positive aPLs. aCL IgM and LA were the main antibody populations observed. ANA were positive in 50% of women, whereas SSA or SSB were positive in 4.17%. In 22.9% of patients a systemic autoimmune disease was newly diagnosed, mainly systemic lupus erythematosus. All patients with hystory of recurrent miscarriages and positive aPL were treated with subcutaneous low weight heparin plus daily oral acetylsalicylic acid (ASA 100 mg) (3). Full term pregnancy was obtained in 45.8% of patients. Conclusions Prevalence of aPLs in the general population is 1–5%, whereas in our selected series positive aPLs were detected in 68% of the patients, suggesting that prevalence of aPLs may be increased in infertile patients (4). Moreover, a systemic autoimmune disease was newly diagnosed in 22.9% of patients suggesting that paucisimptomatic disease can be underestimated. Finally we would suggest that treating autoimmune co-morbidities ameliorates implantation rates in women undergoing in vitro fertilization (5). References Miyakis S, Lockshin MD, Atsumi T, et al. J Thromb Haemost 2006; 4:295–306. Chinhizola CB, de Jesus GR.A. Lupus 2014; 23:1232–1238. Proietta M, Ferrero S, Del Porto F. Lupus 2014;23:724–725. AndreoliL, Bertsias GK, Agmon-Levin N et al. Ann Rheum Dis. 2016;30:133–148. Kocku A, Yavuz E, CeliK H,Bildircin D. Arch Gynecol Obstet 2012;286:1283–1289. Disclosure of Interest None declared

AB0391 Immunogenicity of 13-Valent Conjugate Pneumococcal Vaccine in Patients with Rheumatoid Arthritis

Background Vaccine administration is an effective tool to prevent infectious diseases. Patients with autoimmune diseases have a higher risk of infections -mainly at respiratory level- as a consequence of immune system dysregulation as well as of immunosuppressive treatment. Therefore, prevention by specific available vaccinations is crucial, as suggested by different studies and by EULAR and ACR recommendations. To date, literature data support the effectiveness of vaccinations with pneumococcal polysaccharide vaccine in patients with Rheumatoid Arthritis (RA); on the contrary, the 13-valent conjugate pneumococcal vaccine has not yet been studied in RA patients receiving immunosuppressive treatment. Objectives The aim of this study was to evaluate the immunogenicity of the 13-valent conjugate pneumococcal vaccine in patients with RA receiving Methotrexate (MTX)+TNF blockers, MTX alone or TNF blockers monotherapy compared to healthy controls (HC). The secondary objective was to determine vaccine safety. Methods Consecutive RA patients with low-moderate disease activity treated with stable dose of glucocorticoids, MTX and/or anti-TNF drugs were enrolled. The pneumococcal vaccine was administered intramuscularly at baseline visit; patients underwent clinical and laboratory evaluation at the time of vaccination (T0) and after 1 (T1) and 6 (T2) months. Blood samples for the evaluation of specific anti-pneumococcal antibodies were collected at the same time-points. The immunogenicity was evaluated with the enzyme-linked immunosorbent assay (ELISA). Data were expressed as mean ± standard deviation; t-test was used to evaluate the difference in serum levels of antibodies to pneumococcal antigens at 1 and 6 months compared to baseline values. A p value <0.05 was considered statistically significant. Results 38 patients [36F/2M, age 62.1±11 yrs] and 6 healthy controls [2F/4M age 63.7±2 yrs] were enrolled; 11 patients were treated with MTX alone, 12 with TNF blocking monotherapy (Etanercept n=7, Adalimumab n=3 and Certolizumab n=2) and 15 with MTX in combination with TNF blockers (Infliximab n=1, Etanercept n=6, Adalimumab n=6 and Golimumab n=2). Actually, 24 patients and 3 HC have completed 6 months of follow-up. More than half of patients (61%) developed a positive antibody response to the thirteen polysaccharides (twofold increase of antibody titer). The most immunogenic pneumococcal antigens were polysaccharides 1, 4 and 9V (Image 1). At 1 month a threefold increase in antibody titre with a protective level maintained throughout 6 months was observed. After 1 and 6 months of treatment, no significant change in DAS28 was observed in vaccinated patients. During the follow-up we did not observe any severe adverse reactions in RA patients nor in healthy controls. Mild systemic and local adverse events (redness and/or swelling of injection site) were reported by 44% of vaccinated RA patients and by 16% of healthy subjects. Conclusions This is the first preliminary study to demonstrate safety and immunogenicity of the 13-valent conjugate pneumococcal vaccine in RA patients on immunosuppressive treatment. Disclosure of Interest None declared

AB0286 Biological drugs in chronic inflammatory arthropathies: discontinuation rate of first anti-tnf treatment.

Background Anti-TNF drugs revolutioned inflammatory arthropathies treatment, cutting down their clinical evolution and giving rise to remarkable benefits in patients life quality. Objectives It has been carried out a retrospective study to evaluate the correlations with demographic data and clinical parameters in patients suffering of arthritis rheumatoid (RA) or psoriatic arthritis (PsA) in case of interruption of the first anti-TNF drug treatment. Methods From November 2004 to October 2011, 239 patients affected by RA (n=165), PsA (n=74) have been recruited for first anti-TNF drug treatment For every patient have been weighed: age, sex, pre-therapy illness activity, evaluated by DAS44, selected anti-TNF drug (infliximab, etanercept, adalimumab), interruptions of the treatment and their causes, divided in adverse events, inefficacy, and other ones (pregnancy, poor compliance, surgical operations etc.). The patients that did not interrupt the treatment have been defined as Responder and those who stop it or who make a switch as Non Responder. A statistical assessment about the possible correlation between Responder/Non Responder condition, different drugs used and demographic and clinical parameters was made by Chi-Quadro and T-Student tests. Results 110 of the 239 patients (46%) stopped the treatment with the first anti-TNF drug: 45% (n=74) patients with RA, 49% (n=36) with PsA. Statistically significant differences are not recorded among global rate of patients who interrupt etanercept (56% n=63), infliximab 50% (n=17) and adalimumab 50% (n=30). A more detailed analysis among the stopping reasons found adverse events in the 22% of the cases (n=52), ineffectiveness in 13% (n=32), and other causes in 9.2% (n=26). Infliximab showed the onset of adverse events in 38% of cases (13 pts) in comparison to 19% (28 pts) for etanercept and to 18% (11 pts) for adalimumab. Etanercept appears to be associated with a statistically significant lower occurrence of discontinuation for adverse events, compared to infliximab (p<0.03). Comparing to same factor adalimumab vs infliximab we obtain a correlation near to statistical significance (p<0.054). Among the analyzed demographic and clinical parameters, pre-treatment disease activity showed a statistical correlation with first anti-TNF interruption: Non Responder patients with RA e PsA presented a higher value of DAS respect to the Responder ones (p<0.005); the group of the Non Responder patients showed a longer duration of illness respect the group of Responder patients (p<0.052). Conclusions Infliximab is associated to higher discontinuation rate for adverse events, in comparison with etanercept and adalimumab. Among evaluated demographic and clinical data, duration of illness and high disease activity to recruitment seem to negatively affects the answer to the first anti-TNF, suggesting that such parameters may have predictive value for the interruption of the drug. Disclosure of Interest None Declared