Davide Oggioni

The presence of Epstein-Barr Virus (EBV) DNA in cerebrospinal fluid (CSF) and peripheral blood (PB) samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS) and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC) positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples. Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity.

Linezolid is the main representative of the oxazolidinones, introduced in 2000 in clinical practice to treat severe Gram-positive infections. This compound inhibits protein synthesis by binding to the peptidyl transferase centre of the 50S bacterial ribosomal subunit. The aim of this study was to characterize 12 clinical strains of linezolid-resistant Staphylococcus spp. isolated in Northern Italy. All isolates of Staphylococcus spp. studied showed a multi-antibiotic resistance phenotype. In particular, all isolates showed the presence of the mecA gene associated with SSCmec types IVa, V or I. Mutations in domain V of 23S rRNA were shown to be the most prevalent mechanism of linezolid resistance: among these a new C2551T mutation was found in S. aureus, whilst the G2576T mutation was shown to be the most prevalent overall. Moreover, three S. epidermidis isolates were shown to have linezolid resistance associated only with alterations in both L3 and L4 ribosomal proteins. No strain was shown to harbor the previously described cfr gene. These results have shown how the clinical use of linezolid in Northern Italy has resulted in the selection of multiple antibiotic-resistant clinical isolates of Staphylococcus spp., with linezolid resistance in these strains being associated with mutations in 23S rRNA or ribosomal proteins L3 and L4.

<em>Background and aims:</em> Ceftobiprole is a new cephalosporin characterized by a potent activity against Gram-positive and Gram-negative bacterial pathogens. It is noting that ceftobiprole has a strong affinity for penicillin binding proteins including PBP 2A, which mediates resistance to beta-lactams in methicillin (oxacillin)-resistant coagulase- negative staphylococci and <em>Staphylococcus</em> aureus (MRSA). The aim of the current study was to examine the antimicrobial activity of <em>ceftobiprole</em> against clinical isolates of <em>S</em>. <em>aureus</em> recently collected at our institution. <br /><em>Materials and methods:</em> One hundred and forty blood isolates of<em> S. aureus</em> were evaluated, including methicillin-susceptible (MSSA, n=70) and MRSA (n=70) strains. Twenty additional MRSA isolates obtained from different sites (including skin and soft tissues, blood, and lower respiratory tract) and characterized by borderline susceptibility to vancomycin were also studied to assess the ability of ceftobiprole to overcome this worrisome trait. MIC values of ceftobiprole were determined by Etest strips and results were interpreted according to EUCAST guidelines. <em><br />Results and conclusions:</em> Study isolates were consistently susceptible to ceftobiprole, with MIC values ranging from 0.125 mg/L to 2 mg/L. Overall, MIC50 and MIC90 were 0.25 mg/L and 0.5 mg/L, respectively. Ceftobiprole showed in vitro activity against all S. aureus isolates, with small differences among groups selected on the basis of resistance to methicillin and/or reduced susceptibility to vancomycin. Thus, ceftobiprole appears a valid choice for treating infections caused by<em> S. aureus</em>, even when susceptibility results are not yet available. Additionally, ceftobiprole may be a valid option in the case of reduced susceptibility to vancomycin.