Italian National Health Institute

Rome, Italy

Italian National Health Institute

Rome, Italy
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Giani T.,University of Siena | Antonelli A.,University of Florence | Caltagirone M.,University of Pavia | Mauri C.,A Manzoni Hospital | And 23 more authors.
Eurosurveillance | Year: 2017

Extended-spectrum beta-lactamases (ESBLs), AmpCtype beta-lactamases (ACBLs) and carbapenemases are among the most important resistance mechanisms in Enterobacteriaceae. This study investigated the presence of these resistance mechanisms in consecutive non-replicate isolates of Escherichia coli (n = 2,352), Klebsiella pneumoniae (n = 697), and Proteus mirabilis (n = 275) from an Italian nationwide cross-sectional survey carried out in October 2013. Overall, 15.3% of isolates were non-susceptible to extended-spectrum cephalosporins but susceptible to carbapenems (ESCR-carbaS), while 4.3% were also non-susceptible to carbapenems (ESCR-carbaR). ESCR-carbaS isolates were contributed by all three species, with higher proportions among isolates from inpatients (20.3%) but remarkable proportions also among those from outpatients (11.1%). Most ESCRcarbaS isolates were ESBL-positive (90.5%), and most of them were contributed by E. coli carrying blaCTX-M group 1 genes. Acquired ACBLs were less common and mostly detected in P. mirabilis. ESCR-carbaR isolates were mostly contributed by K. pneumoniae (25.1% and 7.7% among K. pneumoniae isolates from inpatients and outpatients, respectively), with blaKPC as the most common carbapenemase gene. Results showed an increasing trend for both ESBL and carbapenemase producers in comparison with previous Italian surveys, also among outpatients. © 2017, European Centre for Disease Prevention and Control (ECDC). All rights reserved.


Maisetta G.,University of Pisa | Vitali A.,CNR Institute of Chemistry of Molecular Recognition | Scorciapino M.A.,University of Cagliari | Rinaldi A.C.,University of Cagliari | And 9 more authors.
FEBS Journal | Year: 2013

The human hepcidin 25 (hep-25) and its isoform hepcidin 20 (hep-20) are histidine-containing, cystein rich, β-sheet structured peptides endowed with antimicrobial activity. We previously reported that, similar to other histidine-containing peptides, the microbicidal effects of hep-25 and hep-20 are highly enhanced at acidic pH. In the present study, we investigated whether pH influences the mode of action of hep-25 and hep-20 on Escherichia coli American Type Culture Collection 25922 and model membranes. A striking release of β-galactosidase by hepcidin-treated E. coli was observed at pH 5.0, whereas no inner membrane permeabilization capacity was seen at pH 7.4, even at bactericidal concentrations. Similar results were obtained by flow cytometry when assessing the internalization of propidium iodide by hepcidin-treated E. coli. Scanning electron microscope imaging revealed that both peptides induced the formation of numerous blebs on the surface of bacterial cells at acidic pH but not at neutral pH. Moreover, a phospholipid/polydiacetylene colourimetric vesicle assay revealed a more evident membrane damaging effect at pH 5.0 than at pH 7.4. The leakage of entrapped dextrans of increasing molecular size from liposomes was also assessed at pH 7.4. Consistent with the lack of β-galactosidase release from whole E. coli observed at such a pH value, evident leakage of only the smallest 4-kDa dextran (and not of dextrans of 20 or 70 kDa) was observed, indicating a poor ability of hepcidin peptides to permeabilize liposome vesicles at pH 7.4. Altogether, the data obtained in the present study using different approaches strongly suggest that the ability of hepcidins to perturb bacterial membranes is markedly pH-dependent. The human hepcidin 25 (hep-25) and its isoform hepcidin 20 (hep-20) are histidine-containing, cystein rich, β-sheet structured peptides endowed with antimicrobial activity which is highly enhanced at acidic pH. The data obtained by using different approaches strongly suggested that the mode of hep-25 and hep-20 action and their ability to perturb Escherichia coli and model membranes is markedly pH-dependent. © 2013 FEBS.


Gallina P.,University of Florence | Paganini M.,University of Florence | Biggeri A.,University of Florence | Biggeri A.,ISPO Cancer Prevention and Research Institute | And 15 more authors.
Stereotactic and Functional Neurosurgery | Year: 2014

Background: Restoration of functions in Huntington's disease (HD) by neurotransplantation stems from the formation of a striatum-like structure capable of establishing host connections as a result of grafted striatal neuroblast maturation. For the first time, we demonstrated some developmental steps accomplished by progenitor cells in the brain of an HD patient and analysed the molecular asset of the human primordium. Case Report: Surgery involved bilateral (two sessions) stereotactic, caudate-putaminal transplantation of whole ganglionic eminence fragments from single legally aborted fetuses. MRI showed that the tissue deposits of the left hemisphere grew and joined to constitute a single tissue mass that remodelled basal ganglia anatomy and remained stable in size over time. No evidence of graft growth was observed contralaterally. PET demonstrated increased striatal and stable cortical metabolism. Unified Huntington's Disease Rating Scale assessments demonstrated improvement of motor performances, which faded over the 36-month follow-up. Cognitive performance tended to decrease at a lower rate than before transplantation. Conclusion: The striatal primordium grew into the host brain and this process was associated with metabolic change and some clinical benefit. The study suggests the plasticity and reparative potential of un-manipulated primordium in an era where promising cell-based therapies are still in their infancy. © 2014 S. Karger AG, Basel.


Paganini M.,University of Florence | Biggeri A.,University of Florence | Biggeri A.,ISPO Cancer Prevention and Research Institute | Romoli A.M.,University of Florence | And 16 more authors.
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2014

Objective: To assess the clinical effect of caudateputaminal transplantation of fetal striatal tissue in Huntington 's disease (HD). Methods: We carried out a follow-up study on 10 HD transplanted patients and 16 HD not-transplanted patients. All patients were evaluated with the Unified HD Rating Scale (UHDRS) whose change in motor, cognitive, behavioural and functional capacity total scores were considered as outcome measures. Grafted patients also received morphological and molecular neuroimaging. Results: Patients were followed-up from disease onset for a total of 309.3 person-years (minimum 5.3, median 11.2 years, maximum 21.6 years). UHDRS scores have been available since 2004 (median time of 5.7 years since onset, minimum zero, maximum 17.2 years). Median post-transplantation follow-up was 4.3 years, minimum 2.8, maximum 5.1 years. Adjusted posttransplantation motor score deterioration rate was reduced compared to the pretransplantation period, and to that of not-transplanted patients by 0.9 unit/years (95% CI 0.2 to 1.6). Cognitive score deterioration was reduced of 2.7 unit/years (95% CI 0.1 to 5.3). For grafted patients the 2-year post-transplantation [18F] fluorodeoxyglucose positron emission tomography (PET) showed striatal/cortical metabolic increase compared to the presurgical evaluation; 4-year post-transplantation PET values were slightly decreased, but remained higher than preoperatively. [123I]iodobenzamide single photon emission CT demonstrated an increase in striatal D2-receptor density during postgrafting follow-up. Conclusions: Grafted patients experienced a milder clinical course with less pronounced motor/cognitive decline and associated brain metabolism improvement. Life-time follow-up may ultimately clarify whether transplantation permanently modifies the natural course of the disease, allowing longer sojourn time at less severe clinical stage, and improvement of overall survival.


Giani T.,University of Siena | Pini B.,A Manzoni Hospital | Arena F.,University of Siena | Conte V.,University of Siena | And 7 more authors.
Eurosurveillance | Year: 2013

Carbapenem-resistant Enterobacteriaceae (CRE) are emerging as a public health problem in various settings. In Italy, a rapid and remarkable increase of carbapenem-non-susceptible Klebsiella pneumoniae has been reported since 2010. Here we report on the results of a countrywide cross-sectional survey, carried out from 15 May to 30June 2011 to investigate the diffusion of CRE in Italy and to characterise the most prevalent resistance mechanisms and their dissemination patterns. CRE were reported from most (23 of 25) participating laboratories, with an overall proportion of 3.5% and 0.3% among consecutive non-duplicate clinical isolates of Enterobacteriaceae from inpatients (n=7,154) and outpatients (n=6,595), respectively. K. pneumoniae was the most frequent species (proportion of carbapenem-non-susceptible isolates: 11.9%), while a minority of CRE of other species were detected. Carbapenemase production was detected in the majority (85%) of CRE. KPC-type enzymes were by far the most common (89.5% of carbapenemase producers), followed by VIM-1 (9.2%) and OXA-48 (1.3%). KPC-producing K. pneumoniae (KPC-KP) were detected in most centres and contributed majorly to the epidemic dissemination of CRE recently observed in our country. Dissemination of KPC-KP was mostly sustained by strains of clonal complex 258 (ST-258 producing KPC-2 or KPC-3, and ST-512 producing KPC-3), while a minority belonged to ST-101.


Belleudi V.,Rome e Health Authority | Faustini A.,Rome e Health Authority | Stafoggia M.,Rome e Health Authority | Cattani G.,Institute for Environmental Protection and Research | And 3 more authors.
Epidemiology | Year: 2010

BACKGROUND: Little is known about the short-term effects of ultrafine particles. METHODS: We evaluated the effect of particulate matter with an aerodynamic diameter ≤10 μm (PM10), ≤2.5 μm (PM2.5), and ultrafine particles on emergency hospital admissions in Rome 2001-2005. We studied residents aged ≥ 35 years hospitalized for acute coronary syndrome, heart failure, lower respiratory tract infections, and chronic obstructive pulmonary disease (COPD). Information was available for factors indicating vulnerability, such as age and previous admissions for COPD. Particulate matter data were collected daily at one central fixed monitor. A case-crossover analysis was performed using a time-stratified approach. We estimated percent increases in risk per 14 μg/m3 PM10, per 10 μg/m3 PM 2.5, and per 9392 particles/mL. RESULTS: An immediate impact (lag 0) of PM2.5 on hospitalizations for acute coronary syndrome (2.3% [95% confidence interval = 0.5% to 4.2%]) and heart failure (2.4% [0.3% to 4.5%]) was found, whereas the effect on lower respiratory tract infections (2.8% [0.5% to 5.2%]) was delayed (lag 2). Particle number concentration showed an association only with admissions for heart failure (lag 0-5; 2.4% [0.2% to 4.7%]) and COPD (lag 0; 1.6% [0.0% to 3.2%]). The effects were generally stronger in the elderly and during winter. There was no clear effect modification with previous COPD. CONCLUSIONS: We found sizeable acute health effects of fine and ultrafine particles. Although differential reliability in exposure assessment, in particular of ultrafine particles, precludes a firm conclusion, the study indicates that particulate matter of different sizes tends to have diverse outcomes, with dissimilar latency between exposure and health response. © 2010 by Lippincott Williams & Wilkins.

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