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Giuseppe Nicoletti

Publications and source records attributed to Giuseppe Nicoletti.

11 recordsLinked to original sources

Molecular alterations of VanA element in vancomycin-resistant enterococci isolated during a survey of colonized patients in an Italian intensive care unit.

To screen for vancomycin-resistant enterococci (VRE) colonization in hospitalized patients and to study molecular evolution and alterations of Tn1546-like elements in VRE among potentially at-risk patients, a 3-year surveillance protocol in an Intensive Care Unit was performed. A total of 397 patients were screened in the period June, 1997-June, 2000, and VRE were isolated from rectal swabs taken at admission, weekly, and when clinically indicated. The susceptibility of the enterococci was determined by the disk diffusion and broth dilution methods. The presence of vancomycin-resistance genes (vanA, vanB, and vanC) was assessed by polymerase chain reaction (PCR); genetic clonality of isolates was assessed by pulsed-field gel electrophoresis (PFGE); Tn1546 types were obtained by restriction fragment length polymorphism (RFLP) analysis of Tn1546 PCR fragments. Thirty-four strains, 31 identified as Enterococcus faecium and 3 strains as E. faecalis, were isolated from 12 of the 397 patients (3.0%); all strains were VanA as assessed by PCR and were resistant to the other antibiotics tested and showed high-level resistance to aminoglycosides. Enterococci isolated during the study period showed that different genetic backgrounds of strains, determined by PFGE combined with RFLP of Tn1546, are present in all the strains isolated in the study. PFGE type B was predominant in 1998 and 1999, and insertion sequence movements were found to have a role in the evolution of VanA resistance elements found in all strains. This study demonstrates that single patients may be colonized by closely related VRE with several PFGE types containing a wide variety of VanA elements. Moreover, isolates with identical PFGE types may contain different VanA elements reflecting rearrangements mediated by insertion sequences in VRE strains during their stay in the gastrointestinal tract.

Adolescent↗

Characterization of clinical isolates of Enterobacteriaceae from Italy by the BD Phoenix extended-spectrum beta-lactamase detection method.

Production of extended-spectrum beta-lactamases (ESBLs) is an important mechanism of beta-lactam resistance in Enterobacteriaceae: Identification of ESBLs based on phenotypic tests is the strategy most commonly used in clinical microbiology laboratories. The Phoenix ESBL test (BD Diagnostic Systems, Sparks, Md.) is a recently developed automated system for detection of ESBL-producing gram-negative bacteria. An algorithm based on phenotypic responses to a panel of cephalosporins (ceftazidime plus clavulanic acid, ceftazidime, cefotaxime plus clavulanic acid, cefpodoxime, and ceftriaxone plus clavulanic acid) was used to test 510 clinical isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Providencia stuartii, Morganella morganii, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Citrobacter freundii, and Citrobacter koseri. Of these isolates, 319 were identified as ESBL producers, and the remaining 191 were identified as non-ESBL producers based on the results of current phenotypic tests. Combined use of isoelectric focusing, PCR, and/or DNA sequencing demonstrated that 288 isolates possessed bla(TEM-1)- and/or bla(SHV-1)-derived genes, and 28 had a bla(CTX-M) gene. Among the 191 non-ESBL-producing isolates, 77 isolates produced an AmpC-type enzyme, 110 isolates possessed TEM-1, TEM-2, or SHV-1 beta-lactamases, and the remaining four isolates (all K. oxytoca strains) hyperproduced K1 chromosomal beta-lactamase. The Phoenix ESBL test system gave positive results for all the 319 ESBL-producing isolates and also for two of the four K1-hyperproducing isolates of K. oxytoca. Compared with the phenotypic tests and molecular analyses, the Phoenix system displayed 100% sensitivity and 98.9% specificity. These findings suggest that the Phoenix ESBL test can be a rapid and reliable method for laboratory detection of ESBL resistance in gram-negative bacteria.

Algorithms↗

No evidence of association between the alpha-2 macroglobulin gene and Parkinson's disease in a case-control sample.

Alpha-2 macroglobulin (A2M) is a component of Lewy bodies, a hallmark of Parkinson's disease (PD). In 159 PD patients and 190 normal controls, we studied two A2M polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method: a five-nucleotide deletion at the 5' splice site of exon 18; and a valine to isoleucine exchange in amino acid position 1000 near the thiolester active site. No significant differences in allelic and genotypic distribution were found between cases and controls or between early and late-onset PD patients. The present data suggest that these polymorphisms do not represent a risk factor for PD and do not modulate the age at onset of PD.

Age Factors↗

Exploring the variability in antibiotic prescribing profiles among paediatricians from two different areas of Italy.

We carried out a multicentre community-based study in order to describe the antibiotic therapeutic approach of paediatricians from two different areas of Italy in the treatment of respiratory tract infection (RTIs), and to assess which factors are involved in a possible variability of prescribing habits. Forty paediatricians participated in the study between October 1998 and April 1999. They had to complete a questionnaire for each therapeutic intervention resulting in an antibiotic prescription. A logistic regression model was used to identify possible predictors in choosing parenteral antibiotics for the treatment of RTIs. In 2 975 questionnaires of antibiotic treatment, RTIs represented 90.2% of the total antibiotics used. Upper respiratory tract infections were the most commonly treated diagnostic group (59.6%), followed by lower respiratory tract infections (20.4%), and middle ear infections (19.8%). Statistically significant differences between northern and southern Italy were reported in the antibiotic prescription profile and the duration of the therapy. Another marked difference was reported in the frequency of laboratory analysis requests. The logistic regression model indicated that the use of parenteral antibiotics appears significantly related to the type of infections [lower RTIs: (OR: 3.99; 95% CI: 2.49-6.37)], the geographic location [northern Italy: (OR: 0.20; 95% CI: 0.20-0.39)], and the presence of concurrent diseases (OR: 3.21; 95% CI: 1.46-7.02). The lack of adherence to clinical guidelines and the marked variability of antibiotic prescription rates between different areas of the country appear to be related to factors other than bacterial resistance, and highlight the importance of carrying out educational programmes targeted at the national level for improving the antibiotic prescription habits for the treatment of RTIs.

Anti-Bacterial Agents↗

A large family with pure autosomal dominant hereditary spastic paraplegia from southern Italy mapping to chromosome 14q11.2-q24.3.

A large Italian pedigree from southern Italy with autosomal dominant uncomplicated spastic paraplegia is reported. The clinical picture was uniform and characterized by insidiously progressive lower extremity weakness and spasticity. The mean age at onset of symptoms was 8.3 years. Significant linkage to the SPG3 locus on chromosome 14 was detected. The authors also report their search for mutations in a gene located in the region and its exclusion as a candidate for SPG3.

Adult↗

Prevalence of extended spectrum beta-lactamases among Enterobacteriaceae: an Italian survey.

The prevalence of extended-spectrum beta-lactamase (ESBL) production by consecutive non-repeated isolates of Enterobacteriaceae was determined over a 6-month period. A total of 8015 strains were isolated from ten Italian laboratories and 509 (6.3%) of these were designated ESBL producers from the results of a double-disk synergy test. Escherichia coli was the most isolated microrganism, followed by Klebsiella pneumoniae and Proteus mirabilis. Providencia stuartii (28.1%) was the most frequently isolated ESBL producer, followed by K. pneumoniae and Enterobacter aerogenes (20.5%). However, amongst all ESBL producers, K. pneumoniae (38.2%) was the most represented followed by P. mirabilis (25.7%). All the strains positive to DD tests were confirmed for the carriage of TEM and SHV genes using colony-blot hybridisation (CH). A total of 447 strains (88.0%) were CH-positive, of which 42.3% hybridised with the TEM-type probe, 30.1% with the SHV-type probe and 15.6% with both probes. In conclusion, our findings indicate that 6.3% of all Enterobacteriaceae tested produced ESBLs, 42.3% of which were TEM-derived enzymes. More than 20% of P. stuartii, K. pneumoniae and E. aerogenes harbour these enzymes. The double-disk test seems to be a useful test to identify ESBL producing strains.

Anti-Bacterial Agents↗

Molecular characterization of extended-spectrum beta-lactamases produced by nosocomial isolates of Enterobacteriaceae from an Italian nationwide survey.

Extended-spectrum beta-lactamases (ESBLs) are widespread in hospital settings worldwide. The present investigation was undertaken to assess the distribution and prevalence of ESBLs belonging to the TEM and SHV families in 448 ESBL-producing clinical isolates of Enterobacteriaceae collected from 10 different Italian hospitals. The natures of TEM and SHV determinants were identified by direct sequencing of PCR-amplified genes. TEM-52 and SHV-12 were the most common variants, and they were found in most hospitals and in several different species. Other less frequent variants included TEM-5, TEM-12, TEM-15, TEM-19, TEM-20, TEM-24, TEM-26, TEM-43, TEM-60, TEM-72, TEM-87, SHV-2a, SHV-5, and SHV-11. Proteus mirabilis was the most common producer of TEM-type ESBLs, while Klebsiella pneumoniae was the most common producer of SHV-type ESBLs. The distribution of TEM- and SHV-type ESBL variants in Enterobacteriaceae from Italian hospitals exhibited notable differences from those from other geographical settings.

Cross Infection↗

Recent developments in carbapenems.

Carbapenems are beta-lactam antibiotics characterised by the presence of a beta-lactam ring with a carbon instead of sulfone in the 4-position of the thyazolidinic moiety. The first carbapenem to be utilised in therapy was imipenem, the N-formimidoyl derivative of thienamycin. Imipenem is coadministered with cilastatin, an inhibitor of human renal dehydropeptidase I, as imipenem is hydrolysed by this enzyme. Meropenem was the first carbapenem with a 1-beta-methyl group and 2-thio pyrrolidinyl moiety, which renders this antibiotic stable to renal dehydropeptidase I. Other carbapenems for parenteral administration later discovered include biapenem, panipenem, ertapenem, lenapenem, E-1010, S-4661 and BMS-181139. Carbapenems which are orally administered include sanfetrinem, DZ-2640, CS-834 and GV-129606. Carbapenems have an ultra-broad spectrum of antibacterial activity and stability to almost all clinically relevant beta-lactamases. This differentiates them from all other currently available classes of beta-lactam antibiotics. However, Class B beta-lactamases, along with some rare Class A and D enzymes, are able to hydrolyse these antibiotics. Although Class B enzymes are generally chromosomally-encoded (isolated from Stenotrophomonas maltophilia, Aeromonas spp., Bacillus cereus, Bacteroides fragilis, Flavobacterium spp. and Legionella gormanii), plasmid-metallo-beta-lactamases now are appearing in B. fragilis, Pseudomonas aeruginosa, Acinetobacter baumannii and members of Enterobacteriaceae such as Serratia marcescens and Klebsiella pneumoniae. The number of these enzymes compared to the number of other beta-lactamase types is still low, however, it is likely that they will spread due to the increased selective pressure of carbapenem use. The very broad spectrum of antimicrobial activity associated with a good clinical efficacy and a favourable safety profile makes the carbapenems valuable as 'first-line' antibiotics in initial empirical therapy for the treatment of severe infections.

Bacterial Infections↗

Body weight influences pharmacokinetics of levodopa in Parkinson's disease.

Changes in body weight may induce substantial variations in peripheral pharmacokinetics of drugs, but the relation between body weight and levodopa (LD) pharmacokinetics has never been investigated in Parkinson's disease. To address this issue, we conducted a pharmacokinetic study with 164 patients with sporadic Parkinson's disease. Patients underwent an oral acute LD test with 250 mg of LD, and pharmacokinetic variables were assessed at baseline and at 30, 60, 120, and 240 minutes after LD administration. Plasmatic-LD areas under the curve and body weight were significantly and inversely correlated as well as the elimination of the half-life of LD and body weight. In our sample, women were significantly lighter and had a significantly greater area under the curve than men. Moreover, a greater percentage of women showed LD peak-dose dyskinesias compared with men. Our findings suggest that lighter patients with Parkinson's disease probably receive a greater cumulative dosage of LD per kilogram of body weight during long-term treatment, because in clinical practice, LD is administered without any adjustment of the dose to body weight. This could explain gender differences for the development of LD-induced peak-dose dyskinesias observed during the course of the disease.

Aged↗