This paper reports the data concerning the net economic cost savings attributable to influenza vaccination in healthy children aged 2-5 years, and may be useful when deciding the best recommendations for the use of influenza vaccine in pediatrics. A total of 303 previously unprimed healthy children aged 2-5 years (163 males; mean age +/- S.D.: 3.22 +/- 2.43 years) were prospectively, blindly randomised in a 2:1 ratio to receive two doses of an inactivated, trivalent, virosome-formulated subunit influenza vaccine (Inflexal V, Berna Biotech, Berne, Switzerland) or no vaccination. The results show that influenza vaccination of healthy children aged 2-5 years Substantially reduces influenza-like illnesses and related costs in the children themselves and their families. However, larger and longer running study spanning multiple seasons may be warranted before Suggesting the universal vaccination of this group Of Subjects. (c) 2005 Elsevier Ltd. All rights reserved.

This prospective study compared the clinical and socio-economic impact of laboratory-confirmed influenza and respiratory syncytial virus (RSV) infection on healthy children and their families. Among 1520 otherwise healthy children aged < 15 years attending the Emergency Department for acute conditions other than trauma, influenza viruses and RSV were found in 234 (15.4%) and 116 (7.6%; p < 0.0001) patients, respectively. The fact that influenza has a similar global clinical impact on the community to that of RSV infection, but represents a greater socio-economic burden, may contribute to broadening the acceptance of influenza vaccination.

To improve the knowledge on influenza and respiratory syncytial virus (RSV) infections burden on paediatric population, a cohort of 1600 Italian children was prospectively followed up during the 2001–2002 and 2002–2003 winters. Specimens from each influenza-like illness (ILI) were collected and tested for influenza viruses and RSV by PCR and cell cultures. Two hundred sixty-eight and 440 episodes of ILI were registered during 2001–2002 and 2002–2003, with a cumulative incidence of 16.8% and 27.5%, respectively. A comparison between the morbidity data of this well-studied cohort and those of the national network (Influnet) and the one between different swabs and different detection methods was performed. Considering the high variability of respiratory epidemics in different areas, the cumulative morbidity is not far from that observed in the Liguria region by the national network (21.1% and 24.6%). Fifty-nine (22%) and 22 (8.3%) out of 268 specimens collected during 2001/2002 season and 60 (13.6%) and 34 (7.2%) out of 440 during 2002/2003 were influenza and RSV-PCR positive, respectively. During the former winter, influenza B virus was prominent, while during the last season A/H3N2 predominated. RSV circulation preceded influenza detection in both seasons. PCR confirmed higher sensitivity than cell culture in influenza virus detection; the combination of a paediatric sentinel-based network with virological surveillance performed by reverse transcription polymerase chain reaction (RT-PCR) for influenza and RSV seem a good way for the control of respiratory tract diseases.

We assessed the immunogenicity, safety and tolerability of heptavalent pneumococcal conjugate vaccine (PCV7) administered three, five and 11 months post-natally to 46 pre-term (PT) and 46 full-term (FT) infants. After each dose, there was no significant difference between the groups in antibody levels for any of the vaccine serotypes. After the second dose, the majority of subjects in both groups showed titres of ≥0.35μg/mL, whereas an antibody concentration of ≥1.0μg/mL was usually reached in both PT and FT infants after the third dose. Safety and tolerability was also similar in the groups. These findings support the use of the simplified schedule that includes three doses of PCV7 in both PT and FT infants, and suggest that this may reduce costs, as well as problems related to vaccine supply and administration

In order to evaluate the theoretic coverage of the heptavalent conjugate vaccine against community-acquired pneumonia (CAP) during the first years of life, the anti-capsular IgG antibodies to the nine more common pneumococcal serotypes (1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F) were quantitated in 196 affected children aged 2-5 years by means of enzyme-linked immunosorbent assays of acute and convalescent serum samples. Acute Streptococcus pneumoniae infection associated with the nine tested serotypes was diagnosed in 57 children (29.1%). Serological data indicated that 16.8% of CAPs were caused by serotypes included in the heptavalent conjugate vaccine. This study confirms the significant role of S. pneumoniae in pediatric CAP, and highlights the importance of pneumococcal conjugate vaccines in preventing it during the first years of life.

The levels of specific IgG antibody to pneumococcal capsular polysaccharides were investigated in 182 children, aged 2-5 years, who were hospitalized for community-acquired pneumonia, including 55 (30.2%) with evidence of acute pneumococcal infection. Results show that children with concentrations of specific IgG antibody that would protect against invasive disease do not seem to be protected against pneumonia associated with pneumococcal infection.

ABSTRACT Extended-spectrum β-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.

The characteristics of community-acquired pneumonia associated with Streptococcus pneumoniae infection were compared with those associated with atypical bacterial infection and with mixed S. pneumoniae-atypical bacterial infection in 196 children aged 2-5 years. S. pneumoniae infections were diagnosed in 48 patients (24.5%); atypical bacterial infections, in 46 (23.5%); and mixed infections, in 16 (8.2%). Although white blood cell counts and C-reactive protein levels were higher in patients with pneumococcal infections, no other clinical, laboratory, or radiographic characteristic was significantly correlated with the different etiologic diagnoses. There was no significant difference in the efficacy of the different treatment regimens followed by children with S. pneumoniae infection, whereas clinical failure occurred significantly more frequently among children with atypical bacterial or mixed infection who were not treated with a macrolide. This study shows the major role of both S. pneumoniae and atypical bacteria in the development of community-acquired pneumonia in young children, the limited role of clinical, laboratory, and radiological features in predicting etiology, and the importance of the use of adequate antimicrobial agents for treatment.

ABSTRACT A new natural TEM derivative, named TEM-87, was identified in a Proteus mirabilis isolate from an Italian hospital. Compared to TEM-1, TEM-87 contains the following mutations: E104K, R164C, and M182T. Kinetic analysis of TEM-87 revealed extended-spectrum activity against oxyimino cephalosporins (preferentially ceftazidime) and aztreonam. Expression of blaTEM-87 in Escherichia coli decreased the host susceptibility to these drugs.

At our institution, isolation rates of clinical strains of ESBL-producing Proteus mirabilis increased to 8.8% of all P. mirabilis isolates during the period 1997–1999. To evaluate the susceptibility of ESBL-producing P. mirabilis strains against commonly used drugs, we studied 50 non-duplicated isolates selected on the basis of synergy between clavulanate and β-lactams (ceftazidime, aztreonam, cefotaxime, and ceftriaxone). The presence of ESBL-coding genes was confirmed by colony hybridization with blaTEM-1 and blaSHV-1 probes. Minimum inhibitory concentrations of several antimicrobial agents for each isolate were obtained using the Etest method. All strains were encoding for TEM-derived enzymes. Gene sequencing showed that at least three different genes (TEM-15, TEM-20, and TEM-52) were present. These enzymes have not been previously reported in P. mirabilis. Isolates were characterized by: (a) reduced susceptibility or resistance to third- and fourth-generation cephalosporins (MIC≥2 mg/l), (b) resistance to piperacillin that was abolished by tazobactam (MIC≥256 vs. ≤2 mg/l, respectively), (c) multiple antibiotic resistance that included gentamicin, fluoroquinolones and co-trimoxazole. Therapeutic failure and lack of eradication of ESBL-positive P. mirabilis by third-generation cephalosporins has been repeatedly observed both at our Institution and elsewhere. Piperacillin-tazobactam, as well as amikacin and meropenem appear to be important therapeutic options for infections due to multidrug-resistant, ESBL-producing P. mirabilis isolates.

ABSTRACT A new natural TEM-2 derivative, named TEM-72, was identified in aProteus mirabilis strain and in a Morganella morganii strain isolated in Italy in 1999. Compared to TEM-1, TEM-72 contains the following amino acid substitutions: Q39K, M182T, G238S, and E240K. Kinetic analysis showed that TEM-72 exhibits an extended-spectrum activity, including activity against oxyimino-cephalosporins and aztreonam. Expression ofblaTEM-72 in Escherichia coli was capable of decreasing the host susceptibility to the above drugs.

The interaction between tazobactam and several chromosome- and plasmid-encoded (TEM, SHV, PSE types) class A and C beta-lactamases was studied by spectrophotometry. Tazobactam behaved as a competitive inhibitor or inactivator able to restore in several cases the efficiency of piperacillin as a partner beta-lactam. A detailed kinetic analysis permitted measurement of the acylation efficiency for some cephalosporinases and broad-spectrum beta-lactamases; the presence of a turn-over of acyl-enzyme complex was also evaluated.

From May 1996 to September 1997, 615 Pseudomonas aeruginosa strains isolated from patients in intensive care units collected from different Italian laboratories were studied. The susceptibility of piperacillin/tazobactam, in comparison with other antipseudomonal antibiotics, to their NCCLS breakpoints was evaluated: amikacin 79.6%, carbenicillin 67.0%, ceftazidime 73.4%, ciprofloxacin 55.8%, imipenem 64.1%, piperacillin 88.1%, piperacillin/tazobactam 92.4% and ticarcillin/clavulanic acid 69.0%. Seventy-three strains were selected because of their resistance to piperacillin and the mechanisms underlying such a resistance were investigated. Isoelectric focusing and hydrolysis assays revealed the presence of 15 plasmid-mediated β-lactamases. Chromosomal β-lactamase derepression was demonstrated in 34 isolates. The remaining 24 piperacillin-resistant strains did not produce β-lactamases and an ‘intrinsic mechanism’ of resistance was inferred. The piperacillin/tazobactam combination restored resistance in 25 piperacillin strains. Nine of these were derepressed for chromosomal β-lactamase, 8 showed impermeability and 8 showed plasmid enzymes.

From September 1994 to March 1995 an Italian multicenter in vitro study to evaluate the susceptibility of piperacillin/tazobactam compared with that of imipenem, ceftazidime, ceftazidime, ceftriaxone, cefotaxime and ampicillin/sulbactam against aerobic bacterial pathogens isolated in 132 different hospitals, was undertaken. In total, 26,732 isolates were collected but only 25,266 aerobic bacteria were able to be evaluated (16,863 Gram-negative and 8,403 Gram-positive). Escherichia coli was the most frequent pathogen isolated (25.9%) followed by Staphylococcus aureus (14.9%), Pseudomonas aeruginosa (13.9%), Enterococcus faecalis (8.2%) and Klebsiella pneumoniae (5.9%). Piperacillin/tazobactam had a general spectrum of activity (84.8% susceptible strains) comparable to imipenem (87.9%), and was distinctly greater than ceftazidime (71.1%).