The Italian Epidemiological Survey 1997-1999. Antimicrobial susceptibility data of Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis in Italy.

The Italian Epidemiological Survey began a surveillance study with the aim of monitoring the antimicrobial resistance of respiratory pathogens. From 1997 to 1999, 2028 strains of Haemophilus influenzae and 523 strains of Haemophilus parainfluenzae were collected from 59 Clinical Microbiology Laboratories distributed throughout Italy. In 1998, the study was extended to include Moraxella catarrhalis and a total of 360 isolates were collected. There was a significant increase in the beta-lactamase production both for H. influenzae (from 5% in 1997 to 16% in 1999) and for H. parainfluenzae (from 5% in 1997 to 22% in 1999). Beta-lactamase production in M. catarrhalis was 84% in 1998 and 87% in 1999. Beta-lactamase production affected the susceptibility to unprotected penicillins (87% in H. influenzae, 85% in H. parainfluenzae and 34% in M. catarrhalis), and in part the susceptibility to cefaclor (about 98%). Amoxycillin/clavulanate, cefixime, ceftriaxone and ciprofloxacin were active against all strains of H. influenzae, H. parainfluenzae and M. catarrhalis.

Long-term pertussis-specific immunity after primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine in comparison with that after natural infection.

The aim of this study was to compare pertussis-specific humoral and cellular immunity in children 5 years after a primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine (DTaP-HBV; InfanrixHepB; SmithKline Beecham) with immunity after natural infection. The subjects were 38 children aged 5 to 6 years who received DTaP-HBV at 3, 5, and 11 months of life and 21 subjects of similar ages and sex who acquired pertussis in the first year of life. Immunoglobulin G (IgG) antibody titers against Bordetella pertussis antigens, peripheral blood mononuclear cell-specific proliferation, and the secretion of cytokines were evaluated. After 5 years, only a small proportion of vaccinated and infected children had significant specific concentrations of IgG in serum against all three B. pertussis antigens, and T-cell responses persisted in a minority of subjects. A preferential type 1 cytokine response with the secretion of gamma interferon was observed in the pertussis group, whereas a type 2 skewed response was observed in the vaccinated children; however, the quantitative differences in the cytokines produced by DTaP-HBV and natural infection were minimal. In conclusion, our results show that the immune responses induced by primary pertussis vaccination are qualitatively and quantitatively similar to those seen in children who recovered from natural infection and highlight the need for booster immunization with pertussis vaccines in order to maintain adequate levels of a specific immune response to B. pertussis.

Antimicrobial susceptibility of respiratory isolates of Enterobacteriaceae and Staphylococcus aureus in Italy: incidence and trends over the period 1997-1999.

The antibiotic susceptibility of members of the family Enterobacteriaceae and of Staphylococcus aureus strains isolated from the respiratory tract was assessed over the period 1997-1999 as part of the Italian Epidemiological Observatory survey sponsored by the Smith-Kline Foundation. A standardised method was used to determine the MICs of 22 antibiotics against isolates of Klebsiella pneumoniae (n=870), Escherichia coli (n=684), Enterobacter cloacae (n=342), Enterobacter aerogenes (n=187) and Serratia marcescens (n=135) as well as the MICs of 11 antibiotics against isolates of Staphylococcus aureus (n=1,606). Overall, the susceptibility rate of Enterobacteriaceae isolates was > or = 90% to 5 agents (meropenem, imipenem, amikacin, cefepime and gentamicin); 89-80% to 2 agents (ciprofloxacin and tobramycin); and <80% to 11 agents (cefotaxime, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, cefetamet, ceftriaxone, ceftazidime, aztreonam, ticarcillin-clavulanate, tetracycline, piperacillin, cefuroxime, chloramphenicol, ticarcillin, amoxicillin-clavulanate and amoxicillin). During the 3-year monitoring period, antibiotic susceptibility increased in Klebsiella pneumoniae against amoxicillin-clavulanate, in Escherichia coli against third-generation cephalosporins and aztreonam, in Enterobacter aerogenes against amoxicillin and piperacillin-tazobactam and in Serratia marcescens against most of the antibiotics. In contrast, Enterobacter cloacae showed a tendency to develop resistance to cefetamet, amikacin and ciprofloxacin. Of the total number of Staphylococcus aureus strains, 38% were methicillin resistant. Nearly 80% of the methicillin-resistant strains displayed a multiresistance pattern (additional resistance to 2 or more non-beta-lactam antibiotics). Rates of susceptibility of particular species (Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus) were compared using strains from different geographical areas of Italy (northern, central and southern) and from different nosocomial areas (outpatients, intensive care unit [ICU] inpatients, non-ICU inpatients). Susceptibility of Klebsiella pneumoniae to several antibiotics was lower in southern Italy, whereas the incidence of methicillin-resistant strains was higher in northern and central Italy. The susceptibility of Escherichia coli was similar in all three areas. No significant differences in susceptibility of Klebsiella pneumoniae or Escherichia coli were found between strains from inpatients and outpatients or from inpatients admitted to ICU and non-ICU units. The incidence of methicillin-resistant Staphylococcus aureus was higher in ICU inpatients (52%) than in non-ICU inpatients (38%) and lower in outpatients (19%) than in inpatients.

Chemical reagents as potential impurities of pharmaceutical products: investigations on their genotoxic activity.

The genotoxic activity of chemical reagents and intermediates as potential impurities of final pharmaceutical products have been investigated by the AFI Mutagenesis Study Group. A number of compounds employed in the synthesis of beta-lactam (12), quinolone (6), antiviral (3), and other drugs (11) were analyzed. The information reported in this article was mainly obtained experimentally in our laboratories. In addition, attempts were made to obtain reference data; however, these were available for only a few compounds. The genetic end-point taken into account was principally gene mutation in bacteria. All chemical reagents used in the synthesis of quinolones and antivirals were negative in the Ames test. As far as reagents employed in beta-lactam synthesis were concerned, genotoxic activity was shown by the alkylating agents bromomethanol acetate and chloromethanol acetate, by carbon disulfide, and by the different dimethylanilines. The other chemicals generically considered as involved in "other syntheses" did not induce gene mutation, except for 2,5-dibromopentyl acetate, which was positive in the Ames test. For this compound, as for the halogenated methanol acetates, genotoxic activity was expected in view of its alerting chemical structure.