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Biomedical subjects

G Cornaglia

Publications and source records attributed to G Cornaglia.

At least 19 recordsLinked to original sources

Detection of a new SHV-type extended-spectrum beta-lactamase, SHV-31, in a Klebsiella pneumoniae strain causing a large nosocomial outbreak in The Netherlands.

A Klebsiella pneumoniae strain resistant to third-generation cephalosporins was isolated in the eastern Netherlands. The strain was found to carry a novel extended-spectrum beta-lactamase, namely, SHV-31. The combination of the two mutations by which SHV-31 differs from SHV-1, namely, L35Q and E240K, had previously only been described in association with one or more additional mutations.

Anti-Bacterial Agents↗

Antimicrobial susceptibility testing in European hospitals: report from the ARPAC study.

This observational study describes the antimicrobial susceptibility testing (AST) methods and interpretive criteria used in European hospitals during 2001, focusing specifically on detection of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Of 263 hospitals that took part in the ARPAC study, 192 submitted data on AST. Of these, 89% (n = 170) routinely used a disk-diffusion AST method, 43% (n = 82) used a semi-automated method, and 70% (n = 135) routinely determined MICs. Hospitals in southern Europe were less likely to use disk-diffusion, but were more likely to use a semi-automated method (p <0.001). In total, 173 (90%) interpreted AST results using CLSI breakpoints; 30% of these detected MRSA using unmodified CLSI disk-diffusion methods, while 35% used the unmodified CLSI agar-screening method for MRSA; 41% and 30% adhered to unmodified CLSI methodology for disk-diffusion and agar-screening, respectively, to detect VRE. Some of the modifications made may have greatly reduced the ability of the tests to detect MRSA/VRE. For example, 20% of respondents used excessively high incubation temperatures and 13% used inadequate incubation times to detect MRSA by disk-diffusion, and 28% used Mueller-Hinton agar instead of brain-heart infusion agar in VRE screening plates. The majority of respondents stated that they followed CLSI guidelines, but a high proportion had modified the CLSI methods for detecting MRSA and VRE, which may compromise clinical management and antimicrobial resistance surveillance.

Enterococcus↗

European recommendations for antimicrobial resistance surveillance.

The problem of antimicrobial resistance surveillance in Europe has been debated extensively in many excellent documents issued by national committees that often assume the value of national guidelines. However, a comprehensive document addressing the whole matter from a European perspective, as well as reviewing its present status and drafting future perspectives, has been lacking. The present recommendations have been produced by the ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS) through a consensus process involving all members of the Study Group. The recommendations focus on the detection of bacterial resistance and its reporting to clinicians, public health officers and a wider-and ever-increasing-audience. The leading concept is that the basis for resistance monitoring is microbiological diagnostics. The prerequisites for resistance monitoring are findings of adequate quality and quantity, which have been recorded properly and evaluated correctly. Different types of surveillance studies should fulfil different requirements with regard to data collection and reporting, the expected use of data, and the prerequisites for networking such activities. To generate relevant indicators, bacterial resistance data should be reported using adequate denominators and stratification. Reporting of antimicrobial resistance data is necessary for selection of empirical therapy at the local level, for assessing the scale of the resistance problem at the local, national or international levels, for monitoring changes in resistance rates, and for detecting the emergence and spread of new resistances types. Any type of surveillance study should conclude, where appropriate, with a proposal for intervention based on the data obtained.

Anti-Bacterial Agents↗

Report from the European Conference on the Role of Research in Combating Antibiotic Resistance, 2003.

Europe has been at the forefront of efforts to control antibiotic resistance, and this globally important health care problem has prompted numerous recommendations for action at both the national and international levels. Starting in 2002, research on antimicrobial resistance has been considered to be one of the specific objectives of the Sixth Framework Programme (FP6) within the European Union. This report summarises the plenary presentations, as well as the findings of six Working Groups covering specific areas of antibiotic resistance, given at a conference in November 2003 entitled 'The Role of Research in Combating Antibiotic Resistance', co-organised by the European Union and the European Society for Clinical Microbiology and Infectious Diseases, and held in Rome under the patronage of the Italian government.

Anti-Bacterial Agents↗

Comparability of antimicrobial susceptibility test results from 22 European countries and Israel: an external quality assurance exercise of the European Antimicrobial Resistance Surveillance System (EARSS) in collaboration with the United Kingdom National External Quality Assurance Scheme (UK NEQAS).

The goal of this exercise was to organize external quality assurance (QA) of antibiotic susceptibility testing for laboratories participating in EARSS and to assess the comparability of susceptibility test results across countries, and guidelines. In September 2000, UK NEQAS distributed a set of three Streptococcus pneumoniae strains, two Staphylococcus aureus strains and one Streptococcus haemolyticus strain. Laboratories reported the guideline followed, the interpretation of the susceptibility test result and the MIC, if tested. In this study we considered results 'concordant' if the reported interpretation of the participating laboratory agreed with the designated interpretation of reference laboratories. Overall, 433 (92%) of 471 laboratories from 23 countries reported back. Of the 8685 tests that were assessed, 8322 (96%) were interpreted correctly by the participants. Concordance for detection of penicillin non-susceptibility in the three S. pneumoniae strains was 96%, 90% and 87%, respectively. Laboratories performed extremely well in detecting oxacillin resistance in the homogeneously methicillin-resistant S. aureus (MRSA) strain, but the concordance rate dropped from 100% to 77% in the heterogeneously resistant MRSA strain. Concordance for detection of teicoplanin resistance in the S. haemolyticus strain was 82%. We stratified concordance rates first for country and then for guideline used, but observed only minor differences among countries and guidelines. Quantitative methods yielding an MIC were more concordant than non-MIC methods for penicillin resistance in the S. pneumoniae strains (94% versus 79%). The NCCLS guideline was the most frequently followed, by 61% of laboratories from 19 countries. This exercise shows that, overall, countries participating in EARSS are capable of delivering susceptibility data of good quality. The comparability of susceptibility data for penicillin resistance in S. pneumoniae and for homogeneous methicillin resistance in S. aureus is satisfactory among European countries and across guidelines. However, we emphasize the importance of determining an MIC for suspected penicillin non-susceptible S. pneumoniae and for suspected glycopeptide non-susceptible S. aureus. Laboratories, particularly in some countries, may need to improve their capability to detect oxacillin resistance in heterogeneously resistant MRSA. For continuous external quality assessment we recommend that laboratories participate in national and international schemes with frequent distribution of control strains.

Drug Resistance, Bacterial↗

Comparative anti-staphylococcal effects of gemifloxacin and trovafloxacin in an in vitro dynamic model in terms of AUC/MIC and dose relationships.

To compare the antimicrobial effects of gemifloxacin and trovafloxacin on Staphylococcus aureus, their pharmacodynamics were studied in an in vitro dynamic model. A series of pharmacokinetic profiles of gemifloxacin and trovafloxacin with half-lives of 7.4 and 9.2 h, respectively, were simulated in vitro over an eightfold range of area under the curve (AUC)-to-MIC ratio, from 58 to 466 h. The relationships observed between the intensity of antimicrobial effect (I(E)) and log AUC/MIC were linear, species- and strain-independent and were distinct (not superimposed) for both gemifloxacin and trovafloxacin (r(2) = 0.99 in both cases). At AUC/MICs > 100 h, trovafloxacin had greater effects than gemifloxacin. For example, at an AUC/MIC of 250 h, the antimicrobial effect of trovafloxacin was 17% higher than gemifloxacin. However, due to its higher intrinsic activity, gemifloxacin may be as efficient as trovafloxacin at their clinical doses (320 and 200 mg, respectively): the I(E)s on a hypothetical strain of S. aureus with gemifloxacin's and trovafloxacin's MICs corresponding to the MIC(50)s were similar-290 and 310 (log CFU/mL)x h, respectively. This analysis suggests that both AUC/MIC and dose relationships of the antimicrobial effect are needed for comprehensive comparisons of fluoroquinolone pharmacodynamics.

Anti-Infective Agents↗

Surveillance of antimicrobial resistance--what, how and whither?

OBJECTIVE: To express the views of a working party held to consider antibiotic resistance surveillance systems, their strengths and weaknesses, and their current and future applications. METHODS: The participants, all of whom were experienced in this field, discussed the development of surveillance systems in relation to the increasing prevalence of resistance to antibacterial agents and the current interest in surveillance systems shown by many official bodies, in both the human and veterinary fields. The problems inherent in surveillance systems were considered together with the applications of different systems. RESULTS: The properties of good antibiotic resistance surveillance systems were defined. Surveillance systems vary widely from those with a narrow base, focusing on few organisms in one disease area, to those covering many diseases, many organisms (including normal flora) and many compounds. Whatever their design, they should be able to detect significant differences and shifts in susceptibility to various antibacterial agents, and the information derived from them should reach as many interested parties as possible in a timely manner. In using this information to decide strategies, criteria for action need to be determined by pragmatic consensus. Funding remains a major problem, with few large studies being supported by official bodies in spite of their professed enthusiasm for surveillance. In consequence, many current systems are funded by the pharmaceutical industry and are of necessity restricted in their focus. CONCLUSIONS: Antibiotic resistance surveillance studies should and can be well planned and well executed. Many current systems suffer from well-recognized but uncorrected biases. Consortium funding will be necessary for large schemes to be successful. There is no "ideal" surveillance system.

Animals↗

Hospital outbreak of carbapenem-resistant Pseudomonas aeruginosa producing VIM-1, a novel transferable metallo-beta-lactamase.

A total of 8 Pseudomonas aeruginosa isolates was collected from 7 different patients in different wards of the University Hospital of Verona, Italy, from February 1997 to February 1998. The high level of resistance to carbapenems (imipenem minimum inhibitory concentration was always >128 microg/mL) and other broad-spectrum beta-lactams and the rate of imipenem hydrolysis and its inhibition by ethylenediamine-tetra-acetic acid were all suggestive of production of a carbapenem-hydrolyzing metallo-beta-lactamase. A specific DNA probe derived from the recently cloned bla(VIM-1) gene hybridized to all the isolates. A genomic DNA fingerprinting profile revealed clonal relatedness for 7 of 8 isolates. A description of this hospital outbreak is reported, the occurrence of which confirms that proliferation of metallo-beta-lactamase-producing strains multiply resistant to beta-lactams is already a reality outside Japan. These findings emphasize the need for early recognition of similar isolates.

Adult↗

Epidemiological survey of bacterial resistance in upper respiratory tract infections in italy.

The vast majority of infections in the upper airways are caused by four bacterial species;, in Italy as elsewhere, antibiotics resistant strains are emerging. Enzymatic resistance to beta-lactams in Haemophilus influenzae is becoming more important and affects 15% of isolates. On the other hand less than 0.3% of H. influenzae strains are fluoroquinolone-resistant. The number of beta-lactamase-producing Moraxella catarrhalis strains in Italy has been thought to be lower than in other countries, but recent studies suggest 90% of strains are positive, a figure similar to figures reported in the international literature. The most recent data estimate high-level resistance to penicillin in pneumococci to be around 5%, but varies greatly in different geographical areas and with the different origins of the isolates. In spite of the low incidence of penicillin-resistant strains, the most recent figures for macrolide-resistance in Streptococcus pneumoniae range from 26.4 to 31.7%. More than 3 years after the dramatic increase in erythromycin-resistant Streptococcus pyogenes, the resistance levels in Italy are still among the highest in the world. Unlike the experience in other countries, resistance is often related not to the active efflux of antibiotic from the bacterial cell but to ribosomal methylation, thus affecting not only 14- and 15-membered macrolides, but also 16-membered compounds and lincosamides.

Anti-Bacterial Agents↗

Characterization of the metallo-beta-lactamase determinant of Acinetobacter baumannii AC-54/97 reveals the existence of bla(IMP) allelic variants carried by gene cassettes of different phylogeny.

The metallo-beta-lactamase determinant of Acinetobacter baumannii AC-54/97, a clinical isolate from Italy that was previously shown to produce an enzyme related to IMP-1, was isolated by means of a PCR methodology which targets amplification of gene cassette arrays inserted into class 1 integrons. Sequencing revealed that this determinant was an allelic variant (named bla(IMP-2)) of bla(IMP) found in Japanese isolates and that it was divergent from the latter by 12% of its nucleotide sequence, which evidently had been acquired independently. Similar to bla(IMP), bla(IMP-2) was also carried by an integron-borne gene cassette. However, the 59-base element of the bla(IMP-2) cassette was unrelated to those of the bla(IMP) cassettes found in Japanese isolates, indicating a different phylogeny for the gene cassettes carrying the two allelic variants. Expression of the integron-borne bla(IMP-2) gene in Escherichia coli resulted in a significant decrease in susceptibility to a broad array of beta-lactams (ampicillin, carbenicillin, cephalothin, cefoxitin, ceftazidime, cefepime, and carbapenems). The IMP-2 enzyme was purified from an Escherichia coli strain carrying the cloned determinant, and kinetic parameters were determined with several beta-lactam substrates. Compared to IMP-1, the kinetic parameters of IMP-2 were similar overall with some beta-lactam substrates (cefoxitin, ceftazidime, cefepime, and imipenem) but remarkably different with others (ampicillin, carbenicillin, cephaloridine, and meropenem), revealing a functional significance of at least some of the mutations that differentiate the two IMP variants. Present findings suggest that the environmental reservoir of bla(IMP) alleles could be widespread and raise a question about the global risk of their transfer to clinically relevant species.

Acinetobacter↗

Contributions of the AmpC beta-lactamase and the AcrAB multidrug efflux system in intrinsic resistance of Escherichia coli K-12 to beta-lactams.

The roles of the AmpC chromosomal beta-lactamase and the AcrAB efflux system in levels of intrinsic resistance and susceptibility of Escherichia coli to beta-lactams were studied with a set of isogenic strains. MICs of ureidopenicillins, carbenicillin, oxacillin, and cloxacillin were drastically reduced by the inactivation of AcrAB, whereas those of the earlier cephalosporins were affected mostly by the loss of AmpC beta-lactamase.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Molecular typing of erythromycin-resistant streptococcus pyogenes strains with the M phenotype isolated in Italy.

To assess the spread of the new M phenotype, various erythromycin-resistant Streptococcus pyogenes strains from three Italian cities (Verona, Monza, Florence) were characterised. Each strain was analysed for the presence of genes ermAM and mefA, for the ability to accumulate radioactive erythromycin in the absence of sodium arsenate, for the protein T serological type, and for the DNA macrorestriction profile identified by means of pulsed-field gel electrophoresis. In a number of strains, the presence of the inducible ermAM gene was demonstrated; all these strains were negative in the efflux-pump detection assay, did not possess the mefA gene, and had similar restriction profiles. The strains with the efflux mechanism and mefA gene belonged to different serotypes. Of these, only one serotype, T4, was isolated in all three cities. The restriction profile analysis with SmaI and SfiI revealed a very close correlation between strains with the same serotype.

Anti-Bacterial Agents↗