Appearance of IMP-1 metallo-β-lactamase in Europe

Cornaglia, Giuseppe; Riccio, Maria Letizia; Mazzariol, Annarita; Lauretti, Laura; Fontana, Roberta; Rossolini, Gian María

doi:10.1016/s0140-6736(98)05954-6

Cited by 131 publications

(74 citation statements)

References 4 publications

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“…In the case of P. aeruginosa, the most frequent mechanism of resistance is loss of the porin OprD (24), but carbapenem-hydrolyzing ␤-lactamases are increasingly reported. They spread first in Japan and Korea and more recently in Europe (4,26,27) and the Americas (7,11). Large outbreaks by MBL-producing P. aeruginosa strains have been described in hospitals in Italy, Greece, and Korea (4,14,16,18,20,29), as well as in Latin America, notably, including one caused by a P. aeruginosa strain with an SPM-1 ␤-lactamase in Brazil (7).…”

Section: Description Of Outbreakmentioning

confidence: 99%

Outbreak of Carbapenem-Resistant Pseudomonas aeruginosa Producing VIM-8, a Novel Metallo-β-Lactamase, in a Tertiary Care Center in Cali, Colombia

Crespo

Woodford²,

Sinclair³

et al. 2004

J Clin Microbiol

143

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The prevalence of imipenem resistance among Pseudomonas aeruginosa isolates at a 195-bed tertiary care medical center in Cali, Colombia, rose from 2% in 1996 to 28% in 1997 and to over 40% in 2003. Many isolates showed high-level multiresistance, and phenotypic characterization suggested the spread of a predominant strain with minor variants. Sixty-six resistant isolates collected between February 1999 and July 2003 from hospitalized patients (n ‫؍‬ 54) and environmental samples (n ‫؍‬ 12) were subjected to a fuller analysis. Genetic fingerprints were compared by pulsed-field gel electrophoresis (PFGE) of SpeI-digested genomic DNA, and bla IMP and bla VIM genes were sought by PCR. PFGE and serotyping indicated that 52 of the 66 isolates belonged to a single strain, with 82% similarity; the PFGE pattern for this organism was designated pattern A. Two further pairs of isolates represented single strains; the remaining nine isolates were unique, and in the case of one isolate, no satisfactory PFGE profile could be obtained. The pattern A isolates were mostly of serotype O12 and were highly resistant to imipenem (MICs, 32 to >256 g/ml), with this resistance decreased eightfold or more in the presence of EDTA. They yielded amplicons with bla VIM -specific primers, and sequencing of DNA from a representative isolate revealed bla VIM-8 , a novel allele with three polymorphisms compared with the sequence of bla VIM-2 . Two of these nucleotide changes were silent, but the third determined a Thr139Ala substitution. Only 4 of 13 resistant isolates (2 clinical isolates and 2 environmental isolates) assigned to other PFGE types carried bla VIM alleles, whereas the others were less multiresistant and mostly had lower levels of imipenem resistance (MICs, <32 g/ml) which was not significantly reduced by EDTA. No bla IMP alleles were detected. During 2003, when the environmental study was undertaken, serotype O12 isolates with bla VIM were recovered from sinks and stethoscopes in the most-affected units, although not from the hands of staff; the problem declined once these reservoirs were disinfected and hygienic precautions were reinforced.

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Section: Description Of Outbreakmentioning

confidence: 99%

Outbreak of Carbapenem-Resistant Pseudomonas aeruginosa Producing VIM-8, a Novel Metallo-β-Lactamase, in a Tertiary Care Center in Cali, Colombia

Crespo

Woodford²,

Sinclair³

et al. 2004

J Clin Microbiol

143

View full text Add to dashboard Cite

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“…The resistance of MDR Acinetobacter spp. to many commonly used antibiotics, such as aminoglycosides, fluoroquinolones, cephalosporins, ␤-lactams, and carbapenems, has been increasingly reported worldwide (7,12,15,22,24). MDR Acinetobacter spp.…”

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Application of a Microsphere-Based Array for Rapid Identification of Acinetobacter spp. with Distinct Antimicrobial Susceptibilities

et al. 2008

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Acinetobacter spp. have emerged as important nosocomial and multidrug-resistant pathogens in the last decade. A. calcoaceticus, A. baumannii, Acinetobacter genospecies 3, and Acinetobacter genospecies 13TU are genetically closely related and are referred to as the A. calcoaceticus-A. baumannii complex (ACB complex). Distinct Acinetobacter spp. may be associated with differences in antimicrobial susceptibility, so it is important to identify Acinetobacter spp. at the species level. We developed a microsphere-based array that combines an allele-specific primer extension assay and microsphere hybridization for the identification of Acinetobacter spp. This assay can discriminate the 13 different Acinetobacter spp. in less than 8.5 h, and it has high specificity without causing cross-reactivity with 14 other common nosocomial bacterial species. The sensitivity of this assay was 100 A. baumannii cells per ml of blood, and it could discriminate multiple species in various mixture ratios. The developed assay could differentiate clinical Acinetobacter spp. isolates with a 90% identification rate. The antimicrobial susceptibility test showed that A. baumannii isolates were resistant to most antimicrobial agents other than imipenem, while the genospecies 3 and 13TU isolates were more susceptible to most antimicrobial agents, especially ciprofloxacin and ampicillinsulbactam. These results supported the idea that this assay possibly could be applied to clinical samples and provide accurate species identification, which might be helpful for clinicians when they are treating infections caused by Acinetobacter spp.

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“…We do not consider these systems further here. In an effort to test this procedure prospectiVely, we also docked 33 000 molecules from the fragment-like subset of the ZINC database (22) against the structure of the zinc -lactamase from Bacteroides fragilis, an antibiotic resistance target for which no inhibitors are available for clinical use (23,24). We experimentally tested several of these predicted, novel molecules for inhibition of the enzyme.…”

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confidence: 99%

Virtual Screening against Metalloenzymes for Inhibitors and Substrates

2005

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Molecular docking uses the three-dimensional structure of a receptor to screen databases of small molecules for potential ligands, often based on energetic complementarity. For many docking scoring functions, which calculate nonbonded interactions, metalloenzymes are challenging because of the partial covalent nature of metal-ligand interactions. To investigate how well molecular docking can identify potential ligands of metalloenzymes using a "standard" scoring function, we have docked the MDL Drug Data Report (MDDR), a functionally annotated database of 95 000 small molecules, against the X-ray crystal structures of five metalloenzymes. These enzymes included three zinc proteases, the nickel analogue of an iron enzyme, and a molybdenum metalloenzyme. The ability of the docking program to retrospectively enrich the annotated ligands as high-scoring hits for each enzyme and to calculate proper geometries was evaluated. In all five systems, the annotated ligands within the MDDR were enriched at least 20 times over random. To test the approach prospectively, a sixth target, the zinc -lactamase from Bacteroides fragilis, was screened against the fragment-like subset of the ZINC database. We purchased and tested 15 compounds from among the top 50 top-ranked ligands from docking, and found 5 inhibitors with apparent K i values less than 120 µM, the best of which was 2 µM. A more ambitious test still was predicting actual substrates for a seventh target, a Zn-dependent phosphotriesterase from Pseudomonas diminuta. Screening the Available Chemicals Directory (ACD) identified 25 thiophosphate esters as potential substrates within the top 100 ranked compounds. Eight of these, all previously uncharacterized for this enzyme, were acquired and tested, and all were confirmed experimentally as substrates. These results suggest that a simple, noncovalent scoring function may be used to identify inhibitors of at least some metalloenzymes.Metalloenzymes are important therapeutic targets, having attracted interest for diseases such as cancer (1, 2), arthritis (3), glaucoma (4), and infectious disease (5), among others. There has been considerable interest in the structural bases for their actions, and the structures of many metalloenzyme targets have been determined. These structures have provided templates for atomic resolution modeling of reaction mechanism and for inhibitor discovery.A problem faced in modeling metalloenzymes is the key role played by the metal. Molecular mechanics potential functions, which underlie most modeling approaches, have been parametrized to treat molecules as interacting either covalently or noncovalently. Metal-ligand interactions fit uncomfortably into either of these categories. Whereas vibrational spectroscopy indicates the presence of a metal ligand bond consistent with a force field treatment, the dative covalent "bond" is nearly an order of magnitude weaker than a covalent bond between first and second row elements. Further complicating the calculations is the unusually high charge ...

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Appearance of IMP-1 metallo-β-lactamase in Europe

Cited by 131 publications

References 4 publications

Outbreak of Carbapenem-Resistant Pseudomonas aeruginosa Producing VIM-8, a Novel Metallo-β-Lactamase, in a Tertiary Care Center in Cali, Colombia

Outbreak of Carbapenem-Resistant Pseudomonas aeruginosa Producing VIM-8, a Novel Metallo-β-Lactamase, in a Tertiary Care Center in Cali, Colombia

Application of a Microsphere-Based Array for Rapid Identification of Acinetobacter spp. with Distinct Antimicrobial Susceptibilities

Virtual Screening against Metalloenzymes for Inhibitors and Substrates

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