Acquired carbapenemases are emerging resistance determinants in Gram-negative pathogens, including Enterobacteriaceae, Pseudomonas aeruginosa and other Gram-negative non-fermenters. A consistent number of acquired carbapenemases have been identified during the past few years, belonging to either molecular class B (metallo-beta-lactamases) or molecular classes A and D (serine carbapenemases), and genes encoding these enzymes are associated with mobile genetic elements that allow their rapid dissemination in the clinical setting. Therefore, detection and surveillance of carbapenemase-producing organisms have become matters of major importance for the selection of appropriate therapeutic schemes and the implementation of infection control measures. As carbapenemase production cannot be simply inferred from the resistance profile, criteria must be established for which isolates should be suspected and screened for carbapenemase production, and for which tests (phenotypic and/or genotypic) should be adopted for confirmation of the resistance mechanism. Moreover, strategies should be devised for surveillance of carbapenemase producers in order to enable the implementation of effective surveillance programmes. The above issues are addressed in this article, as a follow-up to an expert meeting on acquired carbapenemases that was recently organized by the ESCMID Study Group for Antibiotic Resistance Surveillance.
Although quinolone resistance results mostly from chromosomal mutations, it may also be mediated by a plasmid-encoded qnr gene in members of the family Enterobacteriaceae. Thus, 297 nalidixic-acid resistant strains of 2,700 Escherichia coli strains that had been isolated at the Bicêtre Hospital (Le Kremlin-Bicêtre, France) in 2003 were screened for qnr by PCR. A single E. coli isolate that carried a ca. 180-kb conjugative plasmid encoding a qnr determinant was identified. It conferred low-level resistance to quinolones and was associated with a chromosomal mutation in subunit A of the topoisomerase II gene. The qnr gene was located on a sul1-type class 1 integron just downstream of a conserved region (CR) element (CR1) comprising the Orf513 recombinase. Promoter sequences for qnr expression overlapped the extremity of CR1, indicating the role of CR1 in the expression of antibiotic resistance genes. This integron was different from other qnr-positive sul1-type integrons identified in American and Chinese enterobacterial isolates. In addition, plasmid pQR1 carried another class 1 integron that was identical to In53 from E. coli. The latter integron possessed a series of gene cassettes, including those coding for the extended-spectrum -lactamase VEB-1, the rifampin ADP ribosyltransferase ARR-2, and several aminoglycoside resistance markers. This is the first report of plasmidmediated quinolone resistance in Europe associated with an unknown level of plasmid-mediated multidrug resistance in Enterobacteriaceae.Plasmid-mediated resistance to quinolones was first reported in 1998 in a Klebsiella pneumoniae clinical strain isolated in 1994 in Birmingham, Ala. (10). Plasmid pMG252 of that isolate codes for a 218-amino-acid protein of the pentapeptide repeat family (11) that protects DNA from quinolone binding (21). This Qnr determinant confers resistance to nalidixic acid and increases the MICs of fluoroquinolones by four-to eightfold (10,21,23).Then, qnr-like genes were identified in conjugative plasmids that varied in size from 54 to Ͼ180 kb in Escherichia coli and K. pneumoniae isolates in Shanghai, China, and the United States, respectively (19,(21)(22)(23)(24). No qnr-like genes have been identified from other parts of the world, including Europe (5, 19). The qnr gene has been identified in complex In4 family class 1 integrons (21, 24), known as complex sul1-type integrons. Sul1-type integrons possess duplicated qacE⌬1 and sul1 genes that surround a sequence (usually orf513) that may act as a recombinase for mobilization of the antibiotic resistance genes located nearby (e.g., qnr, bla CTX-M , and ampC). The qnr gene is not associated with the 59-bp element, although common integron-associated resistance genes are (15). The definition of the conserved region (CR) established recently indicates that it consists of an orf513 gene that encodes a recombinase and a right-hand boundary that may act as a recombination crossover site (15).Several -lactamase genes are associated with qnr-positive plasmids, such as those co...
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