Detection of the plasmid-mediated quinolone resistance determinant qnr among clinical isolates of Klebsiella pneumoniae producing AmpC-type  -lactamase

Rodríguez-Martínez, José Manuel; Pascual, Álvaro; Garcı́a, Isabel; Martínez-Martínez, Luis

doi:10.1093/jac/dkg388

Cited by 80 publications

(79 citation statements)

References 12 publications

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“…The armA-carrying IncFIIAs and Inc(unidentified) plasmids and rmtB-carrying IncF plasmid were associated with a relatively high MIC 50 of ciprofloxacin (0.25 mg/liter), suggesting the presence of the plasmid-mediated quinolone resistance determinant qnr. Although the association between qnr determinants and ESBL or pACBL has been demonstrated in previous reports (10,(15)(16)(17), the connection of qnr determinants with armA or rmtB has not yet been determined. In fact, transconjugants that received an Inc(unidentified) plasmid carrying armA showed additional resistance to oxyimino-cephalosporins, such as aztreonam and ceftazidime, suggesting the production of ESBL.…”

Section: Discussionmentioning

confidence: 89%

Distribution of Conjugative-Plasmid-Mediated 16S rRNA Methylase Genes among Amikacin-Resistant Enterobacteriaceae Isolates Collected in 1995 to 1998 and 2001 to 2006 at a University Hospital in South Korea and Identification of Conjugative Plasmids Mediating Dissemination of 16S rRNA Methylase

Kang

Kim

et al. 2008

J Clin Microbiol

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The distribution of conjugative-plasmid-mediated 16S rRNA methylase genes among amikacin-resistant Enterobacteriaceae collected between 1995 and 1998 and between 2001 and 2006 at a university hospital in South Korea was examined, and conjugative plasmids carrying the 16S rRNA methylase genes were characterized by PCR-based replicon typing and by determination of their antimicrobial resistance pattern. Among the 7,127 isolates, 463 isolates showed a high level of resistance to amikacin, and 218 of the 463 isolates transferred amikacin resistance by conjugation. Among the 218 isolates, armA was detected in 153 isolates (88 Klebsiella pneumoniae, 28 Escherichia coli, 19 Enterobacter cloacae, and 6 Serratia marcescens isolates and 12 isolates of other organisms), and rmtB was detected in 51 isolates (32 K. pneumoniae isolates, 18 E. coli isolates, and 1 Citrobacter freundii isolate). The first appearance of armA was in 1997. The armA gene was carried by conjugative plasmids of replicon groups IncL/M, IncFIIAs, IncF, IncA/C, IncHI2, and Inc(unidentified) in 38, 20, 7, 9, 4, and 75 strains, respectively. The rmtB gene was carried by conjugative plasmids of groups IncA/C, IncF, and IncI1-I␥ in 43 strains, 7 strains, and 1 strain, respectively. Transconjugants that received the IncL/M plasmid carrying armA or the IncA/C plasmid carrying rmtB showed an additional resistance to cefotaxime. Transconjugants that received the IncFIIA plasmid or Inc(unidentified) plasmid carrying the armA gene showed an additional resistance to cefoxitin and a high MIC 50 (0.25 mg/liter) of ciprofloxacin. In conclusion, this study demonstrated that the dissemination of 16S rRNA methylase genes among the Enterobacteriaceae is mediated by conjugative plasmids of various incompatibility groups that confer resistance to multiple drugs, including aminoglycosides, extended-spectrum ␤-lactams, and/or quinolones.Aminoglycosides have a high affinity for the 16S rRNA of the bacterial 30S ribosome, and they block protein synthesis (14,20). Over the past few decades, there have been many studies conducted regarding the mechanisms of resistance to aminoglycosides. One of the most common mechanisms of resistance to aminoglycosides is the production of aminoglycoside-modifying enzymes, such as 1-N-aminoglycoside acetyltransferase (AAC), adenyltransferase, and phosphotransferase (14,20). Amikacin was developed to suppress a variety of aminoglycoside-modifying enzymes from their accessing target sites (12), and therefore rare, amikacin-resistant bacteria could be expected. Recently, a series of special methylases that protect microbial 16S rRNA, however, were identified in several nosocomial pathogens, and these enzymes are capable of conferring extraordinarily high levels of resistance (MIC Ͼ 512 mg/liter) to most clinically important aminoglycosides, including amikacin, isepamicin, arbekacin, kanamycin, tobramycin, and gentamicin (5)(6)(7)(8)(21)(22)(23)(24). Since the first identification of a gene encoding 16S rRNA methylase, rmtA, from a Pseudomonas aeru...

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Section: Discussionmentioning

confidence: 89%

Distribution of Conjugative-Plasmid-Mediated 16S rRNA Methylase Genes among Amikacin-Resistant Enterobacteriaceae Isolates Collected in 1995 to 1998 and 2001 to 2006 at a University Hospital in South Korea and Identification of Conjugative Plasmids Mediating Dissemination of 16S rRNA Methylase

Kang

Kim

et al. 2008

J Clin Microbiol

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“…So far, only active efflux of norfloxacin has been reported for E. faecium strain ATCC 19434 (35), but the efflux pump hasn't been identified yet. A novel quinolone resistance mechanism includes a Klebsiella pneumoniae multidrug resistance plasmid-mediated qnr gene that could be transferred horizontally (37) and has ever since been described in clinical isolates of K. pneumoniae in the United States (47,58), E. coli, Citrobacter freundii, and Enterobacter sp. in Europe and China (23,36,59), and Providencia stuartii in Egypt (60).…”

Section: Discussionmentioning

confidence: 99%

High-Level Ciprofloxacin Resistance from Point Mutations in gyrA and parC Confined to Global Hospital-Adapted Clonal Lineage CC17 of Enterococcus faecium

et al. 2006

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To substantiate a common genetic background of ciprofloxacin-resistant Enterococcus faecium, 32 ciprofloxacin-resistant (Cip r ) and 31 ciprofloxacin-susceptible (Cip s ) isolates from outbreaks, clinical infections, surveillances, and animals from 10 different countries were genotyped by multilocus sequence typing. Additionally, susceptibilities to ampicillin and vancomycin and the presence of esp were determined and the quinolone resistance-determining regions of parC, gyrA, parB, and gyrE were sequenced. High-level Cip r (MIC > 64 g/ml) due to point mutations in the quinolone resistance-determining region was unique to a distinct hospital-adapted genetic complex in E. faecium, previously designated CC17. Low-level Cip r (MIC ‫؍‬ 4 g/ml) in non-CC17 strains is not attributable to point mutations in any subunit of the topoisomerase genes, and the mechanism of resistance remains unclear. Acquisition of mutations in parC and gyrA, leading to high-level Cip r , is, in addition to ampicillin resistance and the presence of a putative pathogenicity island, another cumulative step in hospital adaptation of CC17.Over the last two decades, enterococci have become increasingly important as nosocomial pathogens (3). These organisms are intrinsically resistant to a large number of antimicrobials and have the ability to easily acquire new resistance traits (40, 50). The emergence of nosocomial infections caused by ampicillin-, high-level aminoglycoside-, and glycopeptide-resistant Enterococcus faecium has caused clinical concern due to intraand interhospital spread and limited therapeutic options (40, 50). Glycopeptide-resistant enterococci (vancomycin-resistant enterococci [VRE]) are nowadays endemic to the United States, with ϳ30% of enterococcal infections caused by VRE (38, 43); in Europe, the epidemiology of VRE is now changing from a near absence of VRE in hospital-acquired infections at the turn of the century to a situation in which nosocomial epidemics and infections are increasingly reported (3, 13, 17). We recently described a hospital-adapted genetic subtype of E. faecium associated with epidemics and clinical infections, which has spread globally (20,32,62,65). This subpopulation belongs to a distinct genetic lineage labeled clonal complex 17 (CC17) (62) and is associated with the presence of the variant esp gene as part of a pathogenicity island (31) and resistance to ampicillin. Recently, resistance to ciprofloxacin appeared to be associated with ampicillin resistance in genotypically related E. faecium isolates from Norway (25,55,56) and Spain (7).To substantiate a common genetic background of quinoloneresistant E. faecium and association with the hospital-adapted CC17, we studied the genetic relatedness of 32 ciprofloxacinresistant and 31 ciprofloxacin-susceptible E. faecium isolates from various human and animal origins by multilocus sequence typing (MLST) and determined susceptibility to vancomycin and ampicillin and the presence of esp. Finally, we sequenced the quinolone resistance-determining regions (...

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“…Knowledge of the sequence allowed search for qnrA by PCR, and it was soon discovered in a growing number of organisms, including other K. pneumoniae strains in the United States (22,23), Escherichia coli isolates in Shanghai (24), and Salmonella enterica strains in Hong Kong (25). qnrA was subsequently followed by discovery of plasmid-mediated qnrS (26), qnrB (27), qnrC (28), and qnrD (29).…”

Section: Qnr Structure and Functionmentioning

confidence: 99%

“…β-lactamase genes have been conspicuously common, including genes for AmpC β-lactamases (22,(96)(97)(98)(99)(100)(101) 108,127,[132][133][134][135]. qnrB alleles are also frequently found in plasmids linked to variable portions of the operons for psp (phage shock protein) and sap (peptide ABC transporter, ATP-binding protein) genes.…”

Section: Qnr Plasmidsmentioning

confidence: 99%

Plasmid-Mediated Quinolone Resistance

Jacoby

2009

Antimicrobial Drug Resistance

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SummaryThree mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998. Plasmid genes qnrA, qnrB, qnrC, qnrD, qnrS, and qnrVC code for proteins of the pentapeptide repeat family that protects DNA gyrase and topoisomerase IV from quinolone inhibition. The qnr genes appear to have been acquired from chromosomal genes in aquatic bacteria, are usually associated with mobilizing or transposable elements on plasmids, and are often incorporated into sul1-type integrons. The second plasmid-mediated mechanism involves acetylation of quinolones with an appropriate amino nitrogen target by a variant of the common aminoglycoside acetyltransferase AAC(6′)-Ib. The third mechanism is enhanced efflux produced by plasmid genes for pumps QepAB and OqxAB. PMQR has been found in clinical and environmental isolates around the world and appears to be spreading. The plasmid-mediated mechanisms provide only low-level resistance that by itself does not exceed the clinical breakpoint for susceptibility but nonetheless facilitates selection of higher-level resistance and makes infection by pathogens containing PMQR harder to treat.

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Detection of the plasmid-mediated quinolone resistance determinant qnr among clinical isolates of Klebsiella pneumoniae producing AmpC-type -lactamase

Abstract: The qnr determinant is uncommon among clinical isolates of K. pneumoniae and E. coli, but its identification in three pACBL+ K. pneumoniae from the USA indicates the emergence of this quinolone resistance mechanism.

Cited by 80 publications

References 12 publications

Distribution of Conjugative-Plasmid-Mediated 16S rRNA Methylase Genes among Amikacin-Resistant Enterobacteriaceae Isolates Collected in 1995 to 1998 and 2001 to 2006 at a University Hospital in South Korea and Identification of Conjugative Plasmids Mediating Dissemination of 16S rRNA Methylase

Distribution of Conjugative-Plasmid-Mediated 16S rRNA Methylase Genes among Amikacin-Resistant Enterobacteriaceae Isolates Collected in 1995 to 1998 and 2001 to 2006 at a University Hospital in South Korea and Identification of Conjugative Plasmids Mediating Dissemination of 16S rRNA Methylase

High-Level Ciprofloxacin Resistance from Point Mutations in gyrA and parC Confined to Global Hospital-Adapted Clonal Lineage CC17 of Enterococcus faecium

Plasmid-Mediated Quinolone Resistance

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