CMY-13, a Novel Inducible Cephalosporinase Encoded by an<i>Escherichia coli</i>Plasmid

Miriagou, Vivì; Tzouvelekis, L. S.; Villa, Laura; Lebessi, Evangelia; Vatopoulos, A.; Carattoli, Alessandra; Tzelepi, E.

doi:10.1128/aac.48.8.3172-3174.2004

Cited by 47 publications

(40 citation statements)

References 21 publications

(14 reference statements)

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“…For sequencing, primers amplifying the entire bla VIM gene were also used (21). Additionally, PCRs were performed with all of the isolates for the bla IMP MBL gene (18), as well as for the extended-spectrum ␤-lactamase-encoding genes bla TEM , bla CTX-M , and bla SHV-5-type and the AmpC type-encoding gene bla CMY (12,19). Detection and mapping of a class 1 integron were carried out with primers specific for 5Ј and 3Ј conserved segments amplifying the variable region containing the resistance gene cassette (10).…”

Section: Methodsmentioning

confidence: 99%

Outbreak Caused by a Multidrug-Resistant Klebsiella pneumoniae Clone Carrying bla _VIM-12 in a University Hospital

et al. 2008

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, nine nonrepetitive isolates of Klebsiella pneumoniae with reduced susceptibility or resistance to carbapenems were recovered from clinical specimens from separate patients hospitalized in a tertiary care hospital. The imipenem-EDTA synergy test was positive for all isolates. PCR, sequencing, and transferability experiments revealed the novel bla VIM-12 metallo-␤-lactamase gene, which was plasmid mediated and located in a class 1 integron. Pulsed-field gel electrophoresis demonstrated a single macrorestriction pattern, indicating the clonal spread of VIM-12-producing K. pneumoniae.Acquired metallo-␤-lactamases (MBLs) constitute a growing class of ␤-lactamases that readily hydrolyze most ␤-lactam antibiotics, including imipenem and meropenem (20). They are usually embedded in class 1 integron structures carrying various gene cassettes and belong to the group B ␤-lactamases according to the classification scheme proposed by Ambler (1). Five different groups of acquired MBLs have been described (IMP, VIM, SPM, GIM, and SIM enzymes), but the first two of these groups have predominated in gram-negative organisms (8,9,13,20). VIM-type MBLs are commonly encountered among nonfermenters in the Far East and southern Europe (14,15,18,21,22), but during the last few years, the respective bla genes have also spread in members of the family Enterobacteriaceae (11,20,23). Reports of VIM-type MBL-producing K. pneumoniae isolates from Greek hospitals are increasing (5, 7). Recently, a novel VIM-type MBL variant, VIM-12, was identified from a clinical isolate of Klebsiella pneumoniae in Greece (16). In this report, we describe an outbreak caused by K. pneumoniae harboring the bla VIM-12 gene. MATERIALS AND METHODSFrom November 2006 to April 2007, nine nonrepetitive K. pneumoniae isolates exhibiting reduced susceptibility or resistance to imipenem were isolated from clinical specimens collected from separate patients hospitalized in different medical and surgical wards at Hippokration General Hospital, Thessaloniki, Greece. All patients had a long-term hospitalization and had been treated with multiple courses of antimicrobials, including carbapenems. Identification of the isolates to the species level and initial antibiotic susceptibility testing were performed by the Vitek-2 automated system (BioMérieux, Marcy l'Étoile, France), by which they were characterized as imipenem intermediate or resistant.Susceptibilities to a range of antimicrobials (amikacin, amoxicillin-clavulanate, ampicillin, aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, ciprofloxacin, cotrimoxazole, ertapenem, imipenem, meropenem, and tetracycline) were also determined by disk diffusion (3). MICs of imipenem, meropenem, ertapenem, and tigecycline were additionally determined by Etest (AB Biodisk, Solna, Sweden) and the broth microdilution method (3). Susceptibilities were interpreted according to CLSI guidelines (3), when available. For tigecycline, the U.S.FDA (Food and Drug Administration) recommendation was used (susceptible, Յ2 g/ml; resistant, Ն8...

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Section: Methodsmentioning

confidence: 99%

Outbreak Caused by a Multidrug-Resistant Klebsiella pneumoniae Clone Carrying bla _VIM-12 in a University Hospital

et al. 2008

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“…Plasmids carrying genes for AmpC ␤-lactamases often carry multiple other resistances including genes for resistance to aminoglycosides, chloramphenicol, quinolones, sulfonamide, tetracycline, and trimethoprim as well as genes for other ␤-lactamases such as TEM-1, PSE-1 (6), CTX-M-3 (55), SHV varieties (119), and VIM-1 (214). The AmpC gene is usually part of an integron but is not incorporated into a gene cassette with an affiliated 59-base element (273).…”

Section: Plasmid-mediated Ampc ␤-Lactamasesmentioning

confidence: 99%

“…The genes for ACT-1, DHA-1, DHA-2, and CMY-13 are linked to ampR genes and are inducible (16,93,214,274), while other plasmid-mediated AmpC genes are not, including other CMY alleles and apparently CFE-1 despite its linkage to an ampR gene (142,229). Nonetheless, the level of expression of both inducible ACT-1 and noninducible MIR-1 is 33-to 95-fold higher than the level of expression of the chromosomally determined AmpC gene of E. cloacae thanks to a higher gene copy number for the plasmid-determined enzymes (2 copies for bla ACT-1 and 12 copies for bla MIR-1 ) and greater promoter strength for the plasmid genes (8-fold increased from the hybrid MIR-1 promoter and 17-fold increased because of a single base change relative to the wild type in the ACT-1 promoter) (275,276).…”

Section: Plasmid-mediated Ampc ␤-Lactamasesmentioning

confidence: 99%

AmpC β-Lactamases

2009

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SUMMARY AmpC β-lactamases are clinically important cephalosporinases encoded on the chromosomes of many of the Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor-β-lactam combinations. In many bacteria, AmpC enzymes are inducible and can be expressed at high levels by mutation. Overexpression confers resistance to broad-spectrum cephalosporins including cefotaxime, ceftazidime, and ceftriaxone and is a problem especially in infections due to Enterobacter aerogenes and Enterobacter cloacae, where an isolate initially susceptible to these agents may become resistant upon therapy. Transmissible plasmids have acquired genes for AmpC enzymes, which consequently can now appear in bacteria lacking or poorly expressing a chromosomal blaAmpC gene, such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Resistance due to plasmid-mediated AmpC enzymes is less common than extended-spectrum β-lactamase production in most parts of the world but may be both harder to detect and broader in spectrum. AmpC enzymes encoded by both chromosomal and plasmid genes are also evolving to hydrolyze broad-spectrum cephalosporins more efficiently. Techniques to identify AmpC β-lactamase-producing isolates are available but are still evolving and are not yet optimized for the clinical laboratory, which probably now underestimates this resistance mechanism. Carbapenems can usually be used to treat infections due to AmpC-producing bacteria, but carbapenem resistance can arise in some organisms by mutations that reduce influx (outer membrane porin loss) or enhance efflux (efflux pump activation).

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“…One of the problems in clinical practice is the spread of plasmid-mediated AmpC (30). In particular, strains expressing inducible plasmid-mediated AmpC with functional AmpR have been isolated (2,23,24,31). Among those, bla CFE-1 , a plasmid-encoded AmpC that we reported previously, seems to be involved in AmpR-dependent constitutive expression of AmpC (24).…”

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confidence: 99%

Gene Mutations Responsible for Overexpression of AmpC β-Lactamase in Some Clinical Isolates ofEnterobacter cloacae

et al. 2005

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AmpC regulatory genes in 21 ceftazidime-resistant clinical isolates of Enterobacter cloacae (MICs of ≥16 μg/ml) were characterized. All isolates exhibited AmpC overproduction due to AmpD mutation. Additionally, we found two AmpR mutants among the isolates. This is the first report of chromosomal ampR mutation in clinical isolates of E. cloacae .

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CMY-13, a Novel Inducible Cephalosporinase Encoded by anEscherichia coliPlasmid

Cited by 47 publications

References 21 publications

Outbreak Caused by a Multidrug-Resistant Klebsiella pneumoniae Clone Carrying bla _VIM-12 in a University Hospital

Outbreak Caused by a Multidrug-Resistant Klebsiella pneumoniae Clone Carrying bla _VIM-12 in a University Hospital

AmpC β-Lactamases

Gene Mutations Responsible for Overexpression of AmpC β-Lactamase in Some Clinical Isolates ofEnterobacter cloacae

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CMY-13, a Novel Inducible Cephalosporinase Encoded by anEscherichia coliPlasmid

Cited by 47 publications

References 21 publications

Outbreak Caused by a Multidrug-Resistant Klebsiella pneumoniae Clone Carrying bla VIM-12 in a University Hospital

Outbreak Caused by a Multidrug-Resistant Klebsiella pneumoniae Clone Carrying bla VIM-12 in a University Hospital

AmpC β-Lactamases

Gene Mutations Responsible for Overexpression of AmpC β-Lactamase in Some Clinical Isolates ofEnterobacter cloacae

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Outbreak Caused by a Multidrug-Resistant Klebsiella pneumoniae Clone Carrying bla _VIM-12 in a University Hospital

Outbreak Caused by a Multidrug-Resistant Klebsiella pneumoniae Clone Carrying bla _VIM-12 in a University Hospital