JAC Advance Access originally published online on January 8, 2008
Journal of Antimicrobial Chemotherapy 2008 61(3):515-523; doi:10.1093/jac/dkm508
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Original research |
Linkage of acquired quinolone resistance (qnrS1) and metallo-β-lactamase (blaVIM-1) genes in multiple species of Enterobacteriaceae from Bolzano, Italy
1 Laboratorio Interaziendale di Microbiologia e Virologia, Via Amba Alagi 5, I-39100 Bolzano, Italy 2 Antibiotic Resistance Monitoring and Reference Laboratory, Health Protection Agency, Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK
Received 12 October 2007; returned 30 November 2007; revised 24 November 2007; accepted 2 December 2007
* Corresponding author. Tel: +44-20-8327-7255; Fax: +44-20-8327-6264; E-mail: neil.woodford{at}hpa.org.uk
Objectives: Twenty-four of 209 oxyimino-cephalosporin- and/or aztreonam-resistant Enterobacteriaceae collected around Bolzano had reduced susceptibility or resistance to carbapenems and gave positive metallo-β-lactamase (MBL) tests. Their resistance mechanisms were investigated.
Methods: Resistances were identified by Vitek 2 and MIC tests and isolates were genotyped by PFGE. Resistance genes were identified by PCR and sequencing, and plasmids were transferred by conjugation and/or transformation. Plasmid-borne genes were identified by Southern blotting, and their genetic surroundings were investigated by PCR mapping.
Results: The 24 isolates with positive EDTA/imipenem synergy tests had blaVIM-1 carried on 40–150 kb plasmids. Imipenem MICs ranged from 2 to >32 mg/L, while those of meropenem and ertapenem were lower. The isolates included a clonal cluster of 10 Klebsiella pneumoniae, two other K. pneumoniae isolates, and diverse isolates of Escherichia coli (seven), Klebsiella oxytoca (three) and Citrobacter freundii (two). Six MBL producers were aztreonam-susceptible; the 18 aztreonam-resistant isolates had co-resident extended-spectrum β-lactamases. blaVIM-1 occurred as the first cassette in class 1 integrons, with aacA4 as the second cassette. Quinolone resistance gene qnrS1 was detected in 21 of 24 (87.5%) blaVIM-1-positive isolates versus 14 of 185 (7.6%) blaVIM-negative isolates (P < 0.0001), with 13 of the latter belonging to a clonal cluster of E. coli. qnrS1 was located on the same plasmids as blaVIM-1 and aacA4, but was not closely linked, as judged by PCR mapping.
Conclusions: blaVIM-1 has become disseminated among enterobacteria in a small Italian town. The frequent association of genes conferring carbapenem, aminoglycoside and quinolone resistance on single plasmids will facilitate co-selection.
Keywords: carbapenemases , plasmids , DNA gyrase , fluoroquinolones
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