Molecular characterization of Norwegian clinical isolates of Escherichia coli hyperproducing the chromosomal AmpC beta-lactamase : a regional spread of an IS911-mediated blaAmpC-hyperexpressing ST131 clone
AuthorRamberg, Cathrine Caspersen
The worldwide dissemination of antimicrobial resistance is a growing problem causing increased morbidity, mortality, and financial costs. β-lactams are an important family of antimicrobial agents and accounts for ~46% of the total antibiotic use for systemic infections in Norway. Resistance to β-lactams can be caused by several factors where the production of enzymes, β-lactamases, is the major mechanism. Escherichia coli naturally produce small amounts of the chromosomally encoded AmpC β-lactamase. The expression blaAmpC is noninducible and regulated by a weak promoter and an attenuator. Insertion sequence (IS) elements inserted into the promoter region have been described as one reason for the hyperexpression of blaAmpC conferring resistance to β-lactams such as penicillins and cephalosporins, but not 4th generation cephalosporins and carbapenems. In this study 111 E. coli isolates with a hyperexpressed chromosomal AmpC profile were submitted to the Reference Center for Detection of Antimicrobial Resistance (K-res) from Haukeland University Hospital during 2006-2010 and a control group representing the same years from other Norwegian clinical microbiological laboratories (n=100) were included. The isolates were initially screened for an insertion of an element in the blaAmpC. A subset of isolates with an insertion was further molecularly characterized by sequencing of the region and linkage to IS911. Molecular typing was performed using multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Multi-resistance profiles were identified by antimicrobial susceptibility testing and further investigated by PCR and sequencing methods. The results from the study shows a regional clonal spread of ST131 E. coli blaAmpC-IS911 isolates in the Bergen region of Norway. The spread of these isolates were identified both in isolates from Hospital 1 and 2 but also from other medical institutions such as nursing homes and general practitioners. In contrast, no isolates from the control group from other Norwegian hospitals harbored the blaAmpC-IS911 linkage. In the control group only three isolates from two Norwegian counties, Vestfold and Rogaland were identified with an insertion in the blaAmpC region. However, in these isolates another IS-element, IS10 was identified. In the ST131 isolates multi-resistance was observed towards important antibiotics such as ciprofloxacin, gentamicin, tobramycin, and trimethoprim-sulphamethoxazole. Resistance to ciprofloxacin was caused by mutations in the quinolone-resistance determining region of the parC and gyrA genes. The resistance mechanism to the aminoglycosides gentamicin and tobramycin were not identified, but the isolates were negative for the aminoglycoside modifying enzyme AAC(6’)-Ib.
PublisherUniversitetet i Tromsø
University of Tromsø
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