Increased high-level gentamicin resistance in invasive Enterococcus faecium is associated with aac(6')Ie-aph(2″)Ia-encoding transferable megaplasmids hosted by major hospital-adapted lineages.
Gentamicin is important in synergistic bactericidal therapy with cell wall agents for severe enterococcal infections. During 2003-2008, a 10-fold increase in the prevalence of high-level gentamicin resistance (HLGR), to above 50%, in blood culture isolates of Enterococcus faecium, was reported by the Norwegian Surveillance System for Antimicrobial Resistance. A representative national collection of invasive E. faecium isolates (n = 99) from 2008 was examined by a multilevel approach. Genotyping revealed a polyclonal population dominated by major hospital-associated lineages (mainly ST203, ST17, ST18, ST202 and ST192). The presence of aac(6')-Ie-aph(2″)-Ia, encoding the bi-functional aminoglycoside-modifying enzyme, was found in 98% of HLGR isolates (56/57). Furthermore, a significantly higher prevalence of potential virulence genes, toxin-antitoxin loci as well as pRE25 and pRUM type replicons was demonstrated in isolates belonging to major hospital-associated lineages compared to other sequence types. Megaplasmids of pLG1 replicon type (200-330 kb) were present in 90% of the isolates. Co-hybridization analyses revealed genetic linkage of aac(6')-Ie-aph(2″)-Ia to this replicon type. Transfer of HLGR-encoding plasmids was restricted to E. faecium. In conclusion, the increased prevalence of HLGR in invasive E. faecium in Norway is associated with hospital-adapted genetic lineages carrying aac(6')-Ie-aph(2″)-Ia-encoding transferable megaplasmids of the pLG1 replicon type.
Research Group for Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
Torill C S
TC
Rosvoll
Belinda L
BL
Lindstad
Tracy M
TM
Lunde
Kristin
K
Hegstad
Bettina
B
Aasnaes
Anette M
AM
Hammerum
Camilla H
CH
Lester
Gunnar S
GS
Simonsen
Arnfinn
A
Sundsfjord
Torunn
T
Pedersen
D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D003428:Cross Infection / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D016984:Enterococcus faecium / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D005838:Genotype; D005839:Gentamicins / Q000378:metabolism / Q000494:pharmacology*; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006761:Hospitals; D006801:Humans; D058889:Molecular Typing; D009664:Norway; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids
D000900:Anti-Bacterial Agents; D005839:Gentamicins; C108453:6'-aminoglycoside acetyltransferase-2''-aminoglycoside phosphotransferase; D000123:Acetyltransferases; D017853:Phosphotransferases (Alcohol Group Acceptor)