Increased frequency of linezolid resistance among clinical Enterococcus faecium isolates from German hospital patients

Klare, Ingo; Fleige, Carola; Geringer, Uta; Thürmer, Alexander; Bender, Jennifer K.; Mutters, Nico T.; Mischnik, Alexander; Werner, Guido

doi:10.1016/j.jgar.2015.02.007

Cited by 53 publications

(35 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While in systematic surveillance a stable low prevalence of linezolid resistance in Gram-positive bacteria, including enterococci, is observed [7], some other studies show a local increase of LRE, e.g. in Germany [31], similar to the situation observed in Poland. In our study, over 70% of LRE were isolated from patients of intensive care units (ICUs) and haematology wards, which are wards with the highest use of antimicrobials, including linezolid.…”

Section: Discussionmentioning

confidence: 97%

Linezolid-resistant enterococci in Polish hospitals: species, clonality and determinants of linezolid resistance

Gawryszewska

Żabicka

Hryniewicz

et al. 2017

Eur J Clin Microbiol Infect Dis

View full text Add to dashboard Cite

The significant increase of the linezolid-resistant enterococci (LRE) has been observed in Polish hospitals since 2012 and our study aimed at elucidating the possible reasons for this phenomenon. Polish LRE isolates were analysed by multilocus-sequence typing (MLST) and multiple locus variable-number tandem repeat (VNTR) analysis (MLVA), polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) to establish clonal relatedness and mechanism of linezolid resistance, respectively. Fifty analysed LRE (2008–2015) included mostly Enterococcus faecium (82%) and Enterococcus faecalis (16%). Enterococcus faecium belonged to the hospital-adapted lineages 17/18 and 78, while E. faecalis isolates represented ST6, a hospital-associated type, and ST116, found in both humans and food-production animals. The G2576T 23S rRNA mutation was the most frequent (94%) mechanism of linezolid/tedizolid resistance of LRE. None of the isolates carried the plasmid-associated gene of Cfr methyltransferase, whereas optrA, encoding the ABC-type drug transporter, was identified in two E. faecalis isolates. In these isolates, optrA was located on a plasmid, transferable to both E. faecium and E. faecalis, whose partial (36.3 kb) sequence was 100% identical to the pE394 plasmid, identified previously in China in both clinical and farm animal isolates. The optrA–E. faecium transconjugant displayed a significant growth deficiency, in contrast to the optrA–E. faecalis. Our study indicates the role of mutation acquisition by hospital-adapted clones of enterococci as a major driver of increasing resistance to linezolid and tedizolid. Transferability and apparent lack of a biological cost of resistance suggest that E. faecalis may be a natural reservoir of optrA, an emerging mechanism of oxazolidinone resistance.Electronic supplementary materialThe online version of this article (doi:10.1007/s10096-017-2934-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 97%

Linezolid-resistant enterococci in Polish hospitals: species, clonality and determinants of linezolid resistance

Gawryszewska

Żabicka

Hryniewicz

et al. 2017

Eur J Clin Microbiol Infect Dis

View full text Add to dashboard Cite

show abstract

“…Five clinical LRE isolates, collected between 2013 and 2015 from German hospital patients, were tested positive in cfr -specific PCR screening experiments [3]. The strains exhibited a multidrug-resistant phenotype with varying levels of MICs to linezolid ranging from 6 mg/L to 48 mg/L (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…We herein describe the detailed investigation of the first cfr(B) variant - containing E . faecium strains isolated from German hospital patients [3]. Cfr and recently cfr(B) have already been shown to be distributed across various bacterial species [16, 22, 37] and outbreaks involving cfr -encoding Gram-positive bacteria haven been reported [38].…”

Section: Discussionmentioning

confidence: 99%

“…faecium strains isolated from German hospital patients and exhibiting linezolid resistance (Table 1) were tested positive for cfr by PCR as described previously [3, 23]. Two closely related C .…”

Section: Methodsmentioning

confidence: 99%

“…After the approval of linezolid in 2000, emergence of resistant strains upon linezolid therapy has been reported for both VRE and vancomycin-susceptible enterococci (VSE) [1, 2]. Although linezolid-resistant enterococci (LRE) are generally detected at low prevalence in Europe, the National Reference Centre (NRC) for Staphylococci and Enterococci at the Robert Koch Institute recognized an increasing number of LRE in German hospitals [3]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Detection of a cfr(B) Variant in German Enterococcus faecium Clinical Isolates and the Impact on Linezolid Resistance in Enterococcus spp.

et al. 2016

Self Cite

View full text Add to dashboard Cite

The National Reference Centre for Staphylococci and Enterococci in Germany has received an increasing number of clinical linezolid-resistant E. faecium isolates in recent years. Five isolates harbored a cfr(B) variant gene locus the product of which is capable of conferring linezolid resistance. The cfr(B)-like methyltransferase gene was also detected in Clostridium difficile. Antimicrobial susceptibility was determined for cfr(B)-positive and linezolid-resistant E. faecium isolates and two isogenic C. difficile strains. All strains were subjected to whole genome sequencing and analyzed with respect to mutations in the 23S rDNA, rplC, rplD and rplV genes and integration sites of the cfr(B) variant locus. To evaluate methyltransferase function, the cfr(B) variant of Enterococcus and Clostridium was expressed in both E. coli and Enterococcus spp. Ribosomal target site mutations were detected in E. faecium strains but absent in clostridia. Sequencing revealed 99.9% identity between cfr(B) of Enterococcus and cfr of Clostridium. The methyltransferase gene is encoded by transposon Tn6218 which was present in C. difficile Ox3196, truncated in some E. faecium and absent in C. difficile Ox3206. The latter finding explains the lack of linezolid and chloramphenicol resistance in C. difficile Ox3206 and demonstrates for the first time a direct correlation of elevated linezolid MICs in C. difficile upon cfr acquisition. Tn6218 insertion sites revealed novel target loci for integration, both within the bacterial chromosome and as an integral part of plasmids. Importantly, the very first plasmid-association of a cfr(B) variant was observed. Although we failed to measure cfr(B)-mediated resistance in transformed laboratory strains the occurrence of the multidrug resistance gene cfr on putatively highly mobile and/or extrachromosomal DNA in clinical isolates is worrisome with respect to dissemination of antibiotic resistances.

show abstract

Multidrug‐resistant Enterococcus faecium strains enter the Norwegian marine environment through treated sewage

Radisic,

Grevskott,

Junghardt

et al. 2024

MicrobiologyOpen

View full text Add to dashboard Cite

This study aimed to understand the antibiotic resistance prevalence among Enterococcus spp. from raw and treated sewage in Bergen city, Norway. In total, 517 Enterococcus spp. isolates were obtained from raw and treated sewage from five sewage treatment plants (STPs) over three sampling occasions, with Enterococcus faecium as the most prevalent (n = 492) species. E. faecium strains (n = 307) obtained from the influent samples, showed the highest resistance against quinupristin/dalfopristin (67.8%). We observed reduced susceptibility to erythromycin (30.6%) and tetracycline (6.2%) in these strains. E. faecium strains (n = 185) obtained from the effluent samples showed highest resistance against quinupristin/dalfopristin (68.1%) and reduced susceptibility to erythromycin (24.9%) and tetracycline (8.6%). We did not detect resistance against last‐resort antibiotics, such as linezolid, vancomycin, and tigecycline in any of the strains. Multidrug‐resistant (MDR) E. faecium strains were detected in both influent (2.3%) and effluent (2.2%) samples. Whole genome sequencing of the Enterococcus spp. strains (n = 25) showed the presence of several antibiotic resistance genes, conferring resistance against aminoglycosides, tetracyclines, and macrolides, as well as several virulence genes and plasmid replicons. Two sequenced MDR strains from the effluents belonged to the hospital‐associated clonal complex 17 and carried multiple virulence genes. Our study demonstrates that clinically relevant MDR Enterococcus spp. strains are entering the marine environment through treated sewage.

show abstract

Increased frequency of linezolid resistance among clinical Enterococcus faecium isolates from German hospital patients

Cited by 53 publications

References 18 publications

Linezolid-resistant enterococci in Polish hospitals: species, clonality and determinants of linezolid resistance

Linezolid-resistant enterococci in Polish hospitals: species, clonality and determinants of linezolid resistance

Detection of a cfr(B) Variant in German Enterococcus faecium Clinical Isolates and the Impact on Linezolid Resistance in Enterococcus spp.

Multidrug‐resistant Enterococcus faecium strains enter the Norwegian marine environment through treated sewage

Contact Info

Product

Resources

About