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Increased frequency of linezolid resistance among clinical Enterococcus faecium isolates from German hospital
Ingo Klare1, Carola Fleige1, Uta Geringer1
1National Reference Centre (NRC) for Staphylococci and Enterococci, Division of Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, Wernigerode Branch, Burgstraße 37, D-38855 Wernigerode, Germany.
Abstract:
Linezolid is an antibiotic of last resort for the treatment of infections with vancomycin-resistant enterococci (VRE). Here we report the increasing prevalence of linezolid resistance among clinical Enterococcus faecium strains from German hospital patients. Linezolid minimum inhibitory concentrations (MICs) were determined for 4461 clinical E. faecium strains isolated between 2008 and 2014. Isolates originated from the network of diagnostic laboratories collaborating with the National Reference Centre (NRC) for Staphylococci and Enterococci covering all German federal states. All linezolid-resistant isolates were determined by broth microdilution and confirmed by Etest as well as by analysing the 23S rDNA for putative mutations. Marker genes were determined by PCR. Genotyping was performed by SmaI macrorestriction analysis in pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) for selected isolates. An increase in linezolid resistance was observed, from <1% in 2008 to >9% in 2014. Occasionally, outbreaks with linezolid-resistant VRE (ST117) were observed. In total, 232 (92.4%) of 251 linezolid-resistant E. faecium isolates (including 61 vanA and 29 vanB) contained the G2576T 23S rDNA mutation and showed a varying mixture of wild-type and mutated alleles per genome sufficient to confer linezolid resistance. In vitro growth experiments revealed a stable linezolid MIC. Of the 251 linezolid-resistant isolates, 5 were cfr-positive. In conclusion, these NRC data identified a country-wide ongoing trend of increasing linezolid resistance among clinical E. faecium isolates within the last 5 years.
Insights
Linezolid resistance in Enterococcus faecium is rising in German hospitals, increasing from less than 1% in 2008 to over 9% in 2014. This trend highlights a growing challenge in treating vancomycin-resistant enterococci infections.
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Linezolid is a critical last-resort antibiotic for treating infections caused by vancomycin-resistant enterococci (VRE).
- Emerging resistance to linezolid poses a significant threat to effective VRE treatment strategies.
Purpose of the Study:
- To investigate the prevalence and trends of linezolid resistance in clinical Enterococcus faecium isolates in Germany.
- To characterize the genetic mechanisms underlying linezolid resistance in these isolates.
Main Methods:
- Analysis of 4461 clinical E. faecium strains collected between 2008 and 2014 from German diagnostic laboratories.
- Determination of linezolid minimum inhibitory concentrations (MICs) using broth microdilution and Etest.
- Genetic analysis including 23S rDNA mutation detection, PCR for marker genes, PFGE, and MLST.
Main Results:
- A significant increase in linezolid resistance was observed, rising from <1% in 2008 to >9% in 2014.
- The G2576T 23S rDNA mutation was identified in 92.4% of resistant isolates, often with a mix of wild-type and mutated alleles.
- Occasional outbreaks of linezolid-resistant VRE (ST117) and five cfr-positive isolates were documented.
Conclusions:
- Country-wide data reveal an ongoing, increasing trend of linezolid resistance in clinical E. faecium isolates in Germany over a five-year period.
- The G2576T mutation is a primary driver of linezolid resistance, with the cfr gene also contributing.
- Continuous surveillance is crucial to monitor and combat the spread of linezolid-resistant VRE.