DNA methylase modifications and other linezolid resistance mutations in coagulase-negative staphylococci in Italy

J Antimicrob Chemother. 2010 Nov;65(11):2336-40. doi: 10.1093/jac/dkq344. Epub 2010 Sep 18.

Abstract

Background: Despite 10 years of clinical use, linezolid resistance in Staphylococcus aureus and coagulase-negative staphylococci (CoNS) is still a rare phenomenon. This study reports the mechanisms of resistance and strain types seen in clusters of linezolid-resistant CoNS from two different hospitals in Italy during the period 2008-09.

Methods: Genes associated with linezolid resistance were subjected to molecular analysis and isolates were characterized by PFGE macrorestriction analysis using SmaI.

Results: Thirty-three linezolid-resistant isolates of methicillin-resistant CoNS comprising Staphylococcus epidermidis (24), Staphylococcus hominis (5) and Staphylococcus simulans (4) were studied. The isolates showed varying levels of linezolid resistance. Almost all isolates for which linezolid MICs were 64 mg/L possessed point mutations in domain V of 23S rRNA, while isolates for which the MICs were 256 mg/L expressed methylase activity at position A2503 mediated by the cfr gene. Overall, the isolates showed reduced susceptibility to vancomycin (MICs 1-2 mg/L) and 11 of the 33 isolates showed no susceptibility to teicoplanin. These strains were also resistant to chloramphenicol (28 of 33), lincomycin (24 of 33), erythromycin (17 of 33) and quinupristin/dalfopristin (13 of 33). S. epidermidis isolates, showing mutations or methylase modifications, belonged to different PFGE profiles and to two different sequence types (ST2 and ST23), in which the cfr gene was carried on a plasmid of ∼50 kb.

Conclusions: Clinical CoNS strains with resistance to linezolid and other second-line antibiotics, as well as reduced susceptibility to glycopeptides, have emerged in Italy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Typing Techniques
  • DNA Fingerprinting
  • DNA Methylation
  • DNA Modification Methylases / metabolism
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Drug Resistance, Multiple, Bacterial*
  • Electrophoresis, Gel, Pulsed-Field
  • Hospitals
  • Humans
  • Italy
  • Linezolid
  • Microbial Sensitivity Tests
  • Oxazolidinones / pharmacology*
  • Point Mutation
  • RNA, Ribosomal, 23S / genetics
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / classification
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / genetics
  • Staphylococcus epidermidis / classification
  • Staphylococcus epidermidis / drug effects*
  • Staphylococcus epidermidis / enzymology
  • Staphylococcus epidermidis / genetics
  • Staphylococcus hominis / classification
  • Staphylococcus hominis / drug effects*
  • Staphylococcus hominis / enzymology
  • Staphylococcus hominis / genetics

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Oxazolidinones
  • RNA, Ribosomal, 23S
  • DNA Modification Methylases
  • CCCGGG-specific type II deoxyribonucleases
  • Deoxyribonucleases, Type II Site-Specific
  • Linezolid