Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 15, Number 1—January 2009
Letter

Linezolid-Resistant Staphylococcus cohnii, Greece

On This Page
Tables
Article Metrics
9
citations of this article
EID Journal Metrics on Scopus

Cite This Article

To the Editor: Since 2003, linezolid has typically been used to treat infections caused by multidrug-resistant gram-positive cocci such as vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus (1). In Greece, a major problem is nosocomial dissemination of vancomycin-resistant enterococci. Use of linezolid for the treatment of such infections led to the emergence of linezolid–vancomycin resistant E. faecium; however, linezolid resistance of staphylococci is still relatively low in this country (2). We describe an outbreak caused by a linezolid-resistant S. cohnii in an intensive care unit (ICU) in Greece.

From July through October 2007, nonrepetitive coagulase-negative staphylococci that exhibited resistance to linezolid were isolated from blood cultures from 4 separate patients hospitalized in the ICU at Sismanoglion General Hospital of Athens, a 450-bed tertiary care hospital. The ICU is a 10-bed, level II unit, comprising 2 rooms with 1 bed each and 2 rooms with 4 beds each. Each isolate was recovered in 2 of 2 blood culture sets per patient, indicating true bacteremia. The demographic and clinical information for the patients is described in the Table. The mean duration of time preceding linezolid therapy was 22 days.

Isolates were first identified to the species level by using an API Staph system (bioMérieux, la Balme les Grottes, France) and a molecular method based on the tuf gene followed by sequencing analysis (3). Susceptibility testing for various antimicrobial agents was performed by disk diffusion and using Clinical Laboratory Standards Institute criteria; susceptibilities were interpreted according to Institute guidelines (4). In addition, MICs to oxacillin, vancomycin, teicoplanin, quinupristin-dalfopristin, linezolid, daptomycin, and tigecycline were determined by Etest (AB Biodisk, Solna, Sweden) according to manufacturer’s instructions. Resistance genes mecA, vat, vga, erm, aac(6´)-Ie+aph(2″), ant(4′)-Ia, and aph(3′)-IIIa, as markers for resistance to β-lactams, dalfopristin, macrolides, and aminoglycosides, were identified by PCR as previously reported (5,6). The presence of G2576T in domain V of the 23S rRNA, which is mainly associated with linezolid resistance in clinical isolates, was detected by using PCR and digestion of the product with NheI (2). The number of mutated versus nonmutated alleles was determined as described by Pillai et al. (7). In addition, isolates were examined for the presence of the cfr gene, which was found to be correlated with linezolid resistance in some coagulase-negative staphylococci and for mutations of ribosomal protein L4, L22 genes (8,9). Clonality of isolates was assessed by pulsed-field gel electrophoresis (PFGE) after digestion of chromosomal DNA with SmaI (2).

The molecular method identified the isolates as S. cohnii subsp. ureolyticus. The API Staph system has correctly identified 2 of them; the remaining 2 isolates were falsely characterized as S. xylosus. According to disc diffusion test results, the isolates were resistant to cefoxitin, oxacillin, penicillin, rifampin, quinupristin-dalfopristin, erythromycin, clindamycin, fusidic acid, tobramycin, gentamicin, and linezolid. MICs were linezolid 32, oxacillin 256, quinupristin-dalfopristin 8, vancomycin 2, teicoplanin 2, tigecycline 0.125, and daptomycin 0.5 mg/L. Molecular methods detected the following resistance genes: mecA, ermA, aac(6´)-Ie+aph(2″), and aph(3´)-IIIa. The isolates, despite their resistance to streptogramins, were negative for vat and vgaA genes. In addition, all isolates carried the G2576T mutation and had 4 of 5 mutated alleles. No isolate carried the cfr gene or any mutation on ribosomal protein L4 and L22 genes. PFGE results indicated that all isolates were clonally related, belonging to the same clone.

Outbreaks caused by linezolid-resistant staphylococci are rare worldwide (10); in Sismanoglion Hospital, before the outbreak period, no linezolid-resistant staphylococci and enterococci had been isolated. However, in the ICU, a statistically significant increase in the use of linezolid was observed in 2004 and in 2007 (0.58 vs. 1.34 defined daily doses/100 patient-days, respectively); heavy use of linezolid may have created substantial selection pressure in favor of the linezolid-resistant isolates.

The 4 patients were treated in the same room by the same personnel; thus, a potential explanation for this outbreak is patient-to-patient transmission of linezolid-resistant strains on the hands of healthcare personnel. However, cultures of ICU personnel (nasal cavity and hands) grew only methicillin-resistant S. aureus and methicilllin-resistant S. epidermidis. In addition, environmental samples taken from the beds and the equipment of these patients were negative for S. cohnii. Strict control measures were taken (e.g., isolation of infected patients, increased environmental cleaning, and reinforcement of proper glove and gown use and hand disinfection with alcohol gel), and the outbreak strain was not recovered from other patients in the ICU or in other departments of the hospital after the initial outbreak. In conclusion, to avoid spread of staphylococcal resistance in ICUs, measures such as hand hygiene and adequate central venous catheter handling should be taken, and policies regarding antimicrobial drug use must be applied.

Top

Efi PetinakiComments to Author , Maria Kanellopoulou, Anthi Damani, Antigoni Foka, Iris Spiliopoulou, Nikoletta Skalmoutsou, Bogdan Raitsiou, Konstantinos Valakis, and Evangelos Papafragas
Author affiliations: University of Thessalia, Larissa, Greece (E. Petinaki); Sismanoglion General Hospital of Athens, Athens, Greece (M. Kanellopoulou, N. Skalmoutsou, B. Raitsiou, K.Valakis, E. Papafragas); Institute of BioMedical Research and Technology, Larissa (E. Petinaki, A. Damani); University of Patras, Patras, Greece (A. Foka, I. Spiliopoulou)

Top

References

  1. Jones  RN, Fritsche  TR, Sader  HS, Ross  JE. LEADER surveillance program results for 2006: an activity and spectrum analysis of linezolid using clinical isolates from the United States (50 medical centers). Diagn Microbiol Infect Dis. 2007;59:30917. DOIPubMedGoogle Scholar
  2. Pratti  A, Karanika  M, Maniatis  AN, Petinaki  E, Spiliopoulou  I, Kolonitsiou  F, Activity of linezolid against gram-positive cocci: a multicentre study in Greek hospitals. Int J Antimicrob Agents. 2007;29:6045. DOIPubMedGoogle Scholar
  3. Kontos  F, Petinaki  E, Spiliopoulou  I, Maniati  M, Maniatis  AN. Evaluation of a novel method based on PCR restriction fragment length polymorphism analysis of the tuf gene for the identification of Staphylococcus species. J Microbiol Methods. 2003;55:4659. DOIPubMedGoogle Scholar
  4. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: CLSI approved standard M100-S16. Wayne (PA): The Institute; 2005.
  5. Lina  G, Quaglia  A, Reverdy  ME, Leclercq  R, Vandenesch  F, Etienne  J. Distribution of genes encoding resistance to macrolides, lincosamides, and streptogramins among staphylococci. Antimicrob Agents Chemother. 1999;43:10626.PubMedGoogle Scholar
  6. Schmitz  FJ, Fluit  AC, Gondolf  M, Beyrau  R, Lindenlauf  E, Verhoef  J, The prevalence of aminoglycoside resistance and corresponding resistance genes in clinical isolates of staphylococci from 19 European hospitals. J Antimicrob Chemother. 1999;43:2539. DOIPubMedGoogle Scholar
  7. Pillai  SK, Sakoulas  G, Wennersten  C, Eliopoulos  GM, Moellering  RC Jr, Ferraro  MJ, Linezolid resistance in Staphylococcus aureus: characterization and stability of resistant phenotype. J Infect Dis. 2002;186:16037. DOIPubMedGoogle Scholar
  8. Mendes  RE, Deshpande  LM, Castanheira  M, DiPersio  J, Saubolle  MA, Jones  RN. First report of cfr-mediated resistance to linezolid in human staphylococcal clinical isolates recovered in the United States. Antimicrob Agents Chemother. 2008;52:22446. DOIPubMedGoogle Scholar
  9. Farrell  DJ, Morrissey  I, Bakker  S, Buckridge  S, Felmingham  D. In vitro activities of telithromycin, linezolid, and quinupristin-dalfopristin against Streptococcus pneumoniae with macrolide resistance due to ribosomal mutations. Antimicrob Agents Chemother. 2004;48:316971. DOIPubMedGoogle Scholar
  10. Kelly  S, Collins  J, Maguire  M, Gowing  C, Flanagan  M, Donnelly  M, An outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit. J Antimicrob Chemother. 2008;61:9017. DOIPubMedGoogle Scholar

Top

Table

Top

Cite This Article

DOI: 10.3201/eid1501.080769

Related Links

Top

Table of Contents – Volume 15, Number 1—January 2009

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.

Top

Comments

Please use the form below to submit correspondence to the authors or contact them at the following address:

Efi Petinaki, Department of Microbiology, University of Thessalia, Medical School Mezourlo, Larissa, Greece;

Send To

10000 character(s) remaining.

Top

Page created: December 06, 2010
Page updated: December 06, 2010
Page reviewed: December 06, 2010
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external