First report of the activity of linezolid against Portuguese enterococci from human, animal and environmental sources

C. Novais1, J. C. Sousa1, T. M. Coque2, L. V. Peixe1,* and the Resistance Study Group§

1 Lab. Microbiologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; 2 Servicio de Microbiologia, Hospital Universitario Ramón y Cajal, Madrid, Spain

Sir,

Linezolid is the first of a new class of antibiotics, the oxazolidinones, recently licensed for clinical use in Portugal (September 2001). This antibiotic has demonstrated good activity against Gram-positive organisms, including strains resistant to multiple antimicrobials, such as vancomycin-resistant enterococci (VRE). However, the emergence of enterococcal isolates resistant to linezolid has been described recently in areas where VRE rates are high, such as the USA and UK.1,2 Resistance in enterococci may emerge during therapy1 and is spread by cross-infection, although a recent case of enterococcal infection by a resistant strain has been reported in a patient without previous antibiotic exposure.2

To our knowledge, the activity of linezolid against enterococcal isolates with a community origin has not been studied previously. Moreover, there are no data regarding the activity of this antibiotic against enterococcal isolates from Portugal. Our objective was to evaluate the activity of linezolid against Portuguese enterococci isolated from both hospitals and the community, since VRE is commonly recovered not only from the nosocomial setting3 but also from animal and environmental sources4 in this country.

We studied 1127 enterococcal isolates: (i) n = 211 clinical isolates from different patients located at three hospitals in the centre and north of Portugal (1996–2002); (ii) n = 354 from 99 faeces samples of healthy human volunteers living in the centre and north of the country (January–June 2001); (iii) n = 19 from six faeces samples of swine (December 1997–January 1998); (iv) n = 412 from 99 samples of 10 different brands of raw poultry products (93 chicken lots and six turkey lots) collected from two different butcher shops (September 1999–March 2001); (v) n = 131 from 26 samples of sewage water from Porto hospitals obtained just before contact (upstream samples, n = 12) and just after leaving (downstream samples, n = 14) the hospital setting (February 2000–May 2002). Antibiotic susceptibility was determined by an agar dilution method following NCCLS guidelines and using Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as control strains. Isolates were categorized as susceptible or resistant based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Eight hundred and sixty-four isolates were resistant to three or more antibiotics from different groups; 322 were VRE carrying a vanA (72%), vanB (2%) or vanC1 (26%) gene and 119 showed simultaneously high-level resistance to streptomycin and gentamicin. Linezolid showed similar activity against enterococci from distinct sources and species (Table Go). Although the MIC50 was higher than that of other studies (4 versus <2 mg/L),5 the MIC90 was consistent with those reported by other groups. MIC differences among enterococci susceptible and resistant to different antibiotics were not detected (data not shown). This is in agreement with a recent study by Fines & Leclercq6 that demonstrated a lack of cross-resistance between linezolid and other protein synthesis inhibitors, such as macrolides, chloramphenicol, lincosamides, streptogramins and aminoglycosides.


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Table 1. In vitro activity of linezolid against enterococci isolated from different sources
 
Our results indicate that linezolid is a good choice for the treatment of infections caused by multiresistant enterococci in Portugal, an area where the prevalence of VRE in both community and clinical settings is currently high. Since linezolid resistance emerges mainly after courses of treatment with this antibiotic, surveillance of susceptibility before and after using this antibiotic will be necessary in order to prevent the emergence and spread of resistant strains in our area.

Acknowledgements

Linezolid powder was freely provided by Pharmacia Upjohn (Lisbon, Portugal). This study was supported by Fundação Ciência e Tecnologia and Fundo Social Europeu (SFRH/BD/3372/2000 and FCT/POCTI/FEDER 399885/ESP/2001, respectively).

Members of the Resistance Study Group: G. Ribeiro (Hosp. Univ. Coimbra, Portugal), J. M. Ribeiro (Hosp. S. Teotónio, Portugal) and M. H. Ramos (Hosp. Sto António, Portugal).

Footnotes

* Corresponding author. Tel: +351-2-22078946; Fax: +351-2-2003977; E-mail: lpeixe@ff.up.pt Back

§ Members of the Resistance Study Group are listed in the Acknowledgements. Back

References

1 . Auckland, C., Teare, L., Cooke, F., Kaufmann, M. E., Warner, M., Jones, G. et al. (2002). Linezolid-resistant enterococci: report of the first isolates in the United Kingdom. Journal of Antimicrobial Chemotherapy 50, 743–6.[Abstract/Free Full Text]

2 . Jones, R. N., Della-Latta, P., Lee, L. V. & Biedenbach, D. J. (2002). Linezolid-resistant Enterococcus faecium isolated from a patient without previous exposure to an oxazolidinone: report from a SENTRY Antimicrobial Surveillance Program. Diagnostic Microbiology and Infectious Disease 42, 137–9.[CrossRef][ISI][Medline]

3 . European Antimicrobial Resistance Surveillance System. (2001). EARSS Annual Report 2001. [Online]. http://www.earss.rivm.nl/PAGINA/DOC/report2001.pdf (20 November 2002, date last accessed).

4 . Novais, C., Coque, T. M., Sousa, J. C., Ferreira, H. N. & Peixe, L. V. (2002). The community and the environment: insights about recent epidemiology of Enterococcus resistance in Portugal. In Program and Abstracts of the Forty-second Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002. Abstract 1117, p. 101. American Society for Microbiology, Washington, DC, USA.

5 . Henwood, C. J., Livermore, D. M., Johnson, A.P, James D., Warner, M., Gardiner, A. et al. (2000). Susceptibility of Gram-positive cocci from 25 UK hospitals to antimicrobial agents including linezolid. Journal of Antimicrobial Chemotherapy 46, 931–40.[Abstract/Free Full Text]

6 . Fines, M. & Leclercq, R. (2000). Activity of linezolid against Gram positive cocci possessing genes conferring resistance to protein synthesis inhibitors. Journal of Antimicrobial Chemotherapy 45, 797–802.[Abstract/Free Full Text]





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