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Antimicrobial Agents and Chemotherapy, May 2007, p. 1661-1665, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.00744-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Single-Dose Oral Amoxicillin or Linezolid for Prophylaxis of Experimental Endocarditis Due to Vancomycin-Susceptible and Vancomycin-Resistant Enterococcus faecalis{triangledown}

Philippe Moreillon,1 Walter R. Wilson,2 Roland Leclercq,3 and José M. Entenza1*

Department of Fundamental Microbiology, University of Lausanne, 1015 Lausanne, Switzerland,1 Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905,2 Service de Microbiologie, Centre Hospitalier Universitaire, 14033 Caen, France3

Received 19 June 2006/ Returned for modification 25 October 2006/ Accepted 28 February 2007

Endocarditis prophylaxis following genitourinary or gastrointestinal procedures targets Enterococcus faecalis. Prophylaxis recommendations advocate oral amoxicillin (2 g in the United States and 3 g in the United Kingdom) in moderate-risk patients and intravenous amoxicillin (2 g) or vancomycin (1 g) plus gentamicin in high-risk patients. While ampicillin-resistant (or amoxicillin-resistant) E. faecalis is still rare, there is a concern that these regimens might fail against vancomycin-resistant and/or aminoglycoside-resistant isolates. The present study tested oral linezolid as an alternative. Rats with catheter-induced aortic vegetations were given prophylaxis simulating human pharmacokinetics of oral amoxicillin (2- to 3-g single dose), oral linezolid (600 mg, single or multiple oral doses every 12 h), or intravenous vancomycin (1-g single dose). Rats were then inoculated with the minimum inoculum infecting 90% of the animals (90% infective dose [ID90]) or with 10 times the ID90 of the vancomycin-susceptible E. faecalis strain JH2-2 or the vancomycin-resistant (VanA phenotype) E. faecalis strain UCN41. Amoxicillin was also tested with two additional vancomycin-susceptible E. faecalis strains, 309 and 1209. Animals were sacrificed 3 days later. All the tested bacteria were susceptible to amoxicillin and gentamicin. Single-dose amoxicillin provided 100% protection against all four isolates at both the ID90 and 10 times the ID90. In contrast, linezolid required up to four consecutive doses to provide full protection against the vancomycin-resistant isolate. Vancomycin protected only against the vancomycin-susceptible strain. The high efficacy of single-dose oral amoxicillin suggests that this regimen could be used for prophylaxis in both moderate-risk and high-risk patients without additional aminoglycosides. Linezolid appears to be less reliable, at least against the vancomycin-resistant strain.

* Corresponding author. Mailing address: Department of Fundamental Microbiology, Biophore Building, University of Lausanne, CH-1015 Lausanne, Switzerland. Phone: 41-21-6925613. Fax: 41-21-6925605. E-mail: jose.entenza{at}unil.ch

{triangledown} Published ahead of print on 12 March 2007.

Antimicrobial Agents and Chemotherapy, May 2007, p. 1661-1665, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.00744-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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