Dose dependence of emergence of resistance to linezolid in Enterococcus faecalis in vivo

被引:64
作者
Bourgeois-Nicolaos, Nadege
Massias, Laurent
Couson, Brigitte
Butel, Marie-Jose
Andremont, Antoine
Doucet-Populaire, Florence
机构
[1] Hop Bichat Claude Bernard, AP HP, Lab Bacteriol, F-75018 Paris, France
[2] Univ Paris 05, Fac Sci Pharmaceut & Biol, Equipe Acceuil 4065, Paris, France
[3] Univ Paris 07, Equipe Acceuil 3964, F-75221 Paris 05, France
[4] Hop Bichat Claude Bernard, Lab Toxicol, Paris, France
[5] Microbiol Ctr Hosp Versailles, Le Chesnay, France
关键词
D O I
10.1086/513876
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. The emergence of resistance to antibiotics in vivo, particularly in commensal, potentially pathogenic bacteria, is a factor that is key to the future of antibiotics. To better document the circumstances favoring the emergence of resistance to linezolid the first of a new class of antibiotics, the oxazolidinones), we modeled the effect of different regimens of linezolid on Enterococcus faecalis in gnotobiotic mice. Methods. We studied the rate of emergence of linezolid-resistant E. faecalis mutants in the digestive tract of gnotobiotic mice monoassociated with linezolid-susceptible E. faecalis and fed with water containing linezolid (0.5, 0.05, or 0.005 g/L). 23S Ribosomal RNA (rRNA) mutations were characterized by sequencing each of the 4 copies of the rRNA genes individually. Results. Mutants were readily obtained in vivo, but the frequencies, persistence, and type of mutants were all dependent on the linezolid regimen. Mutations conferring resistance, either the G2505A or G2576U mutation, were present in domain V of the 23S rRNA gene of all resistant isolates. Levels of resistance increased with the number of mutated copies of the 23S rRNA gene and with duration of exposure. Conclusion. The antibiotic dose appears to be critical in the dynamics and molecular basis of resistance.
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页码:1480 / 1488
页数:9
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