In vivo emergence of subpopulations expressing teicoplanin or vancomycin resistance phenotypes in a glycopeptide-susceptible, methicillin-resistant strain of Staphylococcus aureus

Vaudaux, Pierre; Francois, Patrice; Berger-Bachi, B.; Lew, Daniel Pablo

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Title		In vivo emergence of subpopulations expressing teicoplanin or vancomycin resistance phenotypes in a glycopeptide-susceptible, methicillin-resistant strain of Staphylococcus aureus
Authors		Vaudaux, Pierre Francois, Patrice Berger-Bachi, B. Lew, Daniel Pablo
Published in		Journal of Antimicrobial Chemotherapy. 2001, vol. 47, no. 2, p. 163-170
Abstract		Several reports indicate the emergence of subpopulations resistant to glycopeptides in some clinical isolates of Staphylococcus aureus. While the development of glycopeptide resistance in S. aureus is easily observed in vitro, the in vivo conditions promoting emergence of glycopeptide-resistant subpopulations are unknown. Using a rat model, subcutaneous implants were chronically infected with a methicillin-resistant strain of S. aureus, MRGR3, devoid of a significant (>10(-7)) glycopeptide-resistant subpopulation at 2 mg/L of either teicoplanin or vancomycin. After 3 weeks of infection in antibiotic-untreated animals, subpopulations emerged, growing on agar containing 10 mg/L of either glycopeptide. These subpopulations were detected in all tissue cage fluids containing >7 log cfu/mL at average frequencies of 4 x 10(-5) and 2 x 10(-5) on teicoplanin- and vancomycin-containing agar, respectively. While teicoplanin MICs increased two- to 16-fold, vancomycin MICs increased by less than two-fold. Population analysis and survival kinetic studies of three teicoplanin-selected subclones indicated that transfer from solid to liquid medium conditions decreased expression of teicoplanin resistance in the bacterial population. In Mueller-Hinton broth, >90% of cells remained fully resistant to antibiotic, but did not grow in the presence of teicoplanin for an initial period of at least 6 h. All three teicoplanin-resistant subclones expressed stable teicoplanin resistance with slight cross-resistance to vancomycin after a few transfers on teicoplanin-supplemented agar. These data suggest that some in vivo conditions may lead to selection of S. aureus subpopulations exhibiting decreased glycopeptide susceptibility and growing in the presence of otherwise inhibitory concentrations of these antimicrobial agents.
Keywords		Anti-Bacterial Agents/ pharmacology — Culture Media — Drug Resistance, Microbial — Humans — Kinetics — Methicillin Resistance/ genetics — Phenotype — Staphylococcus aureus/ drug effects/ genetics/growth & development — Teicoplanin/ pharmacology — Vancomycin Resistance/ genetics
Identifiers		PMID: 11157900
Full text		Article - Limited access to UNIGE Other version: http://jac.oxfordjournals.org/cgi/reprint/47/2/163.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Citation (ISO format)		VAUDAUX, Pierre et al. In vivo emergence of subpopulations expressing teicoplanin or vancomycin resistance phenotypes in a glycopeptide-susceptible, methicillin-resistant strain of Staphylococcus aureus. In: Journal of Antimicrobial Chemotherapy, 2001, vol. 47, n° 2, p. 163-170. https://archive-ouverte.unige.ch/unige:7648