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J Antimicrob Chemother. 2015 Nov;70(11):3027-31. doi: 10.1093/jac/dkv217. Epub 2015 Jul 22.

Adaptation to vancomycin pressure of multiresistant Staphylococcus capitis NRCS-A involved in neonatal sepsis.

Author information

1
Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France.
2
Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France.
3
Neonatal Intensive Care Unit, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.
4
Public Health England, Colindale, London, UK.
5
Neonatal Intensive Care Unit, Eastern Hospital Group, Hospices Civils de Lyon, Lyon, France.
6
Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France Laboratory of Bacteriology, Hospices Civils de Lyon, Lyon, France.
7
Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France Laboratory of Bacteriology, Hospices Civils de Lyon, Lyon, France frederic.laurent@univ-lyon1.fr.

Abstract

OBJECTIVES:

The Staphylococcus capitis clone NRCS-A has recently been described as a frequent cause of late-onset sepsis (LOS) in pre-term neonates worldwide. Representatives of this clone exhibit non-susceptibility to vancomycin, the first-line agent used in LOS. Cases of prolonged S. capitis LOS despite vancomycin treatment have been reported. We investigated whether NRCS-A strains exhibit faster adaptation to vancomycin pressure as compared with other staphylococci.

METHODS:

Strains of S. capitis NRCS-A, S. capitis non-NRCS-A and Staphylococcus epidermidis (n = 2 each, all with vancomycin MICs ≤2 mg/L) and the prototype vancomycin-heteroresistant Staphylococcus aureus Mu3 were subcultured daily for 15 days with 0.25-32 mg/L vancomycin. Regression coefficients of daily log2 MICs on time were used to estimate the kinetics of resistance development. Changes in bacterial cell-wall thickness were measured by transmission electron microscopy. To assess the stability of resistance and the emergence of cross-resistance, vancomycin, teicoplanin, daptomycin and linezolid MICs were measured before and after vancomycin treatment, as well as after nine additional subcultures without antibiotics.

RESULTS:

All strains developed a stable resistance to vancomycin, but this occurred significantly faster in S. capitis NRCS-A than in S. capitis non-NRCS-A (P < 0.001) and other species (P < 0.0001). Vancomycin resistance in S. capitis NRCS-A was associated with significant cell-wall thickening and an increase in MICs of daptomycin and teicoplanin, but not linezolid.

CONCLUSIONS:

S. capitis NRCS-A rapidly adapts to vancomycin pressure as compared with potential niche competitors, a feature that might contribute to its success in neonatal ICUs where vancomycin is widely prescribed.

PMID:
26203181
DOI:
10.1093/jac/dkv217
[Indexed for MEDLINE]

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