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

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Butin, Marine | Martins-Simões, Patricia | Picaud, J. C. | Kearns, A. | Claris, O. | Vandenesch, François | Laurent, Frédéric | Rasigade, Jean-Philippe

Edité par CCSD ; Oxford University Press (OUP) -

International audience. 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?\textless?0.001) and other species (P?\textless?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.

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