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Antimicrob Agents Chemother. 2018 Nov 26;62(12). pii: e00720-18. doi: 10.1128/AAC.00720-18. Print 2018 Dec.

Emergence and Within-Host Genetic Evolution of Methicillin-Resistant Staphylococcus aureus Resistant to Linezolid in a Cystic Fibrosis Patient.

Author information

1
AP-HP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Service de Bactériologie-Hygiène, Clamart, France.
2
EA4043, Bactéries Pathogènes et Santé, Faculté de Pharmacie, Université Paris Sud, Chatenay-Malabry, France.
3
CHU Limoges, Laboratoire de Bactériologie-Virologie-Hygiène, Limoges, France.
4
INSERM, RESINFIT, U 1092, Université Limoges, Limoges, France.
5
Service de Pédiatrie, Centre de Ressource et de Compétence de la Mucoviscidose du Limousin, Hôpital Mère Enfant, Limoges, France.
6
AP-HP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Service de Bactériologie-Hygiène, Clamart, France florence.doucet-populaire@aphp.fr.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infection has increased in recent years among cystic fibrosis (CF) patients. Linezolid (LZD) is one of the antistaphylococcal antibiotics widely used in this context. Although LZD resistance is rare, it has been described as often associated with long-term treatments. Thirteen MRSA strains isolated over 5 years from one CF patient were studied for LZD resistance emergence and subjected to whole-genome sequencing (WGS). Resistance emerged after three 15-day LZD therapeutic regimens over 4 months. It was associated with the mutation of G to T at position 2576 (G2576T) in all 5 rrl copies, along with a very high MIC (>256 mg/liter) and a strong increase in the generation time. Resistant strains isolated during the ensuing LZD therapeutic regimens and until 13 months after LZD stopped harbored only 3 or 4 mutated rrl copies, associated with lower MICs (8 to 32 mg/liter) and low to moderate generation time increases. Despite these differences, whole-genome sequencing allowed us to determine that all isolates, including the susceptible one isolated before LZD treatment, belonged to the same lineage. In conclusion, LZD resistance can emerge rapidly in CF patients and persist without linezolid selective pressure in colonizing MRSA strains belonging to the same lineage.

KEYWORDS:

23S rRNA; MRSA; Staphylococcus aureus ; WGS; cystic fibrosis; linezolid; oxazolidinones; ribosomal resistance

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