title: Susceptibility trends including emergence of linezolid resistance among coagulase-negative staphylococci and meticillin-resistant Staphylococcus aureus from invasive infections.
abstract: Multiresistance in staphylococci constitutes a major challenge for the antimicrobial chemotherapy of invasive infections such as bacteraemia or bone and joint infections (BJIs). A nationwide prospective study was performed to detect antimicrobial resistance trends among staphylococci causing invasive infections. Between October 2011 and February 2012, 367 meticillin-resistant Staphylococcus aureus (MRSA) and 695 coagulase-negative staphylococci (CoNS) were collected from 37 French hospitals, mainly from bacteraemia (59.9%) and osteoarticular infections (29.0%). Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and specific screening and confirmation tests were performed to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Staphylococcal isolates exhibiting a linezolid MIC>4 mg/L were further characterised to determinate their clonal relationships and the mechanism of resistance. MRSA exhibited additional resistances, including levofloxacin (82% associated resistance), gentamicin (13.6%), fusidic acid (13.6%) and rifampicin (6.5%), compromising oral step-down therapy in BJIs. Only two hVISA strains (0.5%) were identified. Among the CoNS, mainly Staphylococcus epidermidis (506/695; 72.8%), resistance to first- and second-line agents was more common. Linezolid resistance was identified in 10 CoNS (1.4%). The most frequent linezolid resistance mechanism was the G2576T mutation in 23S rDNA (9/10). For the first time in France, the cfr gene was found in five related sequence type 2 (ST2) S. epidermidis from two different hospitals, in association with ribosomal RNA and L3 ribosomal protein mutations. These national data must be considered when selecting empirical treatment for invasive staphylococcal infections. Moreover, the emergence and spread of linezolid-resistant CoNS carrying the cfr gene is of concern.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Béclère, Service de bactériologie-hygiène, HUPS, 92140 Clamart, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Henri Mondor, Département de microbiologie, 94000 Créteil, France. Electronic address: jean-winoc.decousser@hmn.aphp.fr.
authors.forename: Jean-Winoc
authors.initials: JW
authors.lastname: Decousser
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Béclère, Service de bactériologie-hygiène, HUPS, 92140 Clamart, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Henri Mondor, Département de microbiologie, 94000 Créteil, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Desroches
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Béclère, Service de bactériologie-hygiène, HUPS, 92140 Clamart, France; EA 4043, USC INRA, Université Paris-Sud, 92290 Châtenay-Malabry, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Bourgeois-Nicolaos
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Béclère, Service de bactériologie-hygiène, HUPS, 92140 Clamart, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Potier
authors.affiliation: Institut de Bactériologie, Faculté de médecine, Université Louis Pasteur l, 67000 Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Jehl
authors.affiliation: International Center for Infectiology Research (CIRI), INSERM, U1111, École normale supérieure de Lyon, Université Lyon 1, CNRS, UMR5308, Lyon, France; Centre national de référence des Staphylocoques, Hospices Civils de Lyon, 69500 Bron, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lina
authors.affiliation: Département de microbiologie, CHR Caen, 14000 Caen, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cattoir
authors.affiliation: International Center for Infectiology Research (CIRI), INSERM, U1111, École normale supérieure de Lyon, Université Lyon 1, CNRS, UMR5308, Lyon, France; Centre national de référence des Staphylocoques, Hospices Civils de Lyon, 69500 Bron, France.
authors.forename: François
authors.initials: F
authors.lastname: Vandenesh
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Béclère, Service de bactériologie-hygiène, HUPS, 92140 Clamart, France; EA 4043, USC INRA, Université Paris-Sud, 92290 Châtenay-Malabry, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Doucet-Populaire
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D003030:Coagulase / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005602:France; D005672:Fusidic Acid / Q000494:pharmacology; D005839:Gentamicins / Q000494:pharmacology; D006761:Hospitals; D006801:Humans; D064704:Levofloxacin / Q000494:pharmacology; D000069349:Linezolid / Q000494:pharmacology*; D008712:Methicillin / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C539943:CFR protein, Staphylococcus aureus; D003030:Coagulase; D005839:Gentamicins; D012338:RNA, Ribosomal, 23S; D005672:Fusidic Acid; D064704:Levofloxacin; D000069349:Linezolid; D008712:Methicillin; D012293:Rifampin
keywords: Bloodstream; Daptomycin; Linezolid; Osteoarticular; Resistance; Staphylococci