title: Multicenter study for defining the breakpoint for rifampin resistance in Neisseria meningitidis by rpoB sequencing.
abstract: Identification of clinical isolates of Neisseria meningitidis that are resistant to rifampin is important to avoid prophylaxis failure in contacts of patients, but it is hindered by the absence of a breakpoint for resistance, despite many efforts toward standardization. We examined a large number (n = 392) of clinical meningococcal isolates, spanning 25 years (1984 to 2009), that were collected in 11 European countries, Argentina, and the Central African Republic. The collection comprises all clinical isolates with MICs of > or = 0.25 mg/liter (n = 161) received by the national reference laboratories for meningococci in the participating countries. Representative isolates displaying rifampin MICs of < 0.25 mg/liter were also examined (n = 231). Typing of isolates was performed, and a 660-bp DNA fragment of the rpoB gene was sequenced. Sequences differing by at least one nucleotide were defined as unique rpoB alleles. The geometric mean of the MICs was calculated for isolates displaying the same allele. The clinical isolates displaying rifampin MICs of > 1 mg/liter possessed rpoB alleles with nonsynonymous mutations at four critical amino acid residues, D542, H552, S548, and S557, that were absent in the alleles found in all isolates with MICs of < or = 1 mg/liter. Rifampin-susceptible isolates could be defined as those with MICs of < or = 1 mg/liter. The rpoB allele sequence and isolate data have been incorporated into the PubMLST Neisseria database (http://pubmlst.org/neisseria/). The rifampin-resistant isolates belonged to diverse genetic lineages and were associated with lower levels of bacteremia and inflammatory cytokines in mice. This biological cost may explain the lack of clonal expansion of these isolates.
authors.affiliation: Institut Pasteur, National Reference Centre for Meningococci, 28 Rue du Dr. Roux, Paris, France. mktaha@pasteur.fr
authors.forename: Muhamed-Kheir
authors.initials: MK
authors.lastname: Taha
authors.forename: Sara Thulin
authors.initials: ST
authors.lastname: Hedberg
authors.forename: Marek
authors.initials: M
authors.lastname: Szatanik
authors.forename: Eva
authors.initials: E
authors.lastname: Hong
authors.forename: Corinne
authors.initials: C
authors.lastname: Ruckly
authors.forename: Raquel
authors.initials: R
authors.lastname: Abad
authors.forename: Sophie
authors.initials: S
authors.lastname: Bertrand
authors.forename: Francoise
authors.initials: F
authors.lastname: Carion
authors.forename: Heike
authors.initials: H
authors.lastname: Claus
authors.forename: Alejandra
authors.initials: A
authors.lastname: Corso
authors.forename: Rocío
authors.initials: R
authors.lastname: Enríquez
authors.forename: Sigrid
authors.initials: S
authors.lastname: Heuberger
authors.forename: Waleria
authors.initials: W
authors.lastname: Hryniewicz
authors.forename: Keith A
authors.initials: KA
authors.lastname: Jolley
authors.forename: Paula
authors.initials: P
authors.lastname: Kriz
authors.forename: Marta
authors.initials: M
authors.lastname: Mollerach
authors.forename: Martin
authors.initials: M
authors.lastname: Musilek
authors.forename: Arianna
authors.initials: A
authors.lastname: Neri
authors.forename: Per
authors.initials: P
authors.lastname: Olcén
authors.forename: Marina
authors.initials: M
authors.lastname: Pana
authors.forename: Anna
authors.initials: A
authors.lastname: Skoczynska
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sorhouet Pereira
authors.forename: Paola
authors.initials: P
authors.lastname: Stefanelli
authors.forename: Georgina
authors.initials: G
authors.lastname: Tzanakaki
authors.forename: Magnus
authors.initials: M
authors.lastname: Unemo
authors.forename: Julio A
authors.initials: JA
authors.lastname: Vázquez
authors.forename: Ulrich
authors.initials: U
authors.lastname: Vogel
authors.forename: Izabela
authors.initials: I
authors.lastname: Wasko
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000187:drug effects / Q000235:genetics*; D010802:Phylogeny; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012293:Rifampin