Multicenter Study for Defining the Breakpoint for Rifampin Resistance in Neisseria meningitidis by rpoB Sequencing

作者:Taha Muhamed Kheir*; Hedberg Sara Thulin; Szatanik Marek; Hong Eva; Ruckly Corinne; Abad Raquel; Bertrand Sophie; Carion Francoise; Claus Heike; Corso Alejandra; Enriquez Rocio; Heuberger Sigrid; Hryniewicz Waleria; Jolley Keith A; Kriz Paula; Mollerach Marta; Musilek Martin; Neri Arianna; Olcen Per; Pana Marina; Skoczynska Anna; Sorhouet Pereira Cecilia; Stefanelli Paola; Tzanakaki Georgina; Unemo Magnus; Vazquez Julio A; Vogel Ulrich; Wasko Izabela
来源:Antimicrobial Agents and Chemotherapy, 2010, 54(9): 3651-3658.
DOI:10.1128/AAC.00315-10

摘要

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 >= 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 <= 1 mg/liter. Rifampin-susceptible isolates could be defined as those with MICs of <= 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.

  • 出版日期2010-9