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

Muhamed-Kheir Taha (1) , Sara Thulin Hedberg (2) , Marek Szatanik (1) , Eva Hong (1) , Corinne Ruckly (1) , Raquel Abad (3) , Sophie Bertrand (4) , Françoise Carion (4) , Heike Claus (5) , Alejandra Corso (6) , Rocío Enríquez (3) , Sigrid Heuberger (7) , Waleria Hryniewicz (8) , Keith A. Jolley (9) , Paula Kriz (10) , Marta Mollerach (11) , Martin Musilek (10) , Arianna Neri (12) , Per Olcén (2) , Marina Pana (13) , Anna Skoczynska (8) , Cecilia Sorhouet Pereira (6, 11) , Paola Stefanelli (12) , Georgina Tzanakaki (14) , Magnus Unemo (2) , Julio A Vazquez (3) , Ulrich Vogel (5) , Izabela Wasko (8)

1 CNR - Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae
2 Örebro University Hospital [Örebro, Sweden]
3 ISC - Instituto de Salud Carlos III [Madrid]
4 WIV-ISP - Institut Scientifique de Santé Publique [Belgique] - Scientific Institute of Public Health [Belgium]
5 Institut für Hygiene und Mikrobiologie [Würzburg]
6 INEI - Instituto Nacional de Enfermedades Infecciosas- ANLIS Carlos Malbrán [Buenos Aires]
7 Austrian Agency for Health and Food Safety (AGES)
8 NRCBM - National Reference Centre for Bacterial Meningitis [Warsaw, Poland]
9 Department of Zoology [Oxford]
10 National Institute of Public Health [Prague]
11 UBA - Universidad de Buenos Aires [Buenos Aires]
12 Department of Infectious, Parasitic and Immune-Mediated Diseases [Rome]
13 Cantacuzino Institute [Romania]
14 National Meningitis Reference Laboratory

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.

Domains: Bacteriology

Muhamed-Kheir Taha, Sara Thulin Hedberg, Marek Szatanik, Eva Hong, Corinne Ruckly, et al.. Multicenter Study for Defining the Breakpoint for Rifampin Resistance in Neisseria meningitidis by rpoB Sequencing.. Antimicrobial Agents and Chemotherapy, 2010, 54 (9), pp.3651-3658. ⟨10.1128/AAC.00315-10⟩. ⟨pasteur-02085459⟩