e Meningococcal gyrA gene sequence data, MICs, and mouse infection were used to define the ciprofloxacin breakpoint for Neisseria meningitidis. Residue T91 or D95 of GyrA was altered in all meningococcal isolates with MICs of >0.064 g/ml but not among isolates with MICs of <0.032 g/ml. Experimental infection of ciprofloxacin-treated mice showed slower bacterial clearance when GyrA was altered. These data suggest a MIC of >0.064 g/ml as the ciprofloxacin breakpoint for meningococci and argue for the molecular detection of ciprofloxacin resistance. N eisseria meningitidis is a Gram-negative encapsulated bacterium isolated only from humans, where it may provoke severe invasive infections (mainly septicemia and meningitis). Management of meningococcal disease requires prompt treatment of patients, as well as vaccination and/or chemoprophylaxis of contacts. The antibiotics currently recommended for chemoprophylaxis are rifampin, ciprofloxacin, and ceftriaxone (1). The emergence and expansion of meningococcal clones resistant to these antibiotics may jeopardize these recommendations. Ciprofloxacin resistance in meningococci was earlier linked to mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene (encodes subunit A of DNA gyrase) but no mutations in the QRDR of gyrB, parC, and parE (2). Here we correlate gyrA mutations and their in vivo impact on ciprofloxacin MICs for meningococcal clinical isolates.This study examined all of the available meningococcal isolates collected from 1995 to 2011 with ciprofloxacin MICs of Ն0.064 g/ml (n ϭ 19) in four countries (France, Italy, Spain, and Sweden). Representative isolates with ciprofloxacin MICs of Յ0.032 g/ml (n ϭ 177) were also tested, as were two isolates of N. gonorrhoeae and N. cinerea with ciprofloxacin MICs of 0.250 and 0.125 g/ml, respectively. Isolate typing was performed as previously described (3), and all those data are available at the Neisseria

Invasive disease caused by Neisseria meningitidis serogroup W (MenW) has historically had a low incidence in Sweden, with an average incidence of 0.03 case/100,000 population from 1995 to 2014. In recent years, a significant increase in the incidence of MenW has been noted in Sweden, to an average incidence of 0.15 case/100,000 population in 2015 to 2016. In 2017 (1 January to 30 June), 33% of invasive meningococcal disease cases (7/21 cases) were caused by MenW. In the present study, all invasive MenW isolates from Sweden collected in 1995 to June 2017 (n = 86) were subjected to whole-genome sequencing to determine the population structure and to compare isolates from Sweden with historical and international cases. The increase of MenW in Sweden was determined to be due to isolates belonging to the South American sublineage of MenW clonal complex 11, namely, the novel U.K. 2013 lineage. This lineage was introduced in Sweden in 2013 and has since been the dominant lineage of MenW.

No abstract

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y has increased in Europe, especially in Scandinavia. In Sweden, serogroup Y is now the dominating serogroup, and in 2012, the serogroup Y disease incidence was 0.46/100,000 population. We previously showed that a strain type belonging to sequence type 23 was responsible for the increased prevalence of this serogroup in Sweden. The objective of this study was to investigate the serogroup Y emergence by whole-genome sequencing and compare the meningococcal population structure of Swedish invasive serogroup Y strains to those of other countries with different IMD incidence. Whole-genome sequencing was performed on invasive serogroup Y isolates from 1995 to 2012 in Sweden (n = 186). These isolates were compared to a collection of serogroup Y isolates from England, Wales, and Northern Ireland from 2010 to 2012 (n = 143), which had relatively low serogroup Y incidence, and two isolates obtained in 1999 in the United States, where serogroup Y remains one of the major causes of IMD. The meningococcal population structures were similar in the investigated regions; however, different strain types were prevalent in each geographic region. A number of genes known or hypothesized to have an impact on meningococcal virulence were shown to be associated with different strain types and subtypes. The reasons for the IMD increase are multifactorial and are influenced by increased virulence, host adaptive immunity, and transmission. Future genome-wide association studies are needed to reveal additional genes associated with serogroup Y meningococcal disease, and this work would benefit from a complete serogroup Y meningococcal reference genome.

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.