Acquisition of Ciprofloxacin Resistance Among an Expanding Clade of ß-Lactamase-Positive, Serogroup Y Neisseria meningitidis in the United States.

BACKGROUND: Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 ß-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA) have been recently reported in the United States. METHODS: We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011 to February 2020 to identify IMD cases caused by strains with blaROB-1- or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. RESULTS: Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1- containing US isolates with wild-type gyrA were identified from 2013 to 2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from 6 other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to 6 CCs and contained 10 unique gyrA alleles; 7 were similar or identical to alleles from Neisseria lactamica or Neisseria gonorrhoeae. CONCLUSIONS: Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the United States. The emerging dual resistance is due to acquisition of ciprofloxacin resistance by ß-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread.

First description of a rifampicin-resistant Neisseria meningitidis serogroup Y strain causing recurrent invasive meningococcal disease in Hungary.

A Hungarian soldier previously immunized against Neisseria meningitidis by quadrivalent polysaccharide vaccine was twice infected with meningococci within six weeks. The patient was treated with ceftriaxone during both episodes and he successfully recovered. His close contacts received rifampicin prophylaxis. An investigation was performed to characterize the genetic background of the pathogens to ascertain if the recurrent invasive meningococcal disease was caused by the same strain and to find out the reason for reinfection. Both meningococci belonged to the fine type Y:P1.5-2,10-1:F4-1:ST-23. This is the first description of the Europe-wide prevalent N. meningitidis serogroup Y in Hungary. In the first episode, we found wild-type rpoB allele in the non-culturable sample implying the susceptibility to rifampicin. The culturable isolate from the second episode proved resistant to rifampicin and had a point mutation in the rpoB gene. The rifampicin resistance might have evolved during the prophylactic treatment of contacts. Previous immunization of the patient with polysaccharide vaccine was ineffective due to his immunodeficiency, thus immunization with conjugate vaccine was proposed. We have proposed the implementation of centralized rifampicin susceptibility testing of N. meningitidis strains within a defined time frame to intervene and administer appropriate prophylaxis to close contacts.

Meningococcal serotype Y myopericarditis.

Involvement of the pericardium in meningococcal disease is a well-recognized but rare complication. Isolated meningococcal pericarditis is defined as purulent pericarditis without clinical evidence of meningococcemia. Neisseria meningitidis serotypes C, B, and W135 have been previously described to cause pericarditis. This is the 1st case report of isolated meningococcal myopericarditis due to N. meningitidis serotype Y.

Annual report of the Australian Meningococcal Surveillance Programme, 2007.

In 2007 there were 242 laboratory-confirmed cases of invasive meningococcal disease analysed by the National Neisseria Network, a nationwide network of reference laboratories. The phenotypes (serogroup, serotype and serosubtype) and antibiotic susceptibility of 127 isolates of Neisseria meningitidis from invasive cases of meningococcal disease were determined and an additional 115 cases were confirmed by non-culture based methods. Nationally, 192 (85%) confirmed cases where a serogroup was determined were infected with serogroup B and 14 (6.2%) with serogroup C meningococci. The total number of confirmed cases was 29 fewer than the 271 cases identified in 2006. The only jurisdiction to record a substantial increase in laboratory confirmed cases was New South Wales and this was in sporadic cases of serogroup B infection. Typical primary and secondary disease peaks were observed in those aged 4 years or less and in adolescents and young adults respectively. Serogroup B cases predominated in all age groups and jurisdictions. The common phenotypes circulating in Australia were B:15:P1.7, B:4:P1.4 and C:2a:P1.5. No evidence of meningococcal capsular 'switching' was detected. About three-quarters of all isolates showed decreased susceptibility to the penicillin group of antibiotics (minimum inhibitory concentration [MIC] 0.06-0.5 mg/L). All isolates remained susceptible to rifampicin. A single serogroup B isolate had decreased susceptibility to ciprofloxacin (MIC 0.06 mg/L). This was the first local isolate of this type since the original report of this phenomenon in Australia in 2000.

Characterization of invasive serogroup Y meningococci in Italy: prevalence of ST-23 Complex/Cluster A3.

The percentage of Neisseria meningitidis serogroup Y isolated from patients with invasive meningococcal disease (IMD) in Italy has increased from 1998 to 2006. In this study, phenotypic features and genetic relatedness have been investigated in all serogroup Y meningococci isolated during that period. Multilocus sequence typing (MLST) identified the ST-23 complex/Cluster A3 as the major clonal complex in 88.8% of the strains. That complex included all strains belonging to the sequence type (ST) 23 isolated from 1998 to 2004, whereas the ST-3171 was prevalent among strains in the years 2005 and 2006. The STs 23 and 3171 differ for only one nucleotide in the phosphoglucomutase (pgm) housekeeping gene. Over 80% of serogroup Y ST-23 complex/Cluster A3 strains showed phenotype Y:14:NST and 85% of the latter resulted indistinguishable by pulsed-field gel electrophoresis analysis. In 2005, serogroup Y meningococci with decreased susceptibility to penicillin were isolated for the first time in Italy. In the following year, three of the seven strains showed this phenotype. The results of this study allow us to draw a profile of the molecular characteristics of invasive serogroup Y in Italy and will be helpful to monitor the spread of this serogroup in the next years.

Fatal acute cellulitis due to Neisseria meningitidis.

We describe the first fatal evolution of cellulitis due to Neisseria meningitidis serogroup Y involving an 85-year-old woman. She presented with an extensive cellulitis of the left side of the face, neck, and thorax and septic shock. In spite of active antibiotic therapy, evolution was rapidly fatal.