Acquisition of Ciprofloxacin Resistance Among an Expanding Clade of beta-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 beta-lactamase gene (bla(ROB-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 bla(ROB-1)- or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing bla(ROB-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 bla(ROB-1) and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, bla(ROB-1)containing US isolates with wild-type gyrA were identified from 2013 to 2020. All 33 bla(ROB-1)-containing isolates formed a single clade, along with 12 bla(ROB-1)-containing isolates from 6 other countries. Two-thirds of bla(ROB-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 beta-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread.