Genome Analysis of Dual-Resistant Invasive Meningococcal Disease Isolates

Recent cases of dual-resistant invasive meningococcal disease (IMD) in the United States indicate that there is a need for effective antimicrobial resistance surveillance programs. These findings from a meningococcal genome analysis were published in Clinical Infectious Diseases.

Meningococcal isolates (N=2097) from infected patients in the United States from 2011 to 2020 underwent whole genome sequencing. Genes associated with antimicrobial resistance were identified by using the Basic Local Alignment Search Tool (BLAST). Isolates were assessed for β-lactamase activity with a nitrocefin test and for susceptibility to ampicillin, azithromycin, cefotaxime, ceftriaxone, chloramphenicol, ciprofloxacin, levofloxacin, meropenem, minocycline, penicillin, rifampin, and trimethoprim-sulfamethoxazole in a broth microdilution test.

Isolates were Neisseria meningitidis subgroups B (n=773), C (n=580), Y (n=374), W (n=207), E (n=9), and Z (n=1); 153 could not be grouped. A total of 45 isolates were identified as having penicillin (bla_ROB-1) or ciprofloxacin (gyrA mutation) resistance, and 11 isolates were dual-resistant. Resistant isolates were collected every year except 2012, and all dual-resistant strains were collected from 2019 to 2020. All dual-resistant strains belonged to subgroup Y.

In a functional analysis of the isolates that carried a bla_ROB-1 penicillin resistance, all were resistant to penicillin, ampicillin, and trimethoprim-sulfamethoxazole, and 11 were resistant to ciprofloxacin and levofloxacin.

The IMD cases with bla_ROB-1 penicillin-resistant isolates were collected in 11 states. The greatest number of cases occurred in individuals 45 years and older (45%) or those younger than 1 year (18%), and 67% of patients with bla_ROB-1 penicillin-resistant isolates were Hispanic. Among those with available data, 29% had lived in or recently traveled to Mexico. The IMD cases with ciprofloxacin-resistant isolates were reported in 8 states. The greatest number of cases occurred in individuals aged 45 years of age and older (33%) or those aged 22 to 44 years (33%).

Compared with N meningitidis genomes collected outside the United States, isolates with bla_ROB-1 and wild-type gyrA-quinolone resistance determining region (QRDR) allele 2 originated from 6 countries, and isolates with bla_TEM-1 originated from 5 countries. All bla_ROB-1 genes were identical to the Haemophilus influenzae reference sequence.

Isolates with gyrA T91I or T91F mutations clustered with N lactamica, N gonorrhoeae, N cinerea, and N subflava and T91I gyrA-QRDR with N lactamica.

This study was likely limited by the amount of available data with which to compare the genomes of the meningococcal isolates. However, these data emphasized the importance of antimicrobial resistance surveillance, especially because of the recent rise in the emergence of dual-resistant N meningitidis strains. Resistance status should be confirmed in patients prior to the administration of antibiotics.

Reference

Potts CC, Retchless AC, McNamara LA, et al; the Antimicrobial-resistant Neisseria meningitis team. Acquisition of ciprofloxacin resistance among an expanding clade of β–lactamase positive, serogroup Y Neisseria meningitidis in the United States. Clin Infect Dis. Published online April 26, 2021. doi:10.1093/cid/ciab358