Progression of antibiotic resistance in Neisseria meningitidis

SUMMARYThe human pathogen Neisseria meningitidis (Nm) is the causative agent of invasive meningococcal disease (IMD), usually presenting as meningitis, bacteremia, or sepsis. Unlike Neisseria gonorrhoeae, antibiotic resistance in Nm has developed slowly. However, in the last two decades and with the reemergence of IMD following the COVID-19 pandemic, antibiotic-resistant Nm isolates, especially to penicillin and fluoroquinolones, have progressively increased. Recent worldwide studies of penicillin intermediate and resistant Nm isolates and the PubMLST global database reveal a notable increase in fully penicillin-resistant isolates since 2016, mediated by mosaic penA alleles or the β-lactamase genes bla_ROB-1 and bla_TEM-1. Fluoroquinolone-resistant isolates, mediated by gyrA mutations, have increased since 2005. Also, while still exceptionally rare, four Nm isolates have been identified with third-generation cephalosporin-resistance since 2011. We review the emergence of antibiotic resistance determinants and lineages in Nm, the resistance to agents previously or currently used in treatment or chemoprophylaxis, and summarize updated treatment and prevention guidelines for IMD. Special populations (e.g., individuals on complement inhibitors) and antibiotic resistance in Nm urethritis isolates are also reviewed. The increasing number of resistant Nm isolates worldwide affects chemoprophylaxis and treatment options for IMD and emphasizes the need for enhanced global surveillance of antibiotic resistance in Nm.