Intermediate Resistance to Penicillin, Ampicillin Common in Neisseria meningitidis Isolates

Researchers conducted an antimicrobial resistance survey that assessed Neisseria meningitidis isolates collected from patients in the United States between 2012 and 2016.

Results from a study that assessed isolates of Neisseria meningitidis collected from patients with invasive meningococcal disease (IMD) found that more than 25% of isolates had intermediate susceptibility to penicillin and ampicillin. These findings were published in The Journal of Infectious Diseases.

Researchers conducted an antimicrobial resistance (AMR) survey using data captured by the Centers for Disease Control and Prevention (CDC) that assessed N meningitidis isolates collected from patients with IMD between 2012 and 2016. All N meningitidis isolates were detected via culture and polymerase chain reaction testing. A total of 508 isolates were included in the survey. Broth microdilution was used to determine whether isolates were susceptible to clinically relevant antibiotics, and whole-genome sequencing was used to characterize resistance mechanisms. In addition, strains of Streptococcus pneumonia and Escherichia coli were used as quality control.

Among the N meningitidis isolates assessed, all were found to be susceptible to cefotaxime, ceftriaxone, meropenem, rifampin, minocycline, and azithromycin. Decreased antimicrobial susceptibility was observed for 5 antibiotics, including ampicillin, penicillin G, ciprofloxacin, levofloxacin, and trimethoprim-sulfamethoxazole. Further analysis of these antibiotics showed that 483 isolates were resistant to trimethoprim-sulfamethoxazole, and fewer than 6 were resistant to ampicillin, penicillin, ciprofloxacin, and levofloxacin. In addition, intermediate susceptibility to penicillin G and ampicillin was found among 208 and 229 N meningitidis isolates, respectively.

After stratification by year of collection, no significant variation was found among the isolates that were resistant to penicillin G (P >.70), with similar variation found among isolates that were resistant to ampicillin. Of the 208 isolates that conferred resistance to penicillin G, 164 (78.8%) were associated with mutations commonly found in penA alleles, including F504L, A510V, 1515V, H541N, and I566V. On analysis of 4 N meningitidis isolates with intermediate resistance to ciprofloxacin and 2 with resistance to levofloxacin, only 1 conferred intermediate resistance to both antibiotics and showed decreased susceptibility to fluoroquinolones.

This study was limited by the inability to determine whether findings that showed some isolates conferred resistance to penicillin were clinically significant. In addition, none of the patients involved in this survey exclusively received treatment with penicillin.

According to the researchers, “…[these findings] highlight the continued importance of N meningitidis AMR surveillance in the United States to monitor trends, paired with genotypic investigations to understand the underlying mechanisms of resistance.”


Potts CC, Rodriguez-Rivera LD, Retchless AC, et al. Antimicrobial susceptibility survey of invasive neisseria meningitidis, United States 2012-2016. J Infect Diseas. Published online March 10, 2022. doi:10.1093/infdis/jiac046