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Red Book Online Outbreaks: Penicillin-resistant and Ciprofloxacin-resistant Neisseria Meningitis

December 21, 2022

Penicillin- and ciprofloxacin-resistant, β-lactamase-producing N. meningitidis has emerged in the U.S. During 2019–2020, 11 cases of invasive meningococcal disease caused by penicillin-resistant and ciprofloxacin-resistant Neisseria meningitidis serogroup Y (NmY meningococcal disease) isolates were detected in California, Georgia, Kansas, Maryland, New Jersey, New York, North Carolina, Pennsylvania, and Texas. Cases caused by dual-resistant strains continue to be reported in the U.S. in 2021.

From 2013 to 2020 in the U.S., there were an additional 22 cases of invasive meningococcal disease caused by N. meningitidis serogroup Y (NmY) isolates containing a blaROB-1 β-lactamase gene conferring penicillin resistance, but which did not have mutations associated with ciprofloxacin-resistance. These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the US since 2013. For more information, visit: Meningococcal Disease Surveillance | CDC

Clinical Guidance

  • Presentation: Bacterial meningitis symptoms include sudden onset of fever, headache, and stiff neck, often is accompanied by nausea, vomiting, photophobia, and altered mental status. Meningococcal bloodstream infection (septicemia or meningococcemia) may present with fever, chills, malaise, limb pain, prostration, and a rash that initially can be macular or maculopapular but typically becomes petechial or purpuric within hours. Newborns and infants may not have the classic symptoms but instead may be slow, inactive, or irritable; or have poor feeding, bulging fontanelle, and abnormal reflexes. Typically, symptoms develop within 3 to 7 days after exposure.
  • Diagnosis: Cultures of blood and cerebrospinal fluid (CSF) should be collected from patients with suspected invasive meningococcal disease.
  • Populations at highest risk: All pediatric populations at risk, particularly children under 1 year. Cases caused by β -lactamase-positive NmY were reported from 12 geographically disparate states; the majority of cases (22 of 33, 67%) occurred in Hispanic persons.
  • Complications: Sequelae associated with meningococcal disease occur in up to 20% of survivors and include hearing loss, neurologic disability, digit or limb amputations, and skin scarring. In addition, patients may experience subtle long-term neurologic deficits, such as impaired school performance, behavioral problems, and attention deficit disorder.
  • Precautions: Regardless of immunization status, close contacts including household contacts of all people with invasive meningococcal disease (see Red Book Table 3.35), whether endemic or in an outbreak situation, are at high risk of infection and should promptly receive chemoprophylaxis. Chemoprophylaxis should be provided even if the close contact has received meningococcal vaccine. The decision to give chemoprophylaxis to other contacts is based on risk of contracting invasive disease related to specific exposure to the secretions from the infected patient. Throat and nasopharyngeal cultures are not recommended, because these cultures are of no value in deciding who should receive chemoprophylaxis.
  • Risk mitigation: Promote vaccination of recommended meningococcal vaccines to eligible patients. In the United States, 3 meningococcal vaccines are licensed and available for use in children and adults against serogroups A, C, W, and Y (MenACWY), and 2 vaccines are licensed for people 10 through 25 years of age against serogroup B (MenB). All 3 MenACWY vaccines are protein conjugate vaccines, while the 2 MenB vaccines are protein-based vaccines using 2 different technologies. The Red Book Table 3.37 (p 526) and Table 3.38 (p 528) provide recommendations on meningococcal vaccines.
  • Treatment and Prophylaxis:
    • Ceftriaxone or cefotaxime are recommended first-line agents for empiric treatment of meningococcal disease.
    • Detection of geographically diverse cases caused by penicillin-resistant and ciprofloxacin-resistant Neisseria meningitidis serogroup Y (NmY meningococcal disease) in the US has implications for treatment and prophylaxis of meningococcal disease.
      • Healthcare providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin for treatment.
      • In states that have experienced meningococcal disease cases caused by ciprofloxacin-resistant strains during the past 1-2 years, clinicians and public health staff should consider antimicrobial susceptibility testing (AST) on meningococcal isolates to inform prophylaxis decisions.
      • Antimicrobial susceptibility testing should not delay the initiation of prophylaxis.
      • Recommended prophylaxis for close contacts of persons with meningococcal disease includes either a 2-day course of rifampin, a single injection of ceftriaxone or a single dose of ciprofloxacin (see Red Book Table 3.36). Ciprofloxacin should not be used if fluoroquinolone-resistant strains of Nm have been identified in the community.
      • Azithromycin may be considered for prophylaxis in the setting of concern for ciprofloxacin resistance, and challenges exist with rifampin and ceftriaxone use. However, data are limited and minimum inhibitory concentrations at the limit of susceptibility have been detected in some meningococcal isolates tested from a carriage study.
  • Reporting and assistance:
    • State and territorial health departments should continue to submit all meningococcal isolates to the CDC for AST and whole genome sequencing (WGS).
    • States that conduct their own AST, β-lactamase screening, or WGS should share results and sequences with the CDC.
    • Although the COVID-19 pandemic may create challenges for submitting meningococcal isolates and collecting epidemiologic data, this information is important for understanding the complete geographic and temporal distribution of these penicillin- and ciprofloxacin-resistant meningococci.
    • For cases with isolates determined to be β-lactamase screen-positive or ciprofloxacin-resistant, jurisdictions are requested to complete a supplemental case report form (available on request from meningnet@cdc.gov); forms can be submitted to CDC via secure email (meningnet@cdc.gov) or FTP site.


Pediatric Practice Tools and Info

CDC: Meningococcal Vaccination | For Providers


Public Health Resources

CDC: Meningitis

CDC: Meningococcal Vaccination


Information for Patients and Caregivers

AAP HealthyChildren.org: Meningitis in Infants and Children
In Spanish: Meningitis en niños y bebés


Infection Prevention and Control Resources

AAP: Project Firstline

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