Drug-Resistant Meningococcal Bacteria Found in the United States, 2019–2020

Meningococcal disease, caused by the bacterium Neisseria meningitidis, strikes suddenly and kills 10%–15% of those who get it. Prompt empiric antibiotic treatment reduces illness and death, and antibiotic prophylaxis protects close contacts. In the United States these bacteria have usually been susceptible to the recommended drugs, including penicillin and ciprofloxacin. This report describes the detection of penicillin- and ciprofloxacin-resistant serogroup Y strains.

Summary

• Known before: most U.S. N. meningitidis isolates responded to the antibiotics recommended for treatment and prophylaxis.
• New here: during 2019–2020, isolates from 11 U.S. patients carried a blaROB-1 β-lactamase gene associated with penicillin resistance and mutations associated with ciprofloxacin resistance. Another 22 cases from 2013–2020 carried blaROB-1 without the ciprofloxacin mutations.
• What it means: ceftriaxone and cefotaxime can still be used to start treatment for bacterial meningitis, but susceptibility to penicillin should be confirmed before switching to penicillin or ampicillin. Prophylaxis failures and resistance should be monitored.

Background

Meningococcal disease is usually treated first with cefotaxime or ceftriaxone, which can be switched to penicillin or ampicillin once N. meningitidis is confirmed. Because close contacts are at higher risk, they are advised to take ciprofloxacin, rifampin or ceftriaxone as soon as a case is suspected.

Resistance to these drugs has been rare in the United States. Intermediate penicillin susceptibility is common, but its clinical meaning is unclear; true penicillin resistance is rare, and ciprofloxacin resistance uncommon — one cluster of three cases in 2007–2008 and occasional single cases. So susceptibility testing is not routinely done on meningococcal isolates.

How the strain was found

In January 2020, a N. meningitidis serogroup Y (NmY) isolate that produced a β-lactamase and resisted penicillin and ciprofloxacin was cultured from a patient in Maryland. When the Maryland Department of Health reported a second such case in February 2020, CDC set out to learn whether the pattern was more widespread.

• Health departments submit isolates to CDC about every 6 months. CDC asked them, through its secure Epi-X network, to send any 2019–2020 NmY isolates not yet submitted; 24 states and the District of Columbia responded with isolates or confirmation that none were available.
• CDC ran whole genome sequencing on all available isolates from U.S. invasive cases in 2011–2020 — 2,097 in all, 372 of them NmY — looking for blaROB-1 and ciprofloxacin-resistance mutations.
• Isolates with both underwent reference susceptibility testing, and states supplied case investigation data.

What turned up

• 11 serogroup Y isolates had blaROB-1 plus a T91I gyrA mutation linked to ciprofloxacin resistance.
• 22 more had blaROB-1 alone: 21 serogroup Y and 1 nongroupable.
• All 33 belonged to clonal complex 23: 30 (including all 11 ciprofloxacin-resistant ones) were sequence type 3587, 2 were 15379, and 1 was 13034.
• The 33 came from 12 states in 2013–2020.
• All 11 tested isolates produced β-lactamase and resisted penicillin and ciprofloxacin, but were susceptible to third-generation cephalosporins, rifampin and azithromycin.

The 33 isolates by quarter, 2013–2020: with blaROB-1 alone (dark) or with a ciprofloxacin-resistance mutation as well (light). Chart: CDC.

States reporting cases, 2013–2020, shaded by the number of penicillin- and ciprofloxacin-resistant isolates. Map: CDC.

Who was affected

Most cases were in young children and older adults. There were no known links among the 33, yet 22 (67%) were in Hispanic people, including 8 of the 11 with ciprofloxacin-resistant isolates. One patient died (case-fatality rate 3.0%).

The ethnicity of two Black patients was not reported; the rest were non-Hispanic.

What it means

This is a new, emerging strain, found in widely separated states, with consequences for both treatment and prophylaxis.

• Treatment: ceftriaxone and cefotaxime remain the first-line empiric drugs. Given the number of β-lactamase producers and the other good options, providers should check penicillin susceptibility before using penicillin or ampicillin.
• Prophylaxis: alternatives to ciprofloxacin are a 2-day course of rifampin or a single ceftriaxone injection, though both are harder to give. A single dose of azithromycin can be used where ciprofloxacin-resistant meningococci have been found, but only one published study shows it clears carriage.
• Beyond the United States: penicillin- and ciprofloxacin-resistant NmY isolates were found in El Salvador in 2017–2019; single blaROB-1 isolates still susceptible to ciprofloxacin have been reported in Canada and France. How widely the strain circulates is unknown.
• Gaps: not every case has an isolate to test — CDC received isolates for only 72% of cases in 2017 and 78% in 2018 — and the COVID-19 pandemic limited submissions, data collection and testing.

What health departments are asked to do

• Keep sending all meningococcal isolates to CDC for susceptibility testing and sequencing, and report suspected treatment or prophylaxis failures.
• Where ciprofloxacin-resistant cases have occurred in the past 1–2 years, consider susceptibility testing to guide prophylaxis — but never delay prophylaxis for it. Such testing requires rigorous protection from droplets and aerosols, including a biosafety cabinet, and microbiologists routinely exposed should be vaccinated.
• Share results and sequences from their own testing with CDC, and file a supplementary case report for β-lactamase-positive or ciprofloxacin-resistant cases.

Sources

Based on McNamara LA, Potts C, Blain AE, et al., "Detection of Ciprofloxacin-Resistant, β-Lactamase–Producing Neisseria meningitidis Serogroup Y Isolates — United States, 2019–2020," MMWR Morbidity and Mortality Weekly Report, volume 69, Centers for Disease Control and Prevention; a work of the United States government in the public domain.