CDC Confirms Continued Susceptibility of N meningitidis to Indicated Antibiotics

Although Neisseria meningitidis remains a cause of life-threatening invasive meningococcal disease (IMD), its incidence has declined since 2005, and its resistance to indicated antibiotics remains rare, according to a new report from the Centers for Disease Control and Prevention (CDC).

The CDC examined meningococcal isolates from 2 domestic surveillance programs. The Active Bacterial Core Surveillance (ABC) is a population- and laboratory-based surveillance system for invasive bacterial pathogens in 10 catchment areas that comprised approximately 44.2 million US residents between 2012-2016. The national Enhanced Meningococcal Disease Surveillance (EMDS) provided isolates from 45 states and 3 large jurisdiction health departments, including the 10 in the ABC, for 2015-2016. Trends were also derived from comparison to the ABC isolates from 2004 to 2011.

"Phenotypic AMR (antimicrobial resistance) surveys of isolates collected from US IMD cases, along with genetic investigations into the mechanisms of resistance, are important for ensuring that current antibiotic treatment and prophylaxis recommendations remain relevant," explained lead author Caelin Potts, PhD, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC, Atlanta, GA, and colleagues.

The investigators note that although treatment resistant N meningitidis is uncommon in the US, there have been multiple reduced antimicrobial susceptibility phenotypes and resistance detected globally. These include reports, albeit infrequent and unconfirmed by the CDC, of resistance to third generation cephalosporins. In addition, reports of intermediate susceptibility to penicillins, consistent year-to-year in the US but increasing in several countries, have necessitated recommendations to confirm susceptibility to penicillin before its use.

"When comparing ABC isolates with reduced susceptibility by year, no clear changes in susceptibility were observed during 2012-2016," Potts and colleagues indicated.

The investigators report that all tested isolates were susceptible to the six antibiotics assessed: cefotaxime, ceftriaxone, meropenem, rifampin, minocycline and azithromycin. Isolates with reduced susceptibility to fluoroquinolones were rare, as were penicillin-resistant isolates.

There were, however, multiple patterns of reduced susceptibility to ampicillin, penicillin G, ciprofloxacin, levofloxacin; as well as to trimethoprim-sulfamethoxazole, which is not currently recommended to treat IMD. The investigators identified isolates containing allele 327 of the penA gene, which encodes penicillin binding protein 2. There have also been mosaic alleles in the penA gene that result in several amino acid substitutionslinked to intermediate susceptibility to penicillins.

"The increased penicillin-intermediate isolates could still pose a concern for individuals being treated with complement inhibitors, who sometimes receive long-term penicillin prophylaxis," Potts and colleagues cautioned.

In accompanying commentary, Muhamed-Kheir Taha, MD, PhD and Ala-Eddine Deghmane, PhD, Invasive Bacterial Infections Unit, Institut Pasteur, Paris, France, point out that beta-lactams are the usual recommended antibiotics to treat IMD; with other antibiotics commonly used for prophylaxis including rifampicin, ciprofloxacin and the third-generation cephalosporin, ceftriaxone.

They note that treatment is often initiated empirically before the results of antibiotic susceptibility testing are available, given the approximate 10% fatality of treated cases; and that approximately 25% of survivors suffer long-term sequelae.

"The surveillance in N meningitidis of resistance to antibiotics that are currently used for the treatment and prophylaxis of IMD is an important public health issue," Taha and Deghamane emphasize. "Standardized methods, protocols and breakpoints are key elements in this surveillance that require not only conventional methods but also molecular methods using nucleotide sequence-based typing."