Meningococcal Mutations: Tip of the Iceberg?

Fluoroquinolones, rifampin, and ceftriaxone have been widely used as chemoprophylaxis for close contacts of patients with meningococcal infection. Now, fluoroquinolone-resistant Neisseria meningitidis has emerged in North America.

From January 2007 through January 2008, three cases of infection with ciprofloxacin-resistant N. meningitidis were identified in the U.S. The patients were from the upper Midwest (Minnesota and North Dakota), but no epidemiologic links were identified among them, and none had recently traveled outside the U.S. Screening of 155 invasive N. meningitidis isolates received through the Active Bacterial Core surveillance system during the same period yielded an additional ciprofloxacin-resistant isolate, from California.

Molecular characterization of the three upper midwestern isolates indicated that they belonged to the same clonal complex. All harbored a mutation in the gyrA gene that is associated with fluoroquinolone resistance. The gyrA gene from the California isolate also showed the same mutation, although gene sequencing suggested that the mutation was acquired differently in this strain (point mutation) than in the upper midwestern strains (horizontal transfer from the commensal Neisseria lactamica).

This occurrence recalls events associated with the initial recognition of increasing penicillin resistance among pneumococcal isolates in the late 1980s. At that time, in vitro susceptibility testing was not routinely performed on all isolates. In my opinion, the detection of ciprofloxacin-resistant N. meningitidis in the U.S. and abroad mandates that susceptibility testing be performed in all cases of meningococcal disease.

— Larry M. Baddour, MD

The JW Pediatrics and Adolescent Medicine Perspective

When faced with a case of invasive meningococcal disease, practitioners must decide the best prophylactic regimen for close contacts. I agree with the current regional health advisory issued for eastern North Dakota and western Minnesota, recommending that ciprofloxacin not be used. However, in other areas of the country, the long-standing recommendation to use rifampin, ceftriaxone, or ciprofloxacin still applies. Whichever regimen is chosen, contacts should be told to take the medication as soon as possible and to notify a physician if any symptoms develop. All the isolates described were N. meningitidis type B, which is not contained in the new meningococcal conjugate vaccine. At the time of an exposure, however, the serotype is not known, and the situation provides an excellent opportunity to vaccinate individuals for whom immunization is indicated and approved.

— Peggy Sue Weintrub, MD