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Bacterial Meningitis: Gains Made with Antibiotics, but Demographics of DisorderHave Changed

Moran, Mark

doi: 10.1097/01.NT.0000399928.42836.c2
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New data on rates of bacterial meningitis point to how preventive advances — in this case, the pneumococcal and Hib conjugate vaccines for children — can alter the demographic profile of disease. And they underscore the still deadly nature of the condition with case mortality rates remaining almost unchanged.

Rates of bacterial meningitis have decreased but mortality has declined only marginally while the burden of disease has shifted to the elderly. These were the major findings of an analysis of data on cases of bacterial meningitis during 1998–2007 in the May 26 New England Journal of Medicine.

These findings will not change existing clinical recommendations for antibiotic treatment, but they do point to how preventive advances — in this case, the pneumococcal and Hib conjugate vaccines for children — can alter the demographic profile of disease. And they underscore the still deadly nature of the condition with case mortality rates remaining almost unchanged.

“We have done a very good job of reducing the likelihood of bacterial meningitis among our younger population,” said senior study author Michael Thigpen, MD, medical epidemiologist with the Centers for Disease Control and Prevention. “With the introduction of the heptavalent protein-polysaccharide pneumococcal conjugate vaccine (PCV7) in 2000, and the H. influenzae type b [Hib] vaccine in 1990, we have managed to reduce rates of bacterial meningitis in children.”

The significant decline in incidence among children occurred in those over age one, but among neonates incidence remained high. In fact, incidence declined significantly over the surveillance period within all age groups (though non-significantly for adults) except for patients under two months of age. And throughout the surveillance period, incidence also remained high for black patients of any age.

“We have not done as well in terms of affecting the incidence of bacterial meningitis among older people,” Dr. Thigpen told Neurology Today. “This explains why there is less occurrence of bacterial meningitis overall, but not much change among adults.”

He added: “The other take-home message for clinicians is that despite advances in prevention for some populations, the case fatality rate has not changed among the people who do get bacterial meningitis, and it remains deadly.”

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Dr. Thigpen and colleagues analyzed data on cases of bacterial meningitis reported among residents in eight surveillance areas of the Emerging Infections Programs Network, consisting of approximately 17.4 million persons, between 1998 and 2007. The eight areas included San Francisco county in California; the state of Connecticut; the 20-county area of Atlanta; a six-county area of Baltimore; the seven-county area of Minneapolis-St. Paul; a seven-county area of Rochester, NY; a three-county area of Portland, Maine; and five urban counties of Tennessee.

The investigators defined -bacterial meningitis as the presence of H. influenzae, streptococcus pneumoniae, group B streptococus, Listeria monocytogenes, or Neisseria meningitidis in CSF or other normally sterile sites in association with a clinical diagnosis of meningitis.

They identified 3,188 patients with bacterial meningitis; of 3155 patients for whom outcome data were available, 466 (14.8 percent) died. Breaking mortality data down into two distinct surveillance periods — 1998–1999 and 2006–2007 — the investigators found a non-significant decline from 15.7 percent in 1998–1999 to 14.3 in 2006–2007.

The incidence of meningitis declined by 31 percent during the surveillance period. And at the same time, the median age of patients increased from 30.3 years in 1998–1999 to 41.9 years in 2006–2007. (For more on the study data, see “Bacterial Meningitis Analysis: Causative Pathogens and Mortality Figures.”)

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Neurology Today Associate Editor Kenneth L. Tyler, MD, who reviewed the analysis for Neurology Today, said nothing in the report will cause significant changes in recommended empiric antibiotic coverage. “The traditional coverage typically utilized is a third generation cephalosporin such as -ceftriaxone or cefotaxime plus vancomycin,” said Dr. Tyler, Reuler-Lewin Family Professor and chair of the department of neurology at the University of Colorado-Denver School of Medicine. “The vancomycin covers PCN/cephalosporin resistant pneumococci which are now increasingly prevalent. In patients over the age of 50 and those below the age of one month, ampicillin is added to provide better coverage against listeria.”

He noted that in patients who have penetrating head trauma related to a skull fracture or recent neurosurgery, clinicians may prescribe cefepime or ceftazidime as the cephalosporin of choice to provide enhanced coverage of pseudomonas and other aerobic gram-negative bacteria. Treatment of immunosuppressed patients includes similar agents but may need to be expanded based on the specific situation and type of immune-compromise, he said.

Regarding duration of treatment, Dr. Tyler said there have been few comparative studies. “We typically go about a week for meningococcus and H. flu, 10-14 days for pneumococcus, and 21 days for gram negatives and Listeria,” he said. “In some cases therapy is adjusted based on duration after first negative culture.”

Consensus regarding the benefits of adjunctive steroid therapy has recently undergone some changes, especially with adults for whom the evidence of efficacy has been somewhat weaker. “Some guidelines for example -suggested use in adults only if evidence suggesting pneumococcal meningitis,” he told Neurology Today. “But the most recent meta-analyses studies and reviews -suggest that although steroids do no harm, the previous conclusions in individual studies about potential benefits in terms of reduced mortality and reduced sequelae may have been overstated.



“Some experts now feel that based on this newer data that there is little real advantage to adjunctive steroids, regardless of age or organism. However, most guidelines pre-date these studies and still indicate they are a potential option. So I think until these guidelines are revised either approach is defensible and within the standard of care.”

Dr. Thigpen said that clinically the most important finding from the surveillance may be the relatively unchanging mortality data. “New treatments may be necessary to make advances in improving mortality among patients with bacterial meningitis, but the critical mainstay of clinical management remains early recognition and appropriate initiation of antibiotics.”

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Following are some of the relevant findings regarding causative pathogens and mortality figures in different age groups:

  • Among 587 cases of bacterial meningitis indentified among children from 2003-2007, group B streptococcus accounted for 86.1 percent of cases among those under two months of age, and N. meningitidis caused 45.9 percent of cases among those 11 to 17 years of age.
  • The case fatality rate was 6.9 percent among pediatric patients on average; nearly 10 percent had underlying immune-compromising or chronic medical conditions.
  • Among 1,083 identified cases of bacterial meningitis, S. pneumoniae was the most common pathogen.
  • The overall adult case fatality rate was 16.4 percent and the rate increased linearly with increasing age (8.9 percent among patients 18 to 34 years of age vs. 22.7 percent among those 65 years or older).
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Thigpen MC, Whitney CG, Schuchat A, et al, for the Emerging Infectious Program Network. Bacterial meningitis in the United States, 1998–2007. N Engl J Med 211; 364:2016-2025.
    ©2011 American Academy of Neurology