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Childhood Bacterial Meningitis Brings Hefty Late Sequelae


 

EXPERT ANALYSIS FROM A CONFERENCE ON PEDIATRIC INFECTIOUS DISEASES

VAIL, COLO. – Half of all childhood bacterial meningitis survivors have sequelae 5 years or more afterward, according to a systematic literature review.

Intellectual and/or behavioral deficits accounted for 78% of the long-term sequelae. These are lingering aftereffects that impose academic and behavioral limitations, not the very common minor neurologic deficits that often resolve soon after discharge, Dr. Ann-Christine Nyquist noted at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.

Dr. Ann-Christine Nyquist

She said she presented highlights of a literature analysis conducted by Dr. Aruna Chandran and coworkers at Johns Hopkins University, Baltimore, because she considers this to be the first good-quality, comprehensive data on the long-term sequelae of childhood bacterial meningitis.

Most prior studies have focused on sequelae present in the first months following a childhood episode of bacterial meningitis; the Johns Hopkins analysis was restricted to studies featuring a minimum follow-up of 5 years. It provides a far more complete picture of the disease’s underappreciated impact, noted Dr. Nyquist, a pediatric infectious diseases specialist at the University of Colorado at Denver.

The analysis included 1,433 children who survived an episode of bacterial meningitis, 49% of whom had one or more long-term sequelae. Seventy-eight percent of the 1,012 recorded long-term sequelae were behavioral and/or intellectual deficits. Specifically, 45% of all long-term sequelae were categorized as low intelligence quotient/cognitive impairment, 7.6% as behavioral deficits, and 2.4% as attention-deficit/hyperactivity disorder.

Gross neurologic deficits accounted for 14.3% of long-term sequelae. Another 6.7% consisted of hearing deficits (Pediatr. Infect. Dis. J. 2011;30:3-6).

These data underscore the importance of prompt diagnosis and effective treatment of pediatric bacterial meningitis, Dr. Nyquist emphasized.

She pointed out that the most recent Cochrane review of corticosteroids for acute bacterial meningitis came down squarely on the pro side because of the significant benefit in terms of reduced sequelae. The analysis included 24 randomized, placebo-controlled clinical trials in 4,041 subjects, both children and adults.

The Cochrane group found that in high-income countries, the use of adjunctive dexamethasone reduced the risk of severe hearing loss by 49%, of any hearing loss by 42%, and of short-term neurologic sequelae by 36%. Adjunctive steroids weren’t associated with significant decreases in overall mortality or long-term neurologic sequelae; however, in the subgroup with Streptococcus pneumoniae meningitis, the trend for reduced mortality did achieve statistical significance (Cochrane Database Syst. Rev. 2010 Sept. 8;CD004405).

"I think within our infectious disease practice group, most of us would probably go on the side of giving dexamethasone in all cases of suspected bacterial meningitis in infants and children if we have the opportunity to make that recommendation," Dr. Nyquist said.

The dose is 0.4 mg/kg of dexamethasone given every 12 hours for a total of four doses over a period of 2 days, administered starting before or at initiation of parenteral antibiotic therapy.

A couple of caveats: Only limited data exist on the use of adjunctive corticosteroids in neonates with acute bacterial meningitis. And steroid therapy in any age group poses a challenge because its anti-inflammatory action reduces the permeability of the damaged CNS capillary membrane – the blood-brain barrier – at just the time when the physician is trying to get antibiotics into the CNS.

The inhibitory effect of steroids is greatest on large-molecular-weight or hydrophobic antibiotics. Vancomycin is the antibiotic affected most; levels are reduced by 42%-77%. Ampicillin levels are decreased by 57%, gentamicin levels are reduced by 30%, and ceftriaxone levels have been shown in various studies to be either unaffected or decreased by 45%, according to Dr. Nyquist.

She said that that she serves as a consultant to and has received speaking honoraria from Merck, Sanofi Pasteur, and Novartis.

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