Limited efficacy of adjuvant therapy with dexamethasone in preventing hearing loss due to experimental pneumococcal meningitis in the infant rat

Pediatr Res. 2007 Sep;62(3):291-4. doi: 10.1203/PDR.0b013e318123fb7c.

Abstract

Sensorineural hearing loss (SNHL) is the most common sequel of bacterial meningitis (BM) and is observed in up to 30% of survivors when the disease is caused by Streptococcus pneumoniae. BM is the single most important origin of acquired SNHL in childhood. Anti-inflammatory dexamethasone holds promises as potential adjuvant therapy to prevent SNHL associated with BM. However, in infant rats, pneumococcal meningitis (PM) increased auditory brainstem response (ABR) thresholds [mean difference = 54 decibels sound pressure level (dB SPL)], measured 3 wk after infection, irrespective to treatment with ceftriaxone plus dexamethasone or ceftriaxone plus saline (p < 0.005 compared with mock-infected controls). Moreover, dexamethasone did not attenuate short- and long-term histomorphologic correlates of SNHL. At 24 h after infection, blood-labyrinth barrier (BLB) permeability was significantly increased in infected animals of both treatment groups compared with controls. Three weeks after the infection, the averaged number of type I neurons per square millimeter of the Rosenthal's canal dropped from 0.3019 +/- 0.0252 in controls to 0.2227 +/- 0.0635 in infected animals receiving saline (p < 0.0005). Dexamethasone was not more effective than saline in preventing neuron loss (0.2462 +/- 0.0399; p > 0.05). These results suggest that more efficient adjuvant therapies are needed to prevent SNHL associated with pediatric PM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Anti-Inflammatory Agents / therapeutic use*
  • Child
  • Cochlea / anatomy & histology
  • Cochlea / pathology
  • Dexamethasone / therapeutic use*
  • Evoked Potentials, Auditory, Brain Stem
  • Hearing Loss, Sensorineural* / etiology
  • Hearing Loss, Sensorineural* / prevention & control
  • Humans
  • Meningitis, Pneumococcal* / complications
  • Meningitis, Pneumococcal* / drug therapy
  • Neurons / metabolism
  • Neuroprotective Agents / therapeutic use
  • Rats
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents
  • Neuroprotective Agents
  • Dexamethasone