title: Limited efficacy of adjuvant therapy with dexamethasone in preventing hearing loss due to experimental pneumococcal meningitis in the infant rat.
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.
authors.affiliation: Institute for Infectious Diseases, University of Bern, CH-3010 Bern, Switzerland.
authors.forename: Roney S
authors.initials: RS
authors.lastname: Coimbra
authors.forename: Gérard
authors.initials: G
authors.lastname: Loquet
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002648:Child; D003051:Cochlea / Q000033:anatomy & histology / Q000473:pathology; D003907:Dexamethasone / Q000627:therapeutic use*; D016057:Evoked Potentials, Auditory, Brain Stem; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008586:Meningitis, Pneumococcal / Q000150:complications / Q000188:drug therapy; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D003907:Dexamethasone