Limited efficacy of adjuvant therapy with dexamethasone in preventing hearing loss due to experimental pneumococcal meningitis in the infant rat.
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.
Coimbra
Roney S
RS
Institute for Infectious Diseases, University of Bern, CH-3010 Bern, Switzerland.
Loquet
Gérard
G
Leib
Stephen L
SL
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
D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D003907:Dexamethasone