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 ϭ 54 decibels sound pressure level (dB SPL)], measured 3 wk after infection, irrespective to treatment with ceftriaxone plus dexamethasone or ceftriaxone plus saline (p Ͻ 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 Ϯ 0.0252 in controls to 0.2227 Ϯ 0.0635 in infected animals receiving saline (p Ͻ 0.0005). Dexamethasone was not more effective than saline in preventing neuron loss (0.2462 Ϯ 0.0399; p Ͼ 0.05). These results suggest that more efficient adjuvant therapies are needed to prevent SNHL associated with pediatric PM. (Pediatr Res 62: 291-294, 2007)

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

“…Adjuvant treatment with dexamethasone resulted in a reduction of hearing loss in rabbit and gerbil models of pneumococcal meningitis (235,406) but did not have a significant effect in infant rats (94). A recent meta-analysis of human trials evaluating adjuvant dexamethasone treatment suggested that dexamethasone may reduce hearing loss among survivors (499).…”

Oxidative Stress, Cytokine/Chemokine and Disruption of Blood–Brain Barrier in Neonate Rats After Meningitis by Streptococcus agalactiae

“…Evan 0 s blue was injected intra peritoneally (ip), 1 mL/1%, in each animal 1 h before being killed [8]. The experiments with animals were performed under anesthesia, consisting of an intraperitoneal administration of ketamine (6.6 mg/kg), xylazine (0.3 mg/ kg), and acepromazine (0.16 mg/kg) [22,23].…”

“…The incidence of S. agalactiae has declined in the United States from 1.7 cases to 0.34-0.37 cases per 1,000 live births in recent years [6]. However, GBS disease remains the leading infectious cause of morbidity and mortality among newborns in the United States [7,8].…”

Adjunctive Daptomycin Attenuates Brain Damage and Hearing Loss More Efficiently than Rifampin in Infant Rat Pneumococcal Meningitis

“…In both autopsy studies of human victims of bacterial meningitis (48) and experimental models of pneumococcal meningitis (7,22,24,28), cortical necrosis and apoptotic cell death in the dentate gyrus of the hippocampus are reproducible histopathologic correlates of neurological damage. Furthermore, injury of neuronal and hair cells in the cochlea, as documented in experimental pneumococcal meningitis in rats (14,32), has been identified as a morphological correlate of hearing loss.…”