Meningitis‐associated hearing loss: Protection by adjunctive antioxidant therapy

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Abstract
Hearing loss is the most frequent long‐term complication of pneumococcal meningitis, affecting up to 40% of survivors. Unfortunately, adjuvant therapy with dexamethasone has failed to satisfactorily reduce its incidence. Therefore, we evaluated the use of antioxidants for the adjunctive therapy of meningitis‐associated deafness. Eighteen hours after intracisternal injection of 7.5 × 105 colony‐forming units of Streptococcus pneumoniae, rats were treated systemically either with ceftriaxone and the antioxidants and peroxynitrite scavengers Mn(III)tetrakis(4‐benzoic acid)‐porphyrin (MnTBAP) or N‐acetyl‐L‐cysteine (NAC) or placebo (1ml phosphate‐buffered saline) for 4 days. Hearing was assessed by auditory brainstem response audiometry. Adjunctive antioxidant therapy significantly reduced the long‐term hearing loss (14 days after infection) for square wave impulses (mean hearing loss ± SD: ceftriaxone and placebo, 45±26dB; ceftriaxone and MnTBAP, 9±23dB; ceftriaxone and NAC, 19±30dB) as well as 1kHz (ceftriaxone and placebo, 28±19dB; ceftriaxone and MnTBAP, 10±16dB; ceftriaxone and NAC, 10±17dB), and 10kHz tone bursts (ceftriaxone and placebo, 62±27dB; ceftriaxone and MnTBAP, 16±13dB; ceftriaxone and NAC, 25±26dB). Furthermore, both antioxidants attenuated the morphological correlates of meningogenic hearing loss, namely, long‐term blood‐labyrinth barrier disruption, spiral ganglion neuronal loss, and fibrous obliteration of the perilymphatic spaces. Adjuvant antioxidant therapy is highly otoprotective in meningitis and therefore is a promising future treatment option.