Effect of vancomycin versus rifampicin in combination with ceftriaxone on inflammation and hearing loss in experimental pneumococcal meningitis

Abstract number: P1923

Wittwer M., Rohrbach J., Aebi C., Leib S.L.

Background: Up to 30% of survivors of bacterial meningitis (BM) suffer from persisting hearing loss (>90dB) due to damage to the inner ear. Vancomycin has become an important antibacterial treatment option for BM due to its efficacy against Streptococcus pneumoniae strains that are resistant to other antibiotics. However recent studies reported increased ototoxic effects of vancomycin combined with ceftriaxone in BM.

Aims: In the presented study we assessed the effect of combination therapies of ceftriaxone with either vancomycin or rifampicin on cytokine levels in the cerebrospinal fluid (CSF) 6 h after initiation of antibiotic therapy and at 21 days after infection we assessed the incidence and extent of hearing loss by auditory brain stem response (ABR) and neuronal density in the spiral ganglion of the inner ear.

Methods: Eleven days old Wistar rats (n = 46) were injected intracisternally with 10ml saline containing 2×106 cfu/ml S. pneumoniae (serogroup 3) or sterile saline as controls (n = 10). CSF was obtained by puncture of the cisterna magna to document infection at 18 h after infection and to assess cytokine levels at 24 h after infection. Antibiotic treatment was initiated 18 h after infection. Rats were randomised for 10 days treatment with either vancomycin (60 mg/kg i.p.; bid) in combination with ceftriaxone (100 mg/ml s.c.; bid) or for treatment with rifampicin (20 mg/kg i.p.; bid) in combination with ceftriaxone. Twenty days after infection ABR was measured, animals were sacrificed and both cochleae processed for histomorphometry.

Results: All infected animals showed increased CSF concentrations of IFN-gamma, TNF-alpha, IL-1alpha, IL-1beta, IL-6 and IL-10. Of all infected animals 94% demonstrated a significant hearing loss (P < 0.0001, compared to mock infection). Neuronal density between 1882 and 1099 cells /mm2 was associated with normal hearing capacity. Hearing started to decline at a neuronal density of 1052 cells/mm2 and below 746 cells /mm2 rats were functionally deaf. Combination of ceftriaxone with vancomycin vs. ceftriaxone with rifampicin did not result in significant differences between the two treatment groups for all parameters evaluated.

Conclusions: The combination of vancomycin plus ceftriaxone versus rifampicin plus ceftriaxone for therapy of experimental pneumococcal meningitis did not produce significant differences in CSF inflammation and the incidence and severity of hearing loss.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Location: Barcelona, Spain
Presentation type:
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