Protection of blood brain barrier integrity and modulation of inflammatory mediators during treatment of pneumococcal meningitis with daptomycin or ceftriaxone.

Pneumococcal meningitis is associated with neurologic sequelae, such as learning and memory impairment. Most recently, a nonbacteriolytic antibiotic has been investigated to minimise the inflammatory host response and prevent cognitive damage. In this study, we compared daptomycin (DPTO) or ceftriaxone (CFX) treatment on the inflammatory parameters and on the blood-brain barrier (BBB) integrity in experimental pneumococcal meningitis. In the first experiment, the animals received 10 µl of a Streptococcus pneumoniae suspension or artificial cerebrospinal fluid by intracerebroventricular (i.c.v.) and were treated with CFX or DPTO at 18 h post-infection. The animals were euthanised at 18, 20, 24, 36 and 40 h post-infection. In the hippocampus, brain-derived neurotrophic factor (BDNF), tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and IL-10 levels were not different between treatment groups; however, IL-4 and cytokine-induced neutrophil chemoattractant 1 (CINC-1) levels decreased in the CFX group. In the frontal cortex, TNF-α, IL- 4, IL-6, IL-10 and BDNF levels were not different between treatment groups. Only CINC-1 levels decreased at 40 h postinfection with CFX treatment. In the second experiment, the animals received DPTO or CFX for 7 days and were euthanised 10 days after pneumococcal meningitis induction. TNF-α, IL-6, IL-10, CINC-1 and BDNF levels were not different between treatment groups in the hippocampus; however, IL-4 levels decreased in CFX group. In the third experiment, the animals received 10 µl of an S. pneumoniae suspension or artificial CSF by i.c.v. and were treated with a single dose of CFX or DTPO antibiotic; assessment of the BBB breakdown showed that both antibiotics prevented the BBB disruption. Both treatments equally protected the BBB integrity, and there were no significant difference in cytokine production.

Attenuation of cognitive impairment by the nonbacteriolytic antibiotic daptomycin in Wistar rats submitted to pneumococcal meningitis.

BACKGROUND: Streptococcus pneumoniae is associated with neurologic sequels, such as, seizures, sensory-motor deficits, hearing loss, learning and memory impairment, which can occur in approximately 30 to 52% of surviving patients. Neuronal damage can be caused by intense inflammatory reaction and direct effects of the bacteria virulence factors. The aim of the present study was to evaluate the effects of the nonbacteriolytic antibiotic daptomycin versus ceftriaxone on behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. RESULTS: Ten days after induction we verified that the meningitis group with daptomycin treatment showed retention of aversive memory; it presented memory of the object recognition at short term and long term. In continuous multiple-trials step-down inhibitory avoidance task the meningitis group with ceftriaxone treatment required approximately two times more stimulus to reach the acquisition criterion when compared with meningitis group with daptomycin treatment. However, in the habituation memory test there were no differences in the number of crossings and rearings in training and task sessions demonstrating habituation impairment to the environment task in both meningitis groups. CONCLUSIONS: The evidence of the present study shows the potential alternative of the treatment with daptomycin in preventing learning and memory impairments caused by pneumococcal meningitis. Further investigations are necessary to provide support for evaluation of daptomycin as an alternative treatment of bacterial meningitis.