Meningitis in Neonates: Bench to Bedside

Matrix Metalloproteinase Inhibition Lowers Mortality and Brain Injury in Experimental Pneumococcal Meningitis

“…A marked increase in the number of apoptotic cells in the hippocampal DG, caused by an overwhelming immune response and bacterial toxins without direct exposure of the DG to pneumococci, is first observed between 18 and 24 hpi (37,40,43). In experimental PM, the mortality rate is highest between 21 and 29 hpi, when inflammation peaks because of bacteriolysis after the application of ceftriaxone, among other factors (28,44). Therefore, potential pharmacologic interventions, including MMP and TACE inhibition, have to fall before or within this time window to be effective.…”

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

“…Matrix metalloproteinase inhibition, reduction of reactive oxygen species by antioxidants, and inhibiting mediators of apoptosis are possible candidates for inhibiting host immune reaction in bacterial meningitis (25). In clinical practice, only adjuvant use of the antiinflammatory corticosteroid dexamethasone has been shown to be beneficial in adults with bacterial meningitis (4,11) and in childhood meningitis caused by Haemophilus influenzae type b (38,49), a pathogen that has virtually been eradicated in global regions that have implemented the corresponding vaccination.…”

“…In our current understanding of the pathophysiology of pneumococcal meningitis, the host-mediated immune response, triggered by subcapsular components of bacteria, contributes substantially to brain damage (25,34,63). Bacterial components are recognized by membrane-bound host cell receptors, such as TLR2 and TLR4 (3,33).…”

Early onset meningococcal meningitis

“…1 These protective antibodies are found in an estimated 50% of neonates at birth and decline from the sixth month of life. 1,6 Since most protective antibodies are transferred to the foetus during the third trimester of pregnancy, it follows that premature infants are more likely to develop N. meningitidis septicaemia in the neonatal period. An important point to consider is that complement-mediated phagocytosis is one of the critical defences against infection with N. meningitidis, a process that is impaired in neonates because of various factors.…”

“…However, data on bacterial meningitis (including N. meningitidis) in the neonatal period have shown that these neonates have a 16-fold increase in risk of serious disability compared with matched controls. 6 In our infant, there was evidence of multiple cerebral infarcts and neurological sequelae, with seizures, tone disturbance and possible visual impairment.…”