Advances in adjuvant therapy against acute bacterial meningitis.
Death and co-morbidity derived from acute bacterial meningitis remain unacceptably high and are mainly related to immune-mediated cerebral dysfunction. Cerebral edema, hydrocephalus and ischaemic cerebrovascular events are severe complications that eventually occur following the activation of a complex network of cytokines, chemokines, proteases and oxidants released after cerebrospinal fluid infection. The caspase pathway appears to play a central role in the induction and amplification of the host inflammatory response. Such overactive immune reactions induce brain cell damage but, importantly, they may potentially be blocked. Several agents have been developed aiming to counteract the deleterious effects of such immune imbalance. These drugs are candidates to become adjuvant therapy against acute bacterial meningitis in the future, in addition to dexamethasone. We review the current state-of-art of bacterial meningitis adjuvant therapy, including caspase inhibitors, antioxidants, poly (ADP-ribose) polymerase inhibitors, inhibitors of lipid peroxidation and metalloproteinase inhibitors.
Pomar
Virginia
V
Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Av. Sant Antoni M Claret, 167, 08025 Barcelona, Spain. pdomingo@hsp.santpau.es
Martínez
Sergi
S
Paredes
Roger
R
Domingo
Pere
P
D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D061945:Caspase Inhibitors; D004359:Drug Therapy, Combination; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000473:pathology; D045726:Metalloproteases / Q000037:antagonists & inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D000975:Antioxidants; D061945:Caspase Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D045726:Metalloproteases