Pathogenesis of infections related to foreign devices within the cerebral ventricles

Sammanfattning: Coagulase-negative staphyloccoci (CoNS) are the most frequently isolated micro-organisms from infected cerebrospinal fluid (CSF) shunts and temporary ventricular drainage catheters, used in modern neurosurgery. CoNS originate from the skinflora of the patient or the surgeon and gain access to the surface of the implant at the insertion, but the infection can erupt up to a year later or more. Immediately after insertion host proteins are adsorbed to the surface of the implant. These are vitronectin (Vn), fibronectin, fibrinogen, thrombospondin, collagen, complement factors, coagulation factors and immunoglobulins. The CoNS express binding of these components, and several of them, have been shown to mediate bacterial adherence. The binding of a CoNS strain, BD 93 5703, from an infected CSF shunt to polymers exposed to human CSF was investigated. It was shown that CoNS adherence was lowered to CSF preexposed catheters. Anti-Vn antibodies could furthermore block the adhesion of the mentioned strain, but not of other strains tested. No other protein was shown to mediate staphylococcal adhesion in this thesis. The strain, which adhesion was dependent on Vn was shown to express four binding proteins in its cell wall. Of these four proteins, from 16, 21, 38 and 52 kDa molecular weights, the 52 kDa protein had the highest affinity for Vn. Complement activation is a complication to insertion of implants in contact with blood. Vn is known to inhibit the terminal complement complex, C5b-9, of the complement system, by forming SC5b-9. Immobilized Vn was shown to retain this function. Vn-binding CoNS could block the formation of SC5b-9, letting the complement activation go on as if no Vn was present. Vn and terminal complement complex were shown to be present in CSF and on removed CSF shunts. The level of Vn was higher in pathological than in normal CSF, due to plasma leakage into the CSF. Vn found on temporary catheters and shunts was identified as a dimer, which natural habitat is plasma. Dimeric Vn is not activated and its biological functions are intact. The Vn-binding in CoNS can thus have an important role in the pathogenesis of CSF shunt infections. It can mediate adhesion to the shunt surface and it can also block the inhibitory effect of Vn on the complement system.