**7. Clinical studies**

#### **7.1 Surface-modified neurosurgical materials and devices**

A silicone shunt catheter made from expanded polytetrafluoroethylene (e-PTFE) has been evaluated but failed due to its porosity allowing tissue ingrowth [61].

PVP-coated catheters have been commercialised (Bioglide, Medtronic, USA). They need to be handled carefully when dry to prevent cracking of the coating, and must be soaked and rehydrated for use. This gives the opportunity for the surgeon to add antibiotics such as vancomycin or bacitracin to the soak saline, with the intention that it will add antimicrobial activity to the hydrophilic anti-attachment surface. Kaufmann et al. [62] carried out a clinical trial of commercially available PVP-coated shunts pre-soaked in bacitracin and found no effect on infection rates (p > 0.24). According to the authors, the concentration of bacitracin was not expected to be sufficient to affect infection risk, and reliance was mainly on the hydrogel, but is has been common practice to soak shunt and EVD catheters in antibiotic solution. However, in vitro studies have not shown an advantage of antibiotic soaking of PVP catheters [30, 31] and this was the case even when high concentrations of various antibiotics were tested [32]. An increase in shunt infection when PVP catheters were used was observed in another study by Kestle et al. [63] though no details were given on antibiotic soaking. In this study, a clearly higher infection risk was seen with PVP catheters (OR 1.91, CI 1.19–3.05, p = 0.007). While the lack of PVP coating in the catheter lumen might have been a factor in failure to prevent infection, the higher risk of infection in PVP-coated catheters compared to plain catheters remains unexplained.

#### **7.2 Antimicrobial coatings**

Silver-processed shunt and EVD catheters have been the subject of several clinical studies. An insignificant reduction (2.7% vs. 4.7%) was reported by Fichtner et al. [64] from a retrospective cohort study, while Lackner et al. [65] reported a statistically significant reduction in EVD infections (25–0%) in a mixed retrospective/ prospective cohort study with small numbers. A retrospective study comparing three

different types of polyurethane catheters, one of which was silver-processed, found a significant difference in infection rates between two non-silver catheters, both from different manufacturers, for unexplained reasons, but there was no significant difference in infection rates between the two polyurethane catheters (one containing silver) each from the same manufacturer [66]. This study would seem to indicate a difference in infection risk between two types of polyurethane catheter rather than any effect of silver, contrary to the claim in the title. A meta-analysis [67] found no significant overall reduction in EVD infection rate when silver-processed catheters were used, but they commented that their effect may be selective: a significantly lower rate of infection due to gram positive, but not gram negative, bacteria was found in the silver catheter groups. However, despite this, a large randomised controlled clinical trial of silver-processed EVD found a reduction in infection rate from 21.4 to 12.3% (13). The very high rate of infection in the plain catheter arm is unusual in UK, and the rate of 12.3% is still much higher than the 9.3% in most UK and Irish centres [68], though the authors state that they chose high-risk patients for their trial. A multicentre survey of EVD infections in UK and Ireland [68] found a higher infection rate (13.7%) in silver -processed catheters than in plain catheters (7.4%) but this did not reach statistical significance. Another randomised controlled trial of silver-processed catheters in CSF shunting failed to find any difference between plain and silver-processed arms [69] and this is consistent with studies of such catheters in other fields [70–72]. It is important to note that the precise nature of the silver -processing differs between studies, and this might affect the results.
