**7.3 Antimicrobial impregnation**

The first technology for impregnation of silicone catheters with antimicrobials was published in 1989 [44]. This technology, resulting in a CSF shunt containing relatively small concentrations of rifampicin and clindamycin, was the subject of numerous clinical studies. The first was a prospective randomised study of 110 patients [73]. The infection rates were 6% in the impregnated group and 17% in the plain control group. Importantly all the infections were due to staphylococci in the control group, and there were no staphylococcal infections in the impregnated group. Of the three infected patients in the "impregnated" group, all had gram negative infections and one was also infected with HIV. In another study with historical controls, there were seven infections (15%) in the plain catheter group, and one (3%) in the "impregnated" group [74]. This was a child who scratched open the abdominal wound in the postoperative period, and contaminated the shunt with *S aureus*. In another study, again with historical controls, there were three shunt infections (1.2%) in the antimicrobial catheter group and 36 (6.5%) in the preceding plain catheter group (p = 0.0015) [75]. Of the three infections in the "impregnated" group, two were due to *S epidermidis*, both susceptible to rifampicin and clindamycin, and in one case the clinical course was complicated by EVD, reservoir placement and shunt revision for intraventricular haemorrage before the infection occurred. The third case was due to *Haemophilus influenzae* 8 months postoperatively. *H influenzae* was, at the time, a common cause of childhood community—acquired meningitis. The antimicrobial activity of the shunt would probably have declined by that time and in any case would not have been very effective against this bacterium. A retrospective study in children, again with historical controls, showed a statistically non-significant reduction in shunt infection (7 vs. 4 infections, p = 0.534). Two of the 4 infections in the antimicrobial catheter group were due to gram negative bacilli and only one was

#### *Infections in Intracranial Pressure Management: Impact of New Technologies on Infection Rates DOI: http://dx.doi.org/10.5772/intechopen.110349*

due to *S epidermidis*. In the control group, four infections were due to *S epidermidis*. The authors concluded on this basis that there was no evidence of efficacy of antimicrobial shunt catheters [76]. A multicentre study in children, again with historical controls, had considerable problems with differences in results between centres, but concluded that antimicrobial shunt catheters might significantly reduce infection rates in paediatrics, but that a randomised controlled trial was needed [77]. An observational study [78] found no significant difference in shunt infection rates between antimicrobial and plain catheters. However, there were additional postoperative risk factors, such as further neurosurgical intervention, and the diagnostic criteria included late ulceration over the shunt in three of the five infections in the antimicrobial catheter group, leading to non-surgical shunt infection which, as the authors say, the antimicrobial shunt could not be expected to prevent. A systematic review found a significant reduction in shunt infection rate for antimicrobial catheters (RR 0.42, 95% CI 0.32–0.55) [79]. A retrospective review of VP shunts in high-risk children, defined as premature when shunted, post-meningitic, post shunt infection, or having undergone EVD, found a statistically significant reduction in infection in all these groups [80]. The reduction from 20 to 5.5% in the high-risk neonate group was also found by Hayhurst et al. [81] Parker also recorded the lack of adverse effects in this vulnerable group [81]. Their finding of a reduction in the group where EVD had been used was interesting, as others had suggested that this might have increased the risk of failure of the antimicrobial catheters. All of these studies used the rifampicin + clindamycin impregnated shunt. None of them was a randomised controlled trial and in many cases such a study was called for in the conclusions. There is a formal registry of CSF shunting in UK, based in Cambridge, and a report issued in 2009 on almost 2000 matched impregnated / plain cases showed a reduction from 4.7 to 3%, which just reached statistical significance (p = 0.048) [82]. However, there were limitations such as reporting bias, and use of an intention—to—treat analysis as well as very different rates and criteria from contributing institutions. Eventually, a formal multicentre randomised controlled trial, the BASICS study, was carried out, comparing plain shunts with silver-processed and antimicrobial impregnated ones in 1594 patients [69]. After a median follow-up of 22 months (IQR 10–24), the infection rates were 6% in both plain and silver-processed groups, and 2% in the antimicrobial impregnated group (p = 0.0038). This finding confirmed most of the previous retrospective or historically-controlled studies. Even before this definitive study, there had been a steady increase in uptake of antimicrobial-impregnated shunts in UK, so that since their introduction in 2001 they were used in approximately 70% of shunt surgeries in 2014 [83]. This seems to have been matched by a steady decline in shunt infection rates over this period.

#### **7.4 Cost-effectiveness studies**

The BASICS study raised the issue of healthcare cost savings based on reduction of treatment costs for infection. This had been addressed by Sciubba et al. who speculated that shorter hospital stay (30 vs. 17 days) and reduced adverse events due to treatment of shunt infection might lead to significant cost savings [84]. A German study found a cost saving of \$17,300 in children and \$13,000 in adults in those receiving antimicrobial -impregnated shunts compared to plain shunts [85]. An American study found that the hospital cost per 100 patients shunted was \$151,582 and \$593,715 for antimicrobial and plain shunts respectively, due to reduction in costs of treatment of infection [86]. In a meta-analysis and cost study, it was found

that, assuming 200 shunt operations per year, annual costs savings would range from \$90,000 to \$1.3 M in American centres [87]. The use of shunt catheters impregnated with rifampicin and clindamycin appears to reduce the incidence of shunt infection and by so doing, reduce healthcare costs very significantly. The benefit for patients and their relatives is also therefore obvious, with less morbidity, fewer shunt revisions for infection, and less time spent in hospital.
