**6. Activity of impregnated EVD catheters against multi-drug-resistant pathogens**

Though the Ventriclear EVD catheter contains minocycline, neither this nor Bactiseal catheters are likely to have any useful effect against gram negative EVD pathogens. These include not only *E coli* and *Klebsiella pneumoniae*, but multi-drugresistant (MDR) strains of these as well as intrinsically MDR bacteria such as *A baumannii*. A catheter with activity against these pathogens is badly needed. The catheter containing trimethoprim developed by Kohnen et al. [50] might have some activity against *E coli* and *K pneumoniae* (unless MDR) but these were not tested. A later development by the same authors, containing sparfloxacin, would probably show better anti-gram negative activity, but again they did not test this [51]. An EVD catheter impregnated with rifampicin, trimethoprim and triclosan, using the impregnation method previously described [44] has been tested in vitro [58]. The antimicrobials were again chosen to provide broad spectrum of activity against EVD pathogens, to reduce the risk of resistance developing (Dual Drug Principle) and for compatibility with the impregnation technology. The impregnated catheters were installed in a modular longterm flow apparatus and perfused constantly with nutrient medium. Both plain and impregnated catheters were challenged weekly with suspensions of test bacteria (105 cfu/mL) and monitored for colonisation. Plain catheters all colonised within 24-48 hr., but none of the impregnated catheters colonised. The 17 test bacteria consisted of clinical isolates of *E coli* (including ESBL and NDM-1 producers), *Enterobacter cloacae*, *Klebsiella pneumoniae*, methicillin-resistant *Staphylococcus aureus* (MRSA) and *S epidermidis* (MRSE), and *A baumannii*. Also included was a series of 5 isolates of *S epidermidis* from Bactiseal shunt infections due to intrinsic resistance to either rifampicin or clindamycin, or both. Catheter segments were inserted stereotactically into the frontal lobes of rats

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

and the brains examined after either 1 week or 4 weeks for signs of neurotoxicity. Behavioural changes and weight gain in the rats was also monitored. All rats gained weight normally and did not show any behavioural anomalies. Neurohistochemical examination showed significant glial response in both control and impregnated segments after 1 week, considered to be due to surgical trauma, and this had subsided by week 4. The findings suggest that this EVD catheter might address the remaining problem of antimicrobial activity against MDR EVD pathogens including *A baumannii*. The catheter has not yet been commercialised. The same impregnation method was used to produce an EVD catheter containing rifampicin, clindamycin and trimethoprim [59]. The catheters were tested by the Serial Plate Transfer test (SPTT) [44, 60], which is useful as a screening test but does not dispense with the need for more rigorous clinically predictive tests. As expected, the catheter showed prolonged activity against *S epidermidis*, but not MRSA, in the SPTT. Animal inoculation was carried out by subcutaneous implantation to test for biocompatibility, but no implantation into the central nervous system was done.
