An external ventricular drainage catheter impregnated with rifampicin, trimethoprim and triclosan, with extended activity against MDR Gram-negative bacteria: an in vitro and in vivo study

Abstract

Background: External ventricular drainage (EVD) carries a high risk of ventriculitis, increasingly caused by MDR Gram-negative bacteria such as Escherichia coli and Acinetobacter baumannii. Existing antimicrobial EVD catheters are not effective against these, and we have developed a catheter with activity against MDR bacteria and demonstrated the safety of the new formulation for use in the brain. Objectives: Our aim was to determine the ability of a newly formulated impregnated EVD catheters to withstand challenge with MDR Gram-negative bacteria and to obtain information about its safety for use in the CNS. Methods: Catheters impregnated with three antimicrobials (rifampicin, trimethoprim and triclosan) were challenged in flow conditions at four weekly timepoints with high doses of MDR bacteria, including MRSA and Acinetobacter, and monitored for bacterial colonization. Catheter segments were also inserted intracerebrally into Wistar rats, which were monitored for clinical and behavioural change, and weight loss. Brains were removed after either 1week or 4weeks, and examined for evidence of inflammation and toxicity. Results: Control catheters colonized quickly after the first challenge, while no colonization occurred in the impregnated catheters even after the 4week challenge. Animals receiving the antimicrobial segments behaved normally and gained weight as expected. Neurohistochemistry revealed only surgical trauma and no evidence of neurotoxicity. Conclusions The antimicrobial catheter appears to withstand bacterial challenge for at least 4weeks, suggesting that it might offer protection against infection with MDR Gram-negative bacteria in patients undergoing EVD. It also appears to be safe for use in the CNS.