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

Baystson, Roger; Ashraf, Waheed; Pelegrin, Ivan; Fowkes, Katherine; Bienemann, Alison S.; Singleton, William G.B.; Scott, Ian S.

Abstract

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. 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 1 week or 4 weeks, 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 4 week 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 4 weeks, 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.

Citation

Baystson, R., Ashraf, W., Pelegrin, I., Fowkes, K., Bienemann, A. S., Singleton, W. G., & Scott, I. S. (2019). An external ventricular drainage catheter impregnated with rifampicin, trimethoprim and triclosan, with extended activity against multi-drug-resistant Gram negative bacteria: an in vitro and in vivo study. Journal of Antimicrobial Chemotherapy, 74(10), 2959-2964. https://doi.org/10.1093/jac/dkz293

• Journal Article Type: Article
• Acceptance Date: Jun 11, 2019
• Online Publication Date: Jul 13, 2019
• Publication Date: Jul 13, 2019
• Deposit Date: Jun 11, 2019
• Publicly Available Date: Aug 5, 2019
• Journal: Journal of Antimicrobial Chemotherapy
• Print ISSN: 0305-7453
• Electronic ISSN: 1460-2091
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 74
• Issue: 10
• Pages: 2959-2964
• DOI: https://doi.org/10.1093/jac/dkz293
• Keywords: Pharmacology (medical); Pharmacology; Infectious Diseases
• Public URL: https://nottingham-repository.worktribe.com/output/2175789
• Publisher URL: https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkz293/5532147