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.

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

doi:10.1093/jac/dkz293

Abstract

BackgroundExternal 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.ObjectivesOur 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.MethodsCatheters 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.ResultsControl 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.ConclusionsThe 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.

Highlights

External ventricular drainage (EVD) of CSF is widely used as a temporary measure in the management of raised intracranial pressure associated with a variety of conditions including trauma, haemorrhage, hydrocephalus, infection management and tumours
Control catheters challenged with 105 cfu/mL of the test bacteria colonized within a few days of inoculation, showing high bacterial counts (108 cfu/mL)
This has been confirmed by scanning electron microscopic examination of impregnated catheters after 4 weeks of perfusion and bacterial challenge (Figure 1a–c)

Summary

Introduction

External ventricular drainage (EVD) of CSF is widely used as a temporary measure in the management of raised intracranial pressure associated with a variety of conditions including trauma, haemorrhage, hydrocephalus, infection management and tumours. Many regimens have been proposed to reduce the rate of ventriculitis associated with EVD, ranging from antibiotic prophylaxis to ‘bundles’ of interventions. While the former shows some benefit, but a tendency to provoke resistance, bundles usually bring about a reduction in infection rates, but depend on sustained compliance, rates rising again after some time.[4] Some changes have brought about clear benefit, such as tunnelling of the catheter and restricting CSF aspiration to that clinically necessary. 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

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