Prophylactic Antibiotics Useful With Antibiotic Impregnated External Ventricular Drains (EVDs)?

Montefiore Medicine Academic Health System

Status and phase: Enrolling; Phase 1

Conditions: Hydrocephalus; Subarachnoid Hemorrhage; Ventriculitis, Cerebral; Intracerebral Hemorrhage

Treatments: Drug: Long term (continuous) prophylactic antibiotics; Drug: 24 hours antibiotics

Study type: Interventional

Funder types: Other

Identifiers

NCT05001750

2021-12680

Details and patient eligibility

About

The principal objective of this study is to compare the incidence of ventriculostomy related infections (VRIs) in patients who receive twenty-four hours of antibiotics, beginning no more than sixty minutes prior to EVD placement, to the incidence of VRIs in patients who also receive a pre-procedural dose of antibiotics with continued dosing of antibiotics for the duration of the external ventricular drain (EVD). At this time, the duration of prophylactic antibiotic use with antibiotic impregnated EVDs is unknown.

Full description

Intracranial hemorrhage (ICH), which include subarachnoid hemorrhage (SAH), intraparenchymal hemorrhage (IPH) and intraventricular hemorrhage (IVH) affects nearly 30,000 every year in US alone. Despite rapid advances in treatment of just one of these pathologies, SAH, the case fatality rate remains at 32.2% in US. Successful post interventional outcome of patients suffering from SAH depends on the management of a multitude of secondary neurological complications, including prevention of re-hemorrhage, vasospasm, hydrocephalus, increased intracranial pressure (ICP), and seizure. A major component of this care is placement of an external ventricular drain (EVD), which is routine in patients suffering from SAH to manage ICP and to treat hydrocephalus.

Placement of an EVD, however, is not without risk, in particular with regards to infection, commonly referred to as Ventriculostomy Related Infection (VRI). The rate of VRIs has been reported to range widely from 0% to 40% however, with an increased risk in patients suffering from hemorrhage or any vascular diseases (28.6%) in this subgroup, while typically lower (18.5%) in patients suffering from other neurosurgical diagnoses.

Ventriculostomy related infections have been associated with increased delayed cerebral ischemia (a.k.a.; vasospasm), extended hospital duration, increased mortality and higher hospital costs. Despite the importance of management and prevention of VRIs, there hasn't been any clear consensus on administration of antibiotics post-procedurally. This is perpetuated by the fact that each institution, and even providers within institutions, have varying definitions of VRIs, and their own protocols regarding administration of antibiotics.

Although there is an established protocol for insertion of EVD, which include pre-procedural intravenous antibiotic administration, there is no consensus on duration of post-operative antibiotics, despite the fact that successful patient outcomes depend on management of these VRIs.

Further complicating the problem is the growing concern over increasing resistance to gram-positive organisms due to overuse of systemic antibiotics, as well as development of Clostridium difficile infection. As a result, practice is quite variable, based upon individual clinician preferences, rather than evidence based. Determining optimal strategies and protocols to minimize the incidence of VRI, while ensuring responsible antibiotic usage, thereby minimizing their deleterious effects on both individuals and communities, is of chief interest.

These universal concerns and questions deserve a new formal study in this initial feasibility study.

Enrollment: 84 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• patients over the age of 18 years
• patients diagnosed with a subarachnoid hemorrhage, intracerebral hemorrhage, or acute ischemic stroke who require an EVD for management of their underlying condition. In certain cases (a small minority), an EVD must be replaced due to failure (i.e., blood clot interrupting flow). In such cases, patients will be re-dosed with antibiotics prior to catheter exchange in typical fashion and continue in their previously randomized treatment group

Exclusion criteria

• patients who were on antibiotics within the week prior to admission
• patients with leukopenia (<5000) at baseline
• patients with signs of meningitis, ventriculitis or any other infection at presentation
• patients who are pregnant or prisoners
• patients aged < 18 years old

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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84 participants in 2 patient groups

Continuous antibiotic use until the EVD is removed

Experimental group

Description:

Continuous prophylactic antibiotic use until the EVD is removed. Antibiotics will begin no more than sixty minutes pre-procedure.

Treatment:

Drug: Long term (continuous) prophylactic antibiotics

Antibiotics for a total of twenty-four hours

Experimental group

Description:

Antibiotics for a total of twenty-four hours. Antibiotics will begin no more than sixty minutes pre-procedure.

Treatment:

Drug: 24 hours antibiotics