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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Long term (continuous) prophylactic antibiotics
  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. Nafcillin 1-2 grams every 6 hours (depending on weight) until the EVD is removed. If penicillin allergic, Doxycycline 100mg every 12 hours until the EVD is removed.
• Препарат 24 hours antibiotics
  Nafcillin 1-2 grams every 6 hours (depending on weight) for a total of 24 hours. If penicillin allergic, Doxycycline 100mg every 12 hours for a total of 24 hours.

Первичные конечные точки

• Number of Participants with Cerebrospinal Fluid Positive (CSF+) VRI [Срок оценки: From EVD insertion until discharge - estimated period of time is 2 weeks]

Вторичные конечные точки (6)

• Class of infecting organism [Срок оценки: From EVD insertion until discharge - estimated period of time is 2 weeks]
• Time to infection [Срок оценки: From EVD insertion until discharge - estimated period of time is 2 weeks]
• Number of attempts at EVD catheter insertion [Срок оценки: From EVD insertion until discharge - estimated period of time is 2 weeks]
• Incidence of nosocomial infections [Срок оценки: From EVD insertion until discharge - estimated period of time is 2 weeks]
• Overall Morbidity [Срок оценки: From EVD insertion until discharge - estimated period of time is 2 weeks]
• Overall Mortality [Срок оценки: From EVD insertion until discharge - estimated period of time is 2 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Montefiore Medical Center — The Bronx

Публикации

• Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol. 2009 Jul;8(7):635-42. doi: 10.1016/S1474-4422(09)70126-7. Epub 2009 Jun 6. PMID 19501022
• Lozier AP, Sciacca RR, Romagnoli MF, Connolly ES Jr. Ventriculostomy-related infections: a critical review of the literature. Neurosurgery. 2002 Jul;51(1):170-81; discussion 181-2. doi: 10.1097/00006123-200207000-00024. PMID 12182415
• Foreman PM, Chua M, Harrigan MR, Fisher WS 3rd, Vyas NA, Lipsky RH, Walters BC, Tubbs RS, Shoja MM, Griessenauer CJ. Association of nosocomial infections with delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage. J Neurosurg. 2016 Dec;125(6):1383-1389. doi: 10.3171/2015.10.JNS151959. Epub 2016 Feb 12. PMID 26871202
• Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE, Badjatia N, Parra A, Connolly ES, Mayer SA. Impact of nosocomial infectious complications after subarachnoid hemorrhage. Neurosurgery. 2008 Jan;62(1):80-7; discussion 87. doi: 10.1227/01.NEU.0000311064.18368.EA. PMID 18300894
• Lyke KE, Obasanjo OO, Williams MA, O'Brien M, Chotani R, Perl TM. Ventriculitis complicating use of intraventricular catheters in adult neurosurgical patients. Clin Infect Dis. 2001 Dec 15;33(12):2028-33. doi: 10.1086/324492. Epub 2001 Nov 9. PMID 11712094
• Aucoin PJ, Kotilainen HR, Gantz NM, Davidson R, Kellogg P, Stone B. Intracranial pressure monitors. Epidemiologic study of risk factors and infections. Am J Med. 1986 Mar;80(3):369-76. doi: 10.1016/0002-9343(86)90708-4. PMID 3953614
• Mayhall CG, Archer NH, Lamb VA, Spadora AC, Baggett JW, Ward JD, Narayan RK. Ventriculostomy-related infections. A prospective epidemiologic study. N Engl J Med. 1984 Mar 1;310(9):553-9. doi: 10.1056/NEJM198403013100903. PMID 6694707
• Wong GK, Poon WW. Ventriculostomy infections. J Neurosurg. 2006 Sep;105(3):506-7; author reply 507. doi: 10.3171/jns.2006.105.3.506. No abstract available. PMID 16961156

Идентификаторы

NCT: NCT05001750 · 2021-12680

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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