Early Diagnosis of Native and Device-associated Meningitis

NCT05146570 | Unknown

• 1 other identifier: DIAMEN
• Study Type: interventional
• Target: 842
• Locations: 1 country
• Sites: 1

Brief Summary

Device-associated meningitis is a severe complication after implantation of various central nervous system (CNS) devices such as ventriculoperitoneal (VP) and ventriculoatrial (VA) shunts, external ventricular drains (EVD), lumbar drains (ELD) and intrathecal pumps. In contrast to native meningitis, these infections are hard to diagnose both clinically and on the laboratory basis due to (i) atypical clinical manifestation, (ii) overlapping inflammation following surgery, and (iii) common culture negativity due to previous antibiotic therapy and slow growth of low-virulent pathogens. Also, device-associated infections are difficult to differentiate from aseptic shunt failure (dysfunction) or "chemical meningitis" caused by underlying neurosurgical condition that prompted the placement of the CNS device (e.g. intracranial hemorrhage). Both native and device-associated meningitis carry substantial morbidity and mortality. Rapid and reliable diagnosis of meningitis is critical for initiating and choosing optimal treatment and minimizing the brain damage. Since treatment is different in septic than aseptic meningitis, it is paramount to diagnose or exclude septic meningitis as soon as possible. Several new diagnostic methods, such as cerebrospinal fluid (CSF) procalcitonin, interleukin-6 and polymerase chain reaction (PCR) have been proposed for rapid diagnosis of meningitis. However, insufficient sensitivity and/or specificity, long time until test result, and complexity in handling or interpretation of results limit their use in clinical routine. In previous studies CSF D-lactate test showed good specificity and sensitivity in patients with native meningitis. This biomarker is pathogen-specific - in contrast to other currently used host-specific biomarkers (leukocyte count, L-lactate, procalcitonin). However, no study on effectiveness of D-lactate test for the diagnosis of device-associated meningitis has been performed. Successful management of device-associated meningitis depends upon appropriate control of the infectious complications. To deal with such complications, adequate assessment and prediction of the clinical course are needed. Another use of D-lactate test could be his role as prognostic factor of the clinical course of device-associated meningitis.

Conditions

Bacterial Meningitis; Fungal Meningitis; Implant Infection

Keywords

Pathogen-specific diagnostic biomarker; Cerebrospinal fluid; D-lactate; Device-associated meningitis; Diagnosis of meningitis

Outcome Measures

Primary Outcomes (1)

• Performance of D-lactate test for the diagnosis of native and device-associated meningitis.

  Determined performance (D-lactate cut-off value, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio) of D-lactate test. * The Mann-Whitney test and Spearman's correlation will be applied to analyze the quantitative variables. Youden's J statistic will be used for determining optimal D-lactate cut-off value on the receiver operating characteristic (ROC) curve by maximizing sensitivity and specificity. * The area under the ROC curves will be calculated to compare the D-lactate test performance.

  up to 30 months

Secondary Outcomes (2)

• Performance of the D-lactate test in comparison with standard tests for the diagnosis of native and device-associated meningitis.

  up to 30 months

• Treatment monitoring using D-lactate test (as a predictor of treatment success / failure).

  up to 30 months

Study Arms (2)

Aseptic Meningitis

EXPERIMENTAL

In all patients cerebrospinal (CSF) fluid will be aspirated following the routine diagnostic procedure. After aspiration CSF will be tested with standard diagnostic tests and experimental diagnostic test (D-lactate). Immediately after aspiration, 0.5-1 ml of cerebrospinal fluid will be transferred into each of the following vials: * native vial for conventional culture (agar plate \& broth) * EDTA vial for the determination of leukocyte count and differential * pediatric blood culture bottle (BacTec PedsPlus/F) * native vial for biomarker detection (D-Lactate)

Diagnostic Test: D-lactate test; Diagnostic Test: Standard diagnostic tests

Infective meningitis

EXPERIMENTAL

In all patients cerebrospinal (CSF) fluid will be aspirated following the routine diagnostic procedure. After aspiration CSF will be tested with standard diagnostic tests and experimental diagnostic test (D-lactate). Immediately after aspiration, 0.5-1 ml of cerebrospinal fluid will be transferred into each of the following vials: * native vial for conventional culture (agar plate \& broth) * EDTA vial for the determination of leukocyte count and differential * pediatric blood culture bottle (BacTec PedsPlus/F) * native vial for biomarker detection (D-Lactate)

Diagnostic Test: D-lactate test; Diagnostic Test: Standard diagnostic tests

Interventions

D-lactate test DIAGNOSTIC_TEST

In device-associated meningitis, CSF will be aspirated before, during or after surgery related to the device, according to the standard practice. Lumbar/ventricular punctures (pre-, intra- and/or postoperatively) and external ventricular (EVD) and lumbar drainage (ELD) aspiration will be performed by neurologist or neurosurgeon according to standardized aseptic techniques. In patients with native meningitis, CSF will be aspirated by lumbar puncture, according the standard practice. The D-lactate test will be performed using spectrophotometric enzyme assay according to the manufacturer's instructions (D-Lactate Colorimetric Assay).

Aseptic Meningitis; Infective meningitis

Standard diagnostic tests DIAGNOSTIC_TEST

In device-associated meningitis, CSF will be aspirated before, during or after surgery related to the device, according to the standard practice. Lumbar/ventricular punctures (pre-, intra- and/or postoperatively) and external ventricular (EVD) and lumbar drainage (ELD) aspiration will be performed by neurologist or neurosurgeon according to standardized aseptic techniques. In patients with native meningitis, CSF will be aspirated by lumbar puncture, according the standard practice. The standard diagnostic tests will be performed according to standard diagnostic laboratory instructions.

Aseptic Meningitis; Infective meningitis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with suspected (clinical, paraclinical or radiological) native or device-associated meningitis
• age \>18 years
• patient signs written consent to participate in the study

You may not qualify if:

• inability of the patient or family member to consent to the study
• time from puncture to laboratory evaluation\> 24 hours

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

RECRUITING

Related Publications (8)

• Hasbun R. Central Nervous System Device Infections. Curr Infect Dis Rep. 2016 Nov;18(11):34. doi: 10.1007/s11908-016-0541-x.

  PMID: 27686676 BACKGROUND

• van de Beek D, Drake JM, Tunkel AR. Nosocomial bacterial meningitis. N Engl J Med. 2010 Jan 14;362(2):146-54. doi: 10.1056/NEJMra0804573. No abstract available.

  PMID: 20071704 BACKGROUND

• Conen A, Walti LN, Merlo A, Fluckiger U, Battegay M, Trampuz A. Characteristics and treatment outcome of cerebrospinal fluid shunt-associated infections in adults: a retrospective analysis over an 11-year period. Clin Infect Dis. 2008 Jul 1;47(1):73-82. doi: 10.1086/588298.

  PMID: 18484878 BACKGROUND

• Banks JT, Bharara S, Tubbs RS, Wolff CL, Gillespie GY, Markert JM, Blount JP. Polymerase chain reaction for the rapid detection of cerebrospinal fluid shunt or ventriculostomy infections. Neurosurgery. 2005 Dec;57(6):1237-43; discussion 1237-43. doi: 10.1227/01.neu.0000186038.98817.72.

  PMID: 16331172 BACKGROUND

• Li Y, Zhang G, Ma R, Du Y, Zhang L, Li F, Fang F, Lv H, Wang Q, Zhang Y, Kang X. The diagnostic value of cerebrospinal fluids procalcitonin and lactate for the differential diagnosis of post-neurosurgical bacterial meningitis and aseptic meningitis. Clin Biochem. 2015 Jan;48(1-2):50-4. doi: 10.1016/j.clinbiochem.2014.10.007. Epub 2014 Oct 30.

  PMID: 25445228 BACKGROUND

• Chen Z, Wang Y, Zeng A, Chen L, Wu R, Chen B, Chen M, Bo J, Zhang H, Peng Q, Lu J, Meng QH. The clinical diagnostic significance of cerebrospinal fluid D-lactate for bacterial meningitis. Clin Chim Acta. 2012 Oct 9;413(19-20):1512-5. doi: 10.1016/j.cca.2012.06.018. Epub 2012 Jun 17.

  PMID: 22713513 BACKGROUND

• Walti LN, Conen A, Coward J, Jost GF, Trampuz A. Characteristics of infections associated with external ventricular drains of cerebrospinal fluid. J Infect. 2013 May;66(5):424-31. doi: 10.1016/j.jinf.2012.12.010. Epub 2013 Jan 9.

  PMID: 23313468 BACKGROUND

• Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008 Jun;36(5):309-32. doi: 10.1016/j.ajic.2008.03.002. No abstract available.

  PMID: 18538699 BACKGROUND

MeSH Terms

Conditions

Meningitis, Bacterial; Meningitis, Fungal

Condition Hierarchy (Ancestors)

Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases; Central Nervous System Fungal Infections; Mycoses

Study Officials

• Andrej Trampuz, PD Dr. med

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Svetlana Karbysheva

CONTACT

+49 30 450 652 435; svetlana.karbysheva@charite.de

Paula Morovic

CONTACT

+49 30 450 615 048; paula.morovic@charite.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med, Head of Septic Surgery Unit

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: December 7, 2021
• Study Start: June 1, 2021
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: December 7, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)