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On the diagnosis of external ventricular drain related infections - Incidence, biomarkers and microbiological methods

Widén, Johan LU (2024) In Lund university, Faculty of Medicine Doctoral Dissertation Series
Abstract (Swedish)
The external ventricular drain (EVD) is an important instrument in the management of neuro-intensive care patients through its ability to meassure intracranial pressure and to treat increased intracranial pressure by drainage of cerebrospinal fluid (CSF). However, EVDs are associated with the risk of external ventricular drain related infection (EVDRI). EVDRI diagnosis is challenging as symtoms and CSF biomarker alterations associated with infection are unspecific in neuro-intensive care patients and reported incidence rates of EVDRI varies widely.

We investigated the incidence and microbiological aetiology of EVDRI of patients with subarachnoid haemorrhage in a Swedish setting and estimated the incidence to 5.8% or 4.1 per 1000... (More)
The external ventricular drain (EVD) is an important instrument in the management of neuro-intensive care patients through its ability to meassure intracranial pressure and to treat increased intracranial pressure by drainage of cerebrospinal fluid (CSF). However, EVDs are associated with the risk of external ventricular drain related infection (EVDRI). EVDRI diagnosis is challenging as symtoms and CSF biomarker alterations associated with infection are unspecific in neuro-intensive care patients and reported incidence rates of EVDRI varies widely.

We investigated the incidence and microbiological aetiology of EVDRI of patients with subarachnoid haemorrhage in a Swedish setting and estimated the incidence to 5.8% or 4.1 per 1000 EVD days. However, over 40% of subjects received treatment for EVDRI. The majority of EVDRI’s were caused by coagulase-negative staphylococci (Paper I). The diagnostic performance of the neutrophil protein heparin-binding protein (HBP) was assesed as a CSF biomarker for EVDRI in a separate cohort of
neuro-intensive care patients. HBP was found to be significantly higher in EVDRI but with considerable overlap to non-EVDRI subjects, resulting in a limited sensitivity of 86% and a specificity 76% for EVDRI (Paper II). Furthermore, the performance of polymerase chain reaction (PCR) of the 16S rRNA gene for the diagnosis of EVDRI was evaluated. This method showed a good concordance to bacterial culture of CSF and the results could be used to direct decisions regarding antimicrobial therapy prior to culture results. Additionally. the results did not indicate that false negative CSF cultures are common in patients treated with an EVD (Paper III). Finally we attempted to characterise the CSF proteome of EVDRI with mass spectrometry. However, no individual proteins were differentially expressed between subjects with and without EVDRI, probably due to large heterogeity of the CSF proteome of neuro-ICU patients, related to their underlying condition.

In summary, this thesis explores different aspects of EVDRI diagnosis and highlights the need for improved diagnostic methods. The results imply that finding sensitive and specific biomarkers related to the host response will be challenging due to the heterogeneity of the CSF proteome, whereas improved microbiological methods could improve EVDRI diagnostics. (Less)
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author
supervisor
opponent
  • professor Andersen Østergaard, Christian, Statens Serum Institut, Copenhagen
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund university, Faculty of Medicine Doctoral Dissertation Series
issue
2024:141
pages
88 pages
publisher
Lund University, Faculty of Medicine
defense location
Belfragesalen, BMC D15, Klinikgatan 32 i Lund. Join by Zoom: https://lu-se.zoom.us/j/65554027435
defense date
2024-11-22 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-639-5
language
Swedish
LU publication?
yes
id
2e05017b-8b00-4e17-a9a3-52ad25ad7962
date added to LUP
2024-10-25 10:35:06
date last changed
2025-04-04 15:29:34
@phdthesis{2e05017b-8b00-4e17-a9a3-52ad25ad7962,
  abstract     = {{The external ventricular drain (EVD) is an important instrument in the management of neuro-intensive care patients through its ability to meassure intracranial pressure and to treat increased intracranial pressure by drainage of cerebrospinal fluid (CSF). However, EVDs are associated with the risk of external ventricular drain related infection (EVDRI). EVDRI diagnosis is challenging as symtoms and CSF biomarker alterations associated with infection are unspecific in neuro-intensive care patients and reported incidence rates of EVDRI varies widely.<br/><br/>We investigated the incidence and microbiological aetiology of EVDRI of patients with subarachnoid haemorrhage in a Swedish setting and estimated the incidence to 5.8% or 4.1 per 1000 EVD days. However, over 40% of subjects received treatment for EVDRI. The majority of EVDRI’s were caused by coagulase-negative staphylococci (Paper I). The diagnostic performance of the neutrophil protein heparin-binding protein (HBP) was assesed as a CSF biomarker for EVDRI in a separate cohort of<br/>neuro-intensive care patients. HBP was found to be significantly higher in EVDRI but with considerable overlap to non-EVDRI subjects, resulting in a limited sensitivity of 86% and a specificity 76% for EVDRI (Paper II). Furthermore, the performance of polymerase chain reaction (PCR) of the 16S rRNA gene for the diagnosis of EVDRI was evaluated. This method showed a good concordance to bacterial culture of CSF and the results could be used to direct decisions regarding antimicrobial therapy prior to culture results. Additionally. the results did not indicate that false negative CSF cultures are common in patients treated with an EVD (Paper III). Finally we attempted to characterise the CSF proteome of EVDRI with mass spectrometry. However, no individual proteins were differentially expressed between subjects with and without EVDRI, probably due to large heterogeity of the CSF proteome of neuro-ICU patients, related to their underlying condition.<br/><br/>In summary, this thesis explores different aspects of EVDRI diagnosis and highlights the need for improved diagnostic methods. The results imply that finding sensitive and specific biomarkers related to the host response will be challenging due to the heterogeneity of the CSF proteome, whereas improved microbiological methods could improve EVDRI diagnostics.}},
  author       = {{Widén, Johan}},
  isbn         = {{978-91-8021-639-5}},
  issn         = {{1652-8220}},
  language     = {{swe}},
  number       = {{2024:141}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund university, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{On the diagnosis of external ventricular drain related infections - Incidence, biomarkers and microbiological methods}},
  url          = {{https://lup.lub.lu.se/search/files/198278748/e-spik_ex_Widen.pdf}},
  year         = {{2024}},
}