Available via license: CC BY-NC-ND 4.0
Content may be subject to copyright.
Analysis of the management of ventriculitis cases at a
UK neurosurgery centre
Daniel Lilley
*
, Peter Munthali
Department of Microbiology, University Hospitals Coventry & Warwickshire NHS Trust (UHCW), Clifford Bridge Rd, Coventry CV2
2DX, UK
ARTICLE INFO
Article history:
Received 21 December 2021
Accepted 13 July 2022
Available online 14 August 2022
Key words:
Ventriculitis
Antimicrobial stewardship
Neurosurgery
CSF shunts
External-ventricular drainage
SUMMARY
Background: Ventriculitis is an infection of the ventricular system of the central nervous
system associated with neurosurgery and/or indwelling medical devices mainly caused by
coagulase-negative staphylococci and increasingly by Gram-negative bacilli and other
Gram-positive bacteria. The Infectious Diseases Society of America (IDSA) and the
neurosurgery department University Hospital Coventry and Warwickshire (UHCW) have
treatment guidelines for ventriculitis which recommend antimicrobials and device removal.
Methods: Data on ventriculitis cases, their management and outcomes were collected from
electronic laboratory and hospital records as well as patients’ paper records from 2009 to
2019. Cases included patients with CSF shunts or external ventricular drainage. The man-
agement of the cases was then compared to both Infectious Diseases Society of America
(IDSA) and UHCW guidelines. The data collected included the causative organisms and the
use of inappropriate antimicrobials. The cost of inappropriate antimicrobials was calculated.
Results: 99 patients with microbiologically confirmed ventriculitis were identified. Some
cases had multiple devices and the total number of devices was 105.98% of cases had
medical device removal as part of their care. Only 50% and 56% of cases had antimicrobial
treatment which was compliant with local (UHCW) and IDSA guidelines, respectively. The
most frequently inappropriate antimicrobials used were meropenem and linezolid, at an
estimated cost of £201,172 over 10 years. The most frequently isolated organisms were
coagulase negative staphylococci. Mortality rate was estimated at 14% of cases.
Conclusions: We report the first analysis of the management of ventriculitis cases at
UHCW over a 10-year period and demonstrate the importance of antimicrobial steward-
ship. We also report the local epidemiology of causes of ventriculitis at UHCW which will
guide the empirical treatment of ventriculitis at UHCW.
ª2022 Published by Elsevier Ltd on behalf of The Healthcare Infection Society.
This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Ventriculitis is an infection of the ventricular system of the
central nervous system. Most commonly it occurs as a
complication of neurosurgery, but also after head injury [1,2].
Ventriculitis typically occurs in association with medical
devices, such as external-ventricular drains (EVD) or ven-
triculoperitoneal shunts (VP shunts). EVDs are used for short-
term regulation and monitoring of intracranial pressure, for
the administration of certain medications and the collection of
cerebrospinal fluid (CSF) samples [3]. VP shunts are used for
*Corresponding author.
E-mail address: Dan.lilley@nhs.net (D. Lilley).
Available online at www.sciencedirect.com
Infection Prevention in Practice
journal homepage: www.elsevier.com/locate/ipip
https://doi.org/10.1016/j.infpip.2022.100240
2590-0889/ª2022 Published by Elsevier Ltd on behalf of The Healthcare Infection Society. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Infection Prevention in Practice 4 (2022) 100240
long term regulation of intracranial pressure, particularly in
patients with hydrocephalus. Ventriculitis is difficult to define
as the clinical presentation varies depending on the causative
organism and the clinical scenario. A combination of symp-
toms, laboratory findings, imaging findings and clinical judge-
ment are used to make a diagnosis [4]. The epidemiology of
ventriculitis varies between location and the type of neuro-
logical device used, with some studies demonstrating a 20%
incidence rate [5]. University Hospital Coventry and Warwick-
shire (UHCW) has a busy neurosurgical unit, and is estimated to
carry out over 3000 neurosurgical procedures per year [6].
Currently, the local epidemiology of ventriculitis has not been
investigated previously.
The management of ventriculitis can be lengthy and
expensive and ventriculitis can lead to serious long-term
sequelae and even result in death. [7e9].
Device-associated ventriculitis is complicated by biofilm
formation on the devices with organisms becoming pheno-
typically resistant to antimicrobials while remaining sensitive
in their planktonic form [10,11]. Studies show that coagulase-
negative staphylococci and Staphylococcus aureus are the
most frequent causes of ventriculitis but multi-drug resistant
Gram-negative organisms are increasingly becoming impor-
tant [12e14].
The treatment of ventriculitis at UHCW utilises a multi-
disciplinary team approach as recommended by the Infectious
Disease Society of America (IDSA) and local trust guidelines
[4,15]. Treatment relies on removal of infected device and
broad-spectrum antimicrobials which should be modified
according to culture results. Antimicrobial treatment is gen-
erally given for at least 14 days post CSF sterility taking into
account the clinical response and causative organism.
Inappropriate antimicrobial use promotes antimicrobial
resistance [16], a global threat on a par with climate change
[17]. Good antimicrobial stewardship requires that the anti-
microbial choice is evidence-based [18]. Ventriculitis, as a
healthcare-associated infection is likely to be caused by multi-
drug resistant organisms and thus poses a challenge for treat-
ment [19e21]. Furthermore, the use of broad-spectrum anti-
microbials in these cases causes harm to the patient’s gut
microbiome. [22e25].
We analysed the management of culture proven ventriculitis
cases over a 10-year period from 2009 to 2019. The aim of this
study was twofold. Firstly, to compare the management of
ventriculitis cases at UHCW with IDSA and UHCW treatment
guidelines and to identify areas for improvement in treatment
of ventriculitis at UHCW. Secondly, to document the epidemi-
ology of microbiologically proven ventriculitis in UHCW. This
information will be used to revise the ventriculitis empirical
antimicrobial treatment guidelines at UHCW.
To the best of our knowledge there has been no published
study carried out on the treatment of all microbiologically
proven cases of ventriculitis, although audits of EVD-related
infections have been conducted [26e28].
Methods
Ethical approval for the study was obtained from Warwick
Medical School (BSREC Number- BSREC- CDA- SSC2-2019-33).
To identify microbiologically proven ventriculitis, a search
of the microbiological database at UHCW for the period 2009
to 2019 was conducted according to the criteria in Table I
and further searches were carried out in UHCW’s clinical
result reporting system (CRRS) according to criteria and
methodology in Table I I. CRRS is an electronic patient record
system which captures results of all patient investigations as
well as patient correspondence between healthcare pro-
viders. The paper notes of patients identified as having
microbiologically proven ventriculitis were examined to
determine antimicrobials given and duration of treatment
(Figure 1). There was cross reference between the pre-
scription charts and the time of the ventriculitis episode to
ensure that the treatment given was for ventriculitis. The
first and last day of the antimicrobial administration were
used to calculate the length of the course using Microsoft
Excel (Microsoft office 365). Interruptions to antimicrobial
administration were recorded.
Patients with incomplete notes around the ventriculitis
episode were excluded from the study. Notes were considered
incomplete where older volumes were unable to be sourced for
a variety of reasons such as being at a different hospital site.
An attempt was made to determine the likelihood of con-
tamination of a CSF samples by examination and doc-
umentation of CSF samples being taken aseptically. Where
antimicrobials were administered via the intraventricular (IT)
route, notes were examined for documentation of adherence
to strict infection prevention and control procedures as rec-
ommended by the guidelines.
The duration of treatment was calculated by taking the day
of culture negative CSF to the day antimicrobials were stop-
ped. Mortality from ventriculitis was determined if ventriculitis
was documented as a cause of death in the medical notes.
Death certificates were not examined.
Data analysis
To simplify the data analysis and improve accuracy, a tool
was created which condensed the guidelines to antimicrobial
name, indication, route of administration and treatment
duration (Table III). IDSA guidelines include some
Table I
Search criteria used for initial search to identify probable cases of
ventriculitis
Search criteria Rationale
CSF samples received
within the last 10 years
In order to limit the number of
cases to a manageable number
and to minimise amount of patient
data collected.
Patient’s located to
neurosurgical ward 43
Ward 43 is the neurosurgical
wards at UHCW
Ventriculitis is a highly complex
and specialised condition so
patients should be treated with
facilities equipped for this.
Exclusion of organisms
which cause
acute meningitis e.g.
Neisseria meningitidis,
Streptococcus
pneumoniae
Ventriculitis is an opportunistic
infection occurring as a
complication of neurological
disease or treatment and acute
meningitis organisms are not
considered to be ventriculitis.
D. Lilley, P. Munthali / Infection Prevention in Practice 4 (2022) 1002402
antimicrobials which were not available at UHCW such as
oxacillin, and therefore this table reflects feasible anti-
microbial choice based on the local formulary. Each patient’s
treatment was compared to both UHCW and IDSA guidelines
using this tool. For antimicrobial use that deviated from the
guidelines, the CRRS was reviewed for allergy to anti-
microbials and the antimicrobial sensitivities. Duration of
treatment was calculated by taking the day of culture neg-
ative CSF to the day when the antimicrobials were stopped.
Both sets of guidelines base duration of treatment on the
organism isolated. Initially this is based on the Gram stain
results until a final identification is obtained. The number of
caseswhich met the treatment duration of 14 days for Gram-
positive organisms and 21 days for Gram-negative organisms
(recommended treatment duration during the study period)
was then calculated. Where there was deviation from guide-
lines for antimicrobial choice or course length, the medical
notes were examined for the rationale. Where this was not
evident, it was considered inappropriate in this study.
Meropenem can be used empirically in accordance with the
IDSA guidelines, but empirical linezolid is not recommended.
In order to account for empirical use of meropenem, we cal-
culated the duration of inappropriate treatment from the
date at which cultures grew the causative organism to the
time when meropenem was stopped. The actual treatment
regimen (number of doses/day) was not collected, so it was
estimated that all patients would be given the recommended
three times-a-day (meropenem) or twice-a-day (linezolid).
Finally, costings for each drug based on those detailed in the
online version of British National Formulary [29] and this was
used to calculate the total cost of inappropriate use of mer-
openem and linezolid.
To aid the clarity of results, the organisms were grouped
into genera, Enterobacteriaceae family or miscellaneous
Gram-positive or Gram-negative organisms where there was
only one isolate from a family or genus. These results were then
displayed graphically with full identification to species level
where this was available. Antimicrobial choice was then com-
pared with culture results to determine if its use was in
accordance with guidelines.
Results
There were 99 patients with confirmed ventriculitis and the
treatment administered in these cases was examined. The
exclusion criteria are detailed in Figure 1.
Table II
Criteria and methodology for examination of patient electronic health records on the CRRS system at UHCW
Search criteria Method of searching
Criteria for
ventriculitis
Cases were not considered ventriculitis if there were no indwelling devices used, or electronic
documentation made no reference to ventriculitis or healthcare associated meningitis
Exclusion criteria: Negative culture
Date of first CSF
sample positive
Microbiology section of CRRS was filtered to only include CSF samples. These were then manually searched
for the first sample which had an isolated organism
Date at which CSF
samples become
negative
Of the CSF samples, the subsequent samples were examined to determine when they became negative (i.e.
No growth at 48 hours reported on the CSF microbiology results). Once a negative sample was identified, we
recorded this and continued to examine the remaining CSF samples. To aid in determining the date of
resolution we also collected CSF white cell count (WCC), CSF protein and CSF glucose where these were
available.
Recurrent infection was defined as 28 days from first positive CSF i.e. if the sample became negative during
this time but then became positive again, this was considered a recurrent infection
Organism
Identified
Positive CSF samples had the organism(s) recorded into Microsoft Excel 365ª. Organisms were given a two-
letter key.
Where the comment provided by microbiology suggested the isolate was of questionable significance, it was
considered positive if the criteria they set out in the result comment was met,
or if the medical device was removed,
or if the patient received treatment
for this infection.
Exclusion criteria: Single CSF sample sent, Documentation of organism as insignificant, no intracranial
devices present
Removal of
intracranial
device
The “theatre” tab of CRRS was examined to determine if devices were present and if they were removed.
The date at which this procedure was done was also recorded.
We also recorded what the type of intracranial device was to assist with analysis of antimicrobial selection.
Occasionally there was a lack of documentation for removal of devices. When this was the case, the
following judgements were made:
1. If the patient had an EVD and subsequently had a VP-shunt, this was counted as a removal.
2. If EVD was sent for culture
3. Paper notes were examined to look for written documentation
4. If there was still no definitive evidence of removal, it was assumed to not have been removed.
Mortality Patient records were examined to determine if the patient was deceased. In this case, it was only recorded if
the patient had died whilst receiving treatment for ventriculitis or it was stated on the documentation for
the cause of death.
D. Lilley, P. Munthali / Infection Prevention in Practice 4 (2022) 100240 3
Descriptive statistics for studied population
Of the 99 patient records examined, 43% of the positive
cultures occurred between 2012 and 2014 (Figure 2). EVDs and
VP shunts were associated with most cases (73% and 18%
respectively). The remainder were either other device-related
infections or CSF leaks, which were included due to clinicians
having documented “ventriculitis” or “healthcare-associated
meningitis” during the treatment period (Table IV). Some
patients had multiple devices inserted due to the replacement
of an infected device and subsequent reinfection. In order to
minimise amount of patient identifiable information, the
indication for these devices or any other demographic data
were not recorded.
Comparison of antimicrobial treatment administered
and costing
Of the 105-total number of device-related ventriculitis (CSF
leak was not included), 95% were removed. There were several
cases of ventriculitis which had multiple devices in situ. There
was a large amount of variation in the timeframe for removal
with an average time of 10 days (Standard deviation (SD)
13.95), with a range of -4 dayse67 days (some devices were
removed prior to cultures becoming positive). For anti-
microbial selection, 56% received antimicrobial therapy which
matched the IDSA guidelines and 50% received antimicrobial
therapy which matched the UHCW guidelines. There were large
amounts of variation in the length of treatment, with average
length of antimicrobial treatment of 19 days (SD 17.56)
(Table V), with a range of -6 to 67 days (1 case had a further
positive culture which occurred after antimicrobials were
stopped). IT antimicrobials were given to 55 patients, of which
49% of these had documentation for method of administration
recommended by the guidelines. Fungal isolates were all
treated in accordance with IDSA guidelines for antifungal
agents and these guidelines provide no recommended duration
of treatment regime. UHCW does not provide guidelines on the
management of fungal ventriculitis as such cases are managed
by microbiologists on a case by case basis.
Only eight cases of ventriculitis had a treatment duration
matching the guideline recommendation (Table VI). Approx-
imately half of cases were under the recommended duration
and half exceeded the recommended length.
The most commonly misused antimicrobials not recom-
mended by either IDSA or UHCW guidelines were meropenem
and linezolid (Table VII). Meropenem was used for Gram pos-
itive organisms in 36 cases. Linezolid was inappropriately used
in 9 cases where a coagulase negative staphylococcus was
isolated (Table VIII). The cost of misused meropenem and
linezolid was estimated to be £42,752 and £158,420 respec-
tively, over the 10 years of this study. This equates to
approximately £20,117 per annum spent on inappropriate
antimicrobial use in the management of ventriculitis at UHCW.
Outcome of ventriculitis
The average time for cultures to become negative also
showed significant variation, with an average of 8 days (SD
10.99), with a range of 0e70 days. However, several cases
lacked adequate follow up cultures so this value may not be
representative. CSF WCC, protein, and glucose showed no
correlation to infection resolution and were not used to
determine treatment outcome. Mortality rate was 14% of cases
of confirmed ventriculitis over the 10-year period.
Causative organisms of ventriculitis at UHCW
123 organisms were identified from 99 cases, with multiple
isolates being identified in 19 cases. The clinical significance of
all the isolates was occasionally difficult to ascertain, owing to
Figure 1. Data collection processes showing inclusion and exclusion criteria.
D. Lilley, P. Munthali / Infection Prevention in Practice 4 (2022) 1002404
variable documentation. Aseptic technique was documented in
53% of positive CSF samples. The most common organisms
identified were coagulase-negative staphylococci. Of these, 12
were identified to species level with Staphylococcus epi-
dermidis being the most common (11). Enterobacteriaceae
were the most common Gram-negative organisms identified,
with Klebsiella pneumoniae being the most common species
identified. Candida species were the only fungal causes and
were identified in 6 cases. C. albicans was the most frequently
identified species (Figure 3).
Discussion
IDSA guidelines state that CSF shunt or drain-related ven-
triculitis should be managed by the removal of such devices [4]
combined with targeted antimicrobials. Antimicrobial treat-
ment alone has a low probability of success [30], or high risk of
recurrence [31]. A common feature of device-related infec-
tions is adherence and biofilm formation, which are difficult to
treat with antimicrobials alone due to the immune evasion and
intrinsic tolerance to antimicrobials [32] and therefore, anti-
microbials alone are not recommended for ventriculitis man-
agement. Most cases did have device removal at UCHW but
there was significant variation in when devices were removed.
The reason for this was difficult to ascertain, owing to variation
in documentation. When intracranial devices should be
removed is controversial because there is little consensus on
timing of removal and the risk of recurrence being higher if
devices remain in-situ [30,33]. This suggests several different
approaches for when devices should be removed, and
Table III
Analysis tool which was used to assist in the comparison of antimicrobial choice and duration of treatment
IDSA guidelines
Organism Antimicrobial (a) Antimicrobial (b) Antimicrobial (c) Antimicrobial (d) Duration
Staphylococcus
aureus
Vancomycin*Rifampicin Linezolid 10e14 days
Coagulase negative
Staphylococci
Vancomycin*Rifampicin
Enterococcus faecalis Linezolid
Propionibacterium
(Cutibacterium)
acnes
Penicillin G
Gram negative bacilli In vitro sensitivities ceftriaxone Cefotaxime 10-14/21 days
Pseudomonas spp. Cefepime ceftriaxone Meropenem Aztreonam
ESBL Meropenem
Acinetobacter spp. Meropenem Polymyxin B Colistin
Resistant Gram-
negative bacilli
Meropenem
Candida spp. Amphotericin Fluconazole 5-flucytosine
Antimicrobial (a) is first line, with alternatives (b-d) as options where antimicrobial (a) is not appropriate. In the case of rifampicin,
this is used in combination and not in isolation. *Vancomycin can be given IV with IT being reserved for cases responding poorly to
systemic antimicrobial. These guidelines have been modified to reflect what is available at UCHW based on trust formulary, for
example nafacillin is first line for methicillin sensitive Staphylococcus aureus in the IDSA guidelines but is not available at this
hospital. ESBL ¼Extended spectrum beta-lactamase producers
UHCW guidelines
Device Organism Antimicrobial (a) Antimicrobial (b) Antimicrobial (c) Duration
EVD Coagulase negative
Staphylococci
Vancomycin (IT) Time for device in situ,
sterile CSK before
new EVD/shunt
Staphylococcus
aureus
Flucloxacillin (IV) Vancomycin (IT)
Gram negative bacilli Meropenem (IV) Ceftriaxone (IV Dependent on clinical
response and CSF
Enterococcus spp. Linezolid Dependent on clinical
response and CSF
VP/VA shunt Coagulase negative
Staphylococci
Vancomycin (IV) Rifampicin (oral) Time for device in situ,
sterile CSF before new
EVD/shunt
Staphylococcus
aureus
Flucloxacillin (IV) Vancomycin (IV) Rifampicin (oral)
Gram negative bacilli Meropenem (IV) 14 days
Antimicrobial choice is monotherapy, with a choice between antimicrobial (a) and (b). Exception is rifampicin for S. aureus. related VP
shunt infection
D. Lilley, P. Munthali / Infection Prevention in Practice 4 (2022) 100240 5
documentation for a rationale is lacking. According to UHCW
policy, documentation should be accessible via the “Theatre”
tab of CRRS but for several cases this was either not present or
inferred from other sources.
Meropenem is useful for the treatment of ventriculitis, due
to good CSF penetration and broad spectrum of activity [34].
Empirical meropenem is recommended by the IDSA. Mer-
openem is only recommended for the treatment Gram-
negative organisms and is not for the management of
Staphylococci or Enterococcal infections [35,36]. Although
meropenem is effective for the treatment of Staphylococcus
aureus infections which are methicillin-sensitive, it has little or
no activity against most other staphylococci [37,38]. Fur-
thermore, the continued use of broad-spectrum antimicrobials
when not required is a concern for antimicrobial stewardship.
Treatment with unnecessary or inappropriate antimicrobials
increases the risk of antimicrobial resistance development [39]
and risk of Clostridioides difficile infection [40]. In addition,
the emergence of carbapenem-resistant Enterobacteriaceae
has been declared a significant threat by the CDC [41] and
Public Health England (now UK Health Security Agency) [42].
The rationalisation of antimicrobial therapy is a vital compo-
nent of infection management and documentation was lacking
in many of the cases examined.
This study also demonstrates the potential financial costs of
inappropriate antimicrobial use. For serious and challenging
infections such as ventriculitis, it may be understandable to
continue empirical antimicrobials despite microbiological
evidence. Studies have shown that this is a common, complex
and multi-factorial phenomenon [43,44]. Further investigation
of these factors is outside the scope of this study. Our
recommendations to improve antimicrobial use are education
and feedback of these results to all members of the
multidisciplinary team to promote discussion to identify
interventions to improve the antimicrobial treatment of ven-
triculitis in the future. Such an approach is a cornerstone of
antimicrobial stewardship and there is evidence to support its
effectiveness [45,46]. Further studies are needed to monitor
any improvement in the management of ventriculitis in UHCW.
Figure 2. Number of single positive cultures of ventriculitis per year which is used as a proxy to determine the number of cases of
ventriculitis per year.
Table IV
Clinical background of ventriculitis cases
Clinical background Number of
devices
Percentage of
ventriculitis cases (%)
EVD 76 73
VP shunt 21 20
Post neurological surgery 1 1
CSF leak 3 3
Lumbar drain 3 3
Metal work in-situ 2 2
Graft infection 1 1
Table V
Number of cases of ventriculitis managed in accordance with IDSA
and UCHW guidelines
Treatment recommended Number
receiving
treatment
(%)
Average length
of treatment
was received
(days), with STD
in parentheses.
Medical device removal 99 (94) 10.25 (13.95)
IDSA antimicrobial selection 57 (56) 19 (17.56)
UHCW antimicrobial selection 50 (50)
Average length of treatment with standard deviation in parentheses
was also calculated, with antimicrobial representing the average
length of treatment.
D. Lilley, P. Munthali / Infection Prevention in Practice 4 (2022) 1002406
The comparative rarity of confirmed ventriculitis in UHCW
means that a long period of time is required for enough ven-
triculitis cases to have occurred to reach significance.
The duration of antimicrobial therapy was highly variable in
this study. Although the IDSA guidelines give recommendations
for the optimal treatment duration, these are based on evi-
dence from poor quality cohort studies, observational studies
and expert opinion. Treatment duration should be based on
clinical response and CSF results [47]. However, CSF culture
results are directly affected by the administration of anti-
microbials prior to CSF sample collection [48] and the CSF WCC
can vary significantly [49]. Therefore, due to variations in
documentation and poor reliability of using CSF parameters to
predict resolution of infection it is difficult to determine the
optimum antimicrobial treatment duration. There was poor
documentation for the rationale of treatment duration used or
why treatment was stopped. The mortality rate seen in this
study is representative of rates from other studies [50e52].
Poor documentation affected every aspect of our data col-
lection. Where treatment deviated from guidelines, there was
a lack of explanation in documented in paper notes. Poor
documentation of aseptic technique of CSF sampling and
method of IT antimicrobial administration may have affected
the results of this study. Although we are confident our results
reflect the reality of treatment of ventriculitis, poor doc-
umentation adds a degree of uncertainty. Often, an indication
for antimicrobials was not documented and was identified by
methods described. What is more, where multiple isolates
were identified it was unclear which were considered sig-
nificant. Furthermore, was difficult to ascertain the decision
making which led to deviation from both sets of guidelines due
to the retrospective nature of this work and variable thor-
oughness of documentation. Inadequate documentation for
medication changes has been shown by studies in different
clinical areas [53,54]. Further research is needed to determine
the root cause for the absence of detailed documentation.
However, restraint should be exercised before simply recom-
mending more documentation as this alone is unlikely to lead
to significant change in patient outcomes because it reduces
time for direct patient care [55,56]. Currently, there is a multi-
disciplinary approach to the management of ventriculitis, with
microbiologist advice but with ultimate clinical responsibility
with the neurosurgical team.
The results of isolated organisms are reflected in other
studies with staphylococci being the most frequent [12,49,57].
Enterococci were the second most common isolate, which is
unusual compared to other studies [12,58]. Enterococcal CSF
infections are often polymicrobial [59]. It is possible that the
empirical use of vancomycin may have selected a single
enterococcal strain and several vancomycin-resistant enter-
ococci isolates were reported. The recent trend in some cen-
tres of increased Gram-negative isolates, especially
Acinetobacter baumannii was not observed in this neuro-
surgical centre [60,61]. The clinical significance of some of the
organisms grown in this study is not clear. Although isolates
were excluded if documented as not clinically significant, the
retrospective nature of this study means it is likely some
organisms included were not clinically significant.
This study has several limitations. The initial search may
have excluded some cases. Although ventriculitis should be
treated on the neurosurgical ward at UHCW, it is possible some
cases may have been treated elsewhere. So-called outliers
(patients who are receiving specialist medical or surgical care
in locations other than their specialist ward) are frequent, with
one study reporting just under 10% of patients receive care as
outliers [62]. Many patients in this study receiving some care on
ICU, so it is possible cases would have been missed if ven-
triculitis occurred whilst on ICU and the patient died before ICU
discharge. It is also possible that excluding CSF samples with
organisms classically causing acute meningitis, may have
Table VII
Estimate of costing of the inappropriate use of meropenem and
linezolid during 2009e2019
Antimicrobial Total duration
of inappropriate
use (days)
Estimated
inappropriate
doses
Cost (£)
Meropenem 835 2505 42,752.34
Linezolid 178 356 158,420
Table VI
Number of cases of ventriculitis which matched treatment length
recommended by the guidelines
Duration of treatment Number of bacterial
infections treated
Gram-positive bacteria
Treatment length less than
recommendation by guidelines
29
Recommended treatment duration 8
Treatment length greater than
recommendation by guidelines
37
Gram-negative bacteria
Treatment length less than
recommendation by guidelines
10
Recommended treatment duration 0
Treatment length greater than
recommendation by guidelines
10
For Gram-positive infections, the recommended duration of treatment
is 10e14 days. For Gram-negative infections, the recommended
treatment duration is 10e14 days, some experts suggest treatment for
21 days, [4].
Table VIII
Number of cases where antimicrobial choice was inappropriate
with rationale as to why this was considered inappropriate
Antimicrobial Number
of
cases
used
Number of
cases with
inappropriate
use
Rationale for
inappropriate use
Meropenem 41 36 Use for Gram-positive
organism
Linezolid 22 9 Use in coagulase-
negative staphylococci
Vancomycin IV 36 1 Use for Gram-negative
organism
Vancomycin IT 46 1 Use for Gram-negative
organism
D. Lilley, P. Munthali / Infection Prevention in Practice 4 (2022) 100240 7
excluded cases of ventriculitis. There are several case reports
of ventriculitis caused by such organisms [63,64]. The rarity of
such cases is unlikely to have a significant impact on the quality
of our findings.
Another potential limitation is the clustering of cases
between 2012 and 2014. As the both the IDSA and UHCW
guidelines were published in 2017, the evidence guiding the
management prior to this may have differed in recom-
mendations. However, many studies published pre-2017 show
similar treatment recommendations [5,35,65]. The costing
data may also have been affected by this clustering of cases.
We used an estimate for treatment regimes in this study and
used current pricing for meropenem and linezolid used in
cases treated over 10 years. As medication prices vary over
time [66], this value is an estimate only and the true figure will
differ. In addition to this, dosing was assumed to be that of
normal renal function and no data was collected about
patient’s renal function. Therefore, this would also over-
estimate cost if patients had reduced frequency or dose of
antimicrobial depending on their renal function [29]. Fur-
thermore, this study only analysed cases at one centre and
therefore how relatable these findings are to other sites is
difficult to comment on. However, inappropriate antimicrobial
use is well-recognised in healthcare.
To the best of our knowledge there are no other published
studies on the local management of all cases of confirmed
ventriculitis. In addition, the data presented here further sup-
ports the importance of antimicrobial stewardship. The data on
the causative organisms identified in the study may help sup-
port future empirical management of ventriculitis at UHCW.
We suggest that further studies should be conducted about
the management of suspected or culture-negative ven-
triculitis. In addition, research into the root cause of poor
documentation observed in this study should be conducted.
Future research may also investigate the possible causes for
the current trend in decline in cases. One potential cause of
this may be improved neurosurgical technique, which several
studies have shown to reduce incidence of ventriculitis
[67,68].
Conclusions
This study provides detailed analysis of the management of
confirmed ventriculitis cases at UHCW including the pattern of
causative organisms. The study highlighted the importance of
antimicrobial stewardship and the potential financial implica-
tions of inappropriate antimicrobial use.
Acknowledgments
I would like to thank my project supervisor for all their
support and guidance offered throughout the course of this
study. I would also like to thank the administrative staff in the
pathology department for their help with requesting patient
notes and the Microbiology IT department for performing the
initial search. Finally, I would like to thank my partner for all
her support.
Author statement
Dr Peter Munthali conceptualised the project, supervised
and edited the manuscript
Dr Daniel Lilley undertook the research, analysis and writing
of the manuscript
Figure 3. Identification of micro-organisms isolated from CSF samples of ventriculitis cases. Full names of identified organisms are as
follows: VRE¼Vancomycin Resistant enterococci, Citrobacter koseri, Klebsiella oxytoca, Proteus miirabilis, Escherichia.
D. Lilley, P. Munthali / Infection Prevention in Practice 4 (2022) 1002408
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial or not-for-profit sectors.
Declaration of interest
No competing interests are present from the authors of this
work.
References
[1] Kourbeti IS, Vakis AF, Ziakas P, Karabetsos D, Potolidis E,
Christou S, et al. Infections in patients undergoing craniotomy:
risk factors associated with post-craniotomy meningitis.
J Neurosurg 2015;122:1113e9.
[2] Lin C, Zhao X, Sun H. Analysis on the risk factors of intracranial
infection secondary to traumatic brain injury. Chin J Traumatol
2015;18:81e3.
[3] Lozier AP, Sciacca RR, Romagnoli MF, Connolly Jr ES. Ven-
triculostomy-related infections: a critical review of the liter-
ature. Neurosurgery 2002;51:170e81; discussion 81-2.
[4] Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan S, Scheld M,
et al. 2017 Infectious Diseases Society of America’s Clinical
Practice Guidelines for Healthcare-Associated Ventriculitis and
Meningitis. Clin Infect Dis 2017;64:e34.
[5] Humphreys H. Jenks PJ Surveillance and management of ven-
triculitis following neurosurgery. J Hosp Infect 2015;89:281e6.
[6] University Hospitals Coventry & Warwickshire. https://www.
uhcw.nhs.uk/our-services-and-people/our-departments/
neurosciences/. Date accessed:20/01/2021.
[7] Phan K, Schultz K, Huang C, Halcrow S, Fuller J, McDowell D,
et al. External ventricular drain infections at the Canberra Hos-
pital: A retrospective study. J Clin Neurosci 2016;32:95e8.
[8] Patwardhan RV. Nanda A Implanted ventricular shunts in the
United States: the billion-dollar-a-year cost of hydrocephalus
treatment. Neurosurgery 2005;56:139e45.
[9] Hariri O, Farr S, Lawandy S, Zampella B, Miulli D. Siddiqi J Will
clinical parameters reliably predict external ventricular drain-
associated ventriculitis: Is frequent routine cerebrospinal fluid
surveillance necessary? Surg Neurol Int 2017;8:137.
[10] Pandey S, Li L, Deng XY, Cui DM, Gao L. Outcome Following the
Treatment of Ventriculitis Caused by Multi/Extensive Drug
Resistance Gram Negative Bacilli; Acinetobacter baumannii and
Klebsiella pneumonia. Front Neurol 2019;9:1174.
[11] Portillo ME, Corvec S, Borens O. Trampuz A Propionibacterium
acnes: an underestimated pathogen in implant-associated infec-
tions. BioMed Res Int 2013;2013:804391.
[12] Srihawan C, Habib O, Salazar L. Hasbun R Healthcare-Associated
Meningitis or Ventriculitis in Older Adults. J Am Geriatr Soc 2017;
65:2646e50.
[13] Cicek-Senturk G, Ozay R, Kul G, Altay F, Kuzi S, Gurbuz Y, et al.
Evaluation of Postoperative Meningitis: Comparison of Meningitis
Caused by Acinetobacter spp. and Other Meningitis. Turk Neu-
rosurg 2018.
[14] Shang F, Xu Y, Wang N, Cheng W, Chen W, Duan W. Diagnosis and
treatment of severe neurosurgical patients with pyogenic ven-
triculitis caused by gram-negative bacteria. Neurol Sci 2018;
39:79e84.
[15] Munthali P, Li M. Neurosurgical antimicrobial guidelines 3edn.
Microbiology, University Hopsital Coventry and Warwickshire.
Clifford Bridge Rd, Coventry, CV2 2017;2DX:6e8.
[16] Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M.
A systematic review and meta-analysis of the effects of anti-
microbial consumption on antimicrobial resistance. BMC Infect
Dis 2014;14:13.
[17] Davies SC. Annual report of the chief medical office. Infections
and rise of antimicrobial resistance, ume Two. London: Depart-
ment of Health; 2013. 2011.
[18] Dyar OJ, Huttner B, Schouten J, Pulcini C. What is antimicrobial
stewardship? Clin Microbiol Infect 2017;23:793e8.
[19] Sahu MK, Siddharth B, Choudhury A, Vishnubhatla S, Singh S,
Menon R, et al. Incidence, microbiological profile of nosocomial
infections, and their antimicrobial resistance patterns in a high
volume Cardiac Surgical Intensive Care Unit. Ann Card Anaesth
2016;19:281e7.
[20] Zhu X, Tong A, Wang D, Sun H, Chen L. Dong M Antimicrobial
resistance patterns of Gram-negative and Gram-positive strains
isolated from inpatients with nosocomial infections in a tertiary
hospital in Beijing, China from 2011 to 2014. J Chemother 2017;
29:317e20.
[21] Blomberg B, Mwakagile DS, Urassa WK, Maselle SY, Mashurano M,
Digranes A, et al. Surveillance of antimicrobial resistance at a
tertiary hospital in Tanzania. BMC Publ Health 2004;4:45.
[22] Zhang L, Huang Y, Zhou Y, Buckley T. Wang HH Antimicrobial
administration routes significantly influence the levels of anti-
microbial resistance in gut microbiota. Antimicrob Agents Che-
mother 2013;57:3659e66.
[23] Isaac S, Scher JU, Djukovic A, Jimenez N, Littman D, Abramson S,
et al. Short- and long-term effects of oral vancomycin on the
human intestinal microbiota. J Antimicrob Chemother 2017;
72:128e36.
[24] Theriot CM. Young VB Interactions Between the Gastrointestinal
Microbiome and Clostridium difficile. Annu Rev Microbiol 2015;
69:445e61.
[25] Martinez JL. General principles of antimicrobial resistance in
bacteria. Drug Discov Today Technol 2014;11:33e9.
[26] Lwin S, Low SW, Choy DK, Yeo TT. Chou N External ventricular
drain infections: successful implementation of strategies to
reduce infection rate. Singap Med J 2012;53:255e9.
[27] Sam JE, Lim CL, Sharda P, Wahab NA. The Organisms and Factors
Affecting Outcomes of External Ventricular Drainage Catheter-
Related Ventriculitis: A Penang Experience. Asian journal of
neurosurgery 2018;13:250e7.
[28] Albano S, Berman B, Fischberg G, Siddiqi J, Bolin Y, Khan Y, et al.
Retrospective Analysis of Ventriculitis in External Ventricular
Drains. Neurology research international 2018;2018:5179356.
[29] Committee JF. British National Formulary (online, accessed 16/
2/2020) London: BMJ Group and Pharmaceutical Press, http://
www.medicinescomplete.com.
[30] Schreffler RT, Schreffler AJ, Wittler RR. Treatment of cere-
brospinal fluid shunt infections: a decision analysis. Pediatr Infect
Dis J 2002;21:632e6.
[31] James HE, Walsh JW, Wilson HD, Connor JD. The management of
cerebrospinal fluid shunt infections: a clinical experience. Acta
Neurochir 1981;59:157e66.
[32] Bryers JD Medical biofilms. Biotechnol Bioeng 2008;100:1e18.
[33] Kestle JR, Garton HJ, Whitehead WE, Drake JM, Kulkarni AV,
Cochrane DD, et al. Management of shunt infections: a multi-
center pilot study. J Neurosurg 2006;105:177e81.
[34] van de Beek D, Drake JM, Tunkel AR. Nosocomial bacterial
meningitis. N Engl J Med 2010;362:146e54.
[35] Brown JdLRBPDLIKPEM The management of neurosurgical
patients with postoperative bacterial or aseptic meningitis or
external ventricular drain-associated ventriculitis. Br J Neurosurg
2000;14:7e12.
[36] Lich BF, Conner AK, Burks JD, Glenn CA, Sughrue ME. Intrathecal/
Intraventricular Linezolid in Multidrug-Resistant Enterococcus
faecalis Ventriculitis. J Neurol Surg Rep Germany 2016:e160e1.
[37] White RL, Friedrich LV, Manduru M, Mihm LB. Bosso JA Com-
parative in vitro pharmacodynamics of imipenem and meropenem
against ATCC strains of Escherichia coli, Staphylococcus aureus
and Bacteroides fragilis. Diagn Microbiol Infect Dis 2001;
39:39e47.
D. Lilley, P. Munthali / Infection Prevention in Practice 4 (2022) 100240 9
[38] Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ,
et al. Comparative review of the carbapenems. Drugs 2007;
67:1027e52.
[39] Baur D, Gladstone BP, Burkert F, Carrara E, Foschi F, Dobele S,
et al. Effect of antimicrobial stewardship on the incidence of
infection and colonisation with antimicrobial-resistant bacteria
and Clostridium difficile infection: a systematic review and meta-
analysis. Lancet Infect Dis 2017;17:990e1001.
[40] Hensgens MP, Goorhuis A, Dekkers OM. Kuijper EJ Time interval of
increased risk for Clostridium difficile infection after exposure to
antimicrobials. J Antimicrob Chemother 2012;67:742e8.
[41] Centers for Disease Control and P. Antimicrobial Resistance
Threats in the United States, 2013. Methicillin-Resistant Staph-
ylococcus aureus (MRSA). 2013. Retrieved July 25, 2015.
[42] Crosford P, Keogh B. Re: Addressing the infection risk from
carbapenemase-producing Enterobacteriaceae and other
carbapenem-resistant organisms. In: England PH, editor. Well-
ington house, 133-155 waterloo road; 2014. London SE1 8UG.
[43] Skodvin B, Aase K, Brekken AL, Charani E, Lindemann PC. Smith I
Addressing the key communication barriers between micro-
biology laboratories and clinical units: a qualitative study.
J Antimicrob Chemother 2017;72:2666e72.
[44] Sedrak A, Anpalahan M, Luetsch K. Enablers and barriers to the
use of antimicrobial guidelines in the assessment and treatment
of community-acquired pneumonia-A qualitative study of clini-
cians’ perspectives. Int J Clin Pract 2017;71.
[45] Srinivasan A Antimicrobial stewardship. Why we must, how we
can. Cleve Clin J Med 2017;84:673e9.
[46] Davey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E,
et al. Interventions to improve antimicrobial prescribing
practices for hospital inpatients. Cochrane Database Syst Rev
2017.
[47] Alnimr AA. Protocol for Diagnosis and Management of Cere-
brospinal Shunt Infections and other Infectious Conditions in
Neurosurgical Practice. BCN 2012;3:61e70.
[48] Nigrovic LE, Malley R, Macias CG, Kanegaye JT, Moro-
Sutherland DM, Schremmer RD, et al. Effect of antimicrobial
pretreatment on cerebrospinal fluid profiles of children with
bacterial meningitis. Pediatrics 2008;122:726e30.
[49] 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;47:73e82.
[50] Bari ME, Haider G, Malik K, Waqas M, Mahmood SF. Siddiqui M
Outcomes of post-neurosurgical ventriculostomy-associated
infections. Surg Neurol Int 2017;8:124.
[51] Kumar R, Singhi P, Dekate P, Singh M, Singhi S. Meningitis related
ventriculitis–experience from a tertiary care centre in northern
India. Indian J Pediatr 2015;82:315e20.
[52] Busl KM Healthcare-Associated Infections in the Neurocritical
Care Unit. Curr Neurol Neurosci Rep 2019;19:76.
[53] Peusschers E, Twine J, Wheeler A, Moudgil V, Patterson S. Doc-
umentation of medication changes in inpatient clinical notes: an
audit to support quality improvement. Australas Psychiatr 2015;
23:142e6.
[54] Nelson E, Falls Reynolds P Inpatient. Improving assessment,
documentation, and management. BMJ Qual Improv Rep 2015;4.
[55] Joukes E, Abu-Hanna A, Cornet R, de Keizer. NF Time Spent on
Dedicated Patient Care and Documentation Tasks Before and
After the Introduction of a Structured and Standardized Elec-
tronic Health Record. Appl Clin Inf 2018;9:46e53.
[56] Baumann LA, Baker J, Elshaug AG. The impact of electronic
health record systems on clinical documentation times: A sys-
tematic review. Health Pol 2018;122:827e36.
[57] Weisfelt M, van de Beek D, Spanjaard L, de Gans J. Nosocomial
bacterial meningitis in adults: a prospective series of 50 cases.
J Hosp Infect 2007;66:71e8.
[58] Pintado V, Cabellos C, Moreno S, Meseguer MA, Ayats J,
Meningitis Viladrich PF Enterococcal. A Clinical Study of 39 Cases
and Review of the Literature. Medicine 2003;82.
[59] Chang WN, Lu CH, Huang CR, Chuang YC. Mixed infection in adult
bacterial meningitis. Infection 2000;28:8e12.
[60] Chen F, Deng X, Wang Z, Wang L, Wang K, Gao L. Treatment of
severe ventriculitis caused by extensively drug-resistant Acine-
tobacter baumannii by intraventricular lavage and administration
of colistin. Infect Drug Resist 2019;12:241e7.
[61] Senturk GC, Ozay R, Kul G, Altay FA, Kuzi S, Gurbuz Y, et al.
Evaluation of post-operative meningitis: comparison of meningitis
caused by Acinetobacter spp. and other possible causes. Turk
Neurosurg 2019;29(6):804e10.
[62] Stylianou N, Fackrell R, Vasilakis C. Are medical outliers asso-
ciated with worse patient outcomes? A retrospective study within
a regional NHS hospital using routine data. BMJ Open 2017;
7:e015676.
[63] van den Heuvel N, O’Leary C. Gwee A Meningococcal Meningitis
Complicated by Ventriculitis in an Infant. J Paediatr Child Health
2018;54:213e4.
[64] Ben Shimol S, Einhorn M, Greenberg D. Listeria meningitis and
ventriculitis in an immunocompetent child: case report and lit-
erature review. Infection 2012;40:207e11.
[65] Beer R, Lackner P, Pfausler B. Schmutzhard E Nosocomial ven-
triculitis and meningitis in neurocritical care patients. J Neurol
2008;255:1617e24.
[66] Alpern JD, Zhang L, Stauffer WM. Kesselheim AS Trends in Pricing
and Generic Competition Within the Oral Antimicrobial Drug
Market in the United States. Clin Infect Dis 2017;65:1848e52.
[67] Kulkarni AV, Drake JM, Lamberti-Pasculli M. Cerebrospinal fluid
shunt infection: a prospective study of risk factors. J Neurosurg
2001;94:195e201.
[68] Tulipan N. Cleves MA Effect of an intraoperative double-gloving
strategy on the incidence of cerebrospinal fluid shunt infection.
J Neurosurg Pediatr 2006;104:5e8.
D. Lilley, P. Munthali / Infection Prevention in Practice 4 (2022) 10024010
