Reflective Journal Reading
Reflective Journal Reading
Reflective Journal Reading
ABSTRACT
Acute meningitis remains a devastating disease. Clinicians need a low threshold for suspecting
meningitis, to undertake appropriate investigations and provide treatment in a timely manner, to
minimise the risk of poor outcome in bacterial disease, while limiting unnecessary treatment in viral
meningitis.
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Key points
Viral meningitis is the most common form of meningitis in the UK, but bacterial meningitis continues to
be important, with a high mortality
Clinical features are poor discriminators for meningitis, so urgent investigations, starting with lumbar
puncture, are key
Most patients do not need brain imaging before lumbar puncture. Patients exhibiting clinical features of
brain shift warrant urgent CT. Otherwise, imaging can cause delays in commencing antibiotics, which can
lead to increased mortality
Aim to take 10 mL of CSF during LP. Larger volumes are especially useful to diagnose tuberculous
meningitis, and enable additional aliquots to be available for further diagnostic testing
Prompt testing of CSF and blood by PCR can hasten pathogen diagnosis and improve patient
management
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Definitions
Meningitis is inflammation of the meninges covering the brain. It is a pathological definition. The
cerebrospinal fluid (CSF) typically exhibits an elevated number of leucocytes (or a pleocytosis). In adults,
>5 leucocytes/μL is defined as elevated. Bacterial or viral meningitis is confirmed by the detection of a
pathogen in the CSF. Bacterial meningitis may also be suggested by symptoms of meningism and
appropriate bacteria in the blood.1
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Causes
The most common causes of meningitis in immunocompetent adults in the UK are viruses and bacteria.
Viruses account for up to half of cases. Enterovirus is the commonest, with herpes simplex and varicella
zoster the next most frequent. Streptococcus pneumoniae and Neisseria meningitidis are the
commonest bacteria, together accounting for approximately one-quarter of cases.
Other causes such as Haemophilus influenzae, Listeria monocytogenes, Mycobacterium tuberculosis and
fungi (typically cryptococci) are less frequently detected, together representing <10% of cases.
Currently, many adults with meningitis have no pathogen detected.2–5
Although this article refers to Listeria and tuberculous meningitis, it purposely focuses on the more
common causes, ie viral and bacterial meningitis.
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Clinical features
Clinical features alone cannot confirm the diagnosis of meningitis. A lumber puncture (LP) is essential to
confirm the diagnosis of meningitis and establish the cause.
In one study, 95% of bacterial meningitis patients had at least two symptoms of headache, neck
stiffness, fever and altered consciousness. The latter three features were present together in only 44%
of cases. Neurological deficits are found in around one-third of patients.6 Similar findings are reported
by other studies.7–9
A rash in suspected meningitis makes N meningitidis more likely. However, 37% of meningococcal
meningitis patients have no rash.8 Varicella and enterovirus can also be associated with a rash.
Risk factors for Listeria meningitis include overt or relative immune compromise, the latter including
chronic illness, diabetes, alcohol dependency, malignancy or old age. Listeria meningitis is rarely seen in
immunocompetent adults under 60 years of age.1,10
Travel history, symptoms of otitis media / sinusitis, contact with another person with meningitis, sepsis
or tuberculosis are other useful diagnostic clues.
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Investigations
Lumbar puncture
Lumbar puncture is the key investigation. It enables rapid confirmation of meningitis and type of
infecting organism. Diagnostic yield of LP can be diminished by collecting small CSF volumes. At least 10
mL can be safely removed.11,12
Cerebrospinal fluid remains one of the most rapidly informative tests. Pleocytosis indicates meningeal
inflammation, of which infection is the most common cause. Van de Beek and colleagues reported that
>90% of adults with bacterial meningitis had a CSF leukocyte count >100 cells/μL.6 Absence of
pleocytosis makes meningitis much less likely, but does not completely rule it out. Approximately 1–2%
of patients with bacterial meningitis will have a normal CSF leukocyte count. Positive pathogen
detection and an absence of pleocytosis more frequently occurs among children, the
immunocompromised, those pretreated with antibiotics or with mycobacteria tuberculosis infection.13
Cerebrospinal fluid leukocyte differential can help predict which type of pathogen is causing infection.
Lymphocyte predominance suggests viral, while neutrophil predominance suggests bacterial infection.
There are several exceptions to this general guide, including CSF neutrophil predominance observed in
association with tuberculous meningitis (Table (Table11).
Table 1.
Opening presssure (cm CSF) 12–20 Raised Normal / mildly raised Raised Raised
Appearance Clear Purulent, turbid, cloudy Clear Clear or cloudy Clear or cloudy
CSF WBC (cells/μL) <5 Raised (>100) b Raised (5–1000) b Raised (5–100) b Raised
(5–100) b
CSF plasma glucose ratio >0.66 Very low Normal / slightly low Very low Low
CSF glucose (mmol) 2.6–4.5 Very low Normal / slightly low Very low Low
Cerebrospinal fluid glucose is normally approximately two-thirds the blood (plasma) concentration. It is
often lower in bacterial and tuberculous meningitis. As CSF glucose is influenced by the plasma glucose,
it is essential to measure blood glucose at LP, to obtain an accurate CSF:blood glucose ratio. A CSF:blood
glucose ratio <0.36 is an accurate (93%) marker for distinguishing bacterial from viral meningitis.1
Cerebrospinal fluid protein is normally <0.4 g/L. Elevated protein suggests inflammation. A CSF protein <
0.6 g/L largely rules out bacterial infection.1
Cerebrospinal fluid parameters have been combined into tools to help diagnose bacterial meningitis.
One prediction rule accurately distinguished bacterial from viral meningitis in two adult patient
populations using retrospective data (area under the curve 0.97).14,15 Clinical prediction tools (using
CSF, laboratory and clinical parameters) have also exhibited high accuracy when tested retrospectively
in large child populations.16 No tools have been validated prospectively in adults in the UK.
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Pathogen detection
Cerebrospinal fluid microscopy with Gram stain (or an acid fast stain for M tuberculosis) can rapidly
detect bacteria. It has a sensitivity between 50% and 99%.6 Detection, particularly for M tuberculosis, is
enhanced by collection of >10 mL of CSF and subsequent cytospin.11
Cerebrospinal fluid culture is historically regarded as the ‘gold standard’ for the diagnosis of bacterial
meningitis. It is diagnostic in 70–85% of cases prior to antibiotic exposure. Sensitivity decreases by 20%
following antibiotic pretreatment. Cerebrospinal fluid sterilization can occur within 2–4 hours of
antibiotic administration for meningococci and pneumococci respectively.15 Lumbar puncture should be
performed as soon as possible to maximise pathogen detection.
Blood tests
Blood cultures should always be taken on admission and are helpful when antibiotics are started before
LP. Blood cultures are positive in 50–80% of bacterial meningitis cases.15
Blood PCR is increasingly important, especially as PCR detects bacteria several days after antibiotic
initiation.17 Blood PCR substantially increases the confirmation in meningococcal disease.18
Despite these tests, many patients will not have a cause identified for their meningitis.
Blood biomarkers, such as procalcitonin and C-reactive protein, can help distinguish bacterial from viral
meningitis in adults and can be used to help guide treatment if no aetiology is found.19,20 Host
biomarkers for detecting bacterial meningitis are being actively investigated by our Liverpool group and
others. To date, there is insufficient evidence to recommend their routine use in the NHS.1
Swabs
Throat, nasopharyngeal, and stool swabs are useful for detecting enteroviruses if the CSF PCR is
negative.
Brain imaging
Brain imaging is neither obligatory in the management of meningitis, nor a prerequisite to LP.
Performing neuroimaging before LP is associated with delays in commencing antibiotics, which in turn
can lead to an increase in mortality.12,21 An urgent CT scan should be performed if there are clinical
signs of brain shift. Clinical features indicative of a brain shift include focal neurological signs and
reduced Glasgow Coma Score (GCS) (Box (Box1).1). The 2016 UK meningitis guidelines recommend an LP
be performed without prior neuroimaging if the GCS is >12.1 Patients with a GCS ≤12 should be
considered for critical care, intubation assessment and neuroimaging. Imaging, particularly when
contrast is used, may exhibit meningeal enhancement in meningitis. When brain shift is identified liaison
with critical care and neurosurgical teams are essential.
Box 1.
Indications for brain imaging before lumbar puncture (LP) in suspected meningitisa
Presence of papilloedemab
aTo exclude significant brain swelling or shift that may predispose to cerebral herniation post LP.
bInability to view the fundus is not a contraindication to LP, especially in patients who have had a short
duration of symptoms.
cLumbar puncture without prior neuroimaging may be safe at levels below this.GCS = Glasgow Coma
Score
Treatment
If a patient exhibits signs of airway, breathing or circulatory difficulties (eg in coexisting sepsis),
management should initially focus on stabilisation of these systems.
All patients should be reviewed by a senior clinician. The Royal College of Physicians recommends
consultant review for all acute medical patients within 14 hours of admission. Urgency of review should
be assessed using the National Early Warning Score. The GCS should be recorded for its prognostic
value, and to enable changes to be monitored. Presence of a rash and use of preadmission antibiotics
should also be recorded.
If the patient presents with sepsis, they should be managed according to the sepsis guidelines.22 If the
infective focus of sepsis is meningitis, then the antibiotic treatment should follow the guidelines for
meningitis.1 For example, piperacillin/tazobactam is not recommended for use in sepsis secondary to
meningitis, because of its poor penetration of the blood brain barrier. A recent large open-label trial
showed no benefit of prehospital antibiotics in sepsis.23 Previous trials for meningitis have also been
inconclusive.1 Consequently, the benefit of prehospital antibiotics for suspected meningitis is unclear.
Management of other aspects of sepsis, eg circulation, should follow the sepsis guidelines.22
Treatment for bacterial meningitis is antibiotics, with or without steroids. The choice of antibiotics is a
three stage process: an initial empirical decision based on clinical suspicion, review following microscopy
results, and review again when culture or PCR results are available.
In suspected bacterial meningitis, dexamethasone should be started either shortly before or
simultaneously with antibiotics at 10 mg intravenously (IV) 6-hourly. Up until 12 hours after antibiotic
initiation, dexamethasone can still be started, but the impact of this on mortality has not been studied.
If pneumococcal meningitis is probable, dexamethasone should continue for 4 days. In suspected
tuberculous meningitis, dexamethasone provision should follow the recommended guidelines.11 Once
another cause of meningitis is probable, dexamethasone should be stopped.
There is no specific treatment for viral meningitis. Treatment with aciclovir has only been of proven
benefit in herpes encephalitis, not meningitis. Only if the patient has encephalitic features, such as
impairment of consciousness, focal neurological signs, inflammation of brain parenchyma in the region
of the temporal lobe on cranial imaging, should aciclovir be considered.
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Prognosis
Mortality occurs almost exclusively in bacterial meningitis. Up to 57% in meningococcal sepsis, 30% of
pneumococcal and 7% of meningococcal meningitis without sepsis cases die.1,6
Morbidity is common in bacterial meningitis. Van De Beek's study reported focal neurological deficits in
50% of cases, the commonest being hearing impairment (14%), and 14% of cases exhibited moderate to
severe disability at discharge.6
Few studies have examined outcome in viral meningitis. One recent study, reported one-third of adult
varicella meningitis patients (3/9) suffered sequelae.24 In our experience, viral meningitis patients can
suffer cognitive and psychological sequelae. Headaches occur in one-third of patients. Where there is
concern, patients should access neuropsychological services, which can help detect subtle impairments
and may facilitate functional recovery. Organisations such as the Meningitis Research Foundation
(www.meningitis.org) or Meningitis Now (www.meningitisnow.org), can also provide helpful patient
information and advocacy.
Conclusion
Many meningitis patients in the UK who have a CSF pleocytosis never have a pathogen identified.
Clinicians need to remain vigilant and treat suspected bacterial meningitis promptly. However, with
viruses being the most common cause of meningitis, rapid diagnosis via PCR can limit unnecessary
antibiotic treatment and expedite hospital discharge.
Reflective Journal Reading
Meningitis is an inflammation of the meninges of the brain, which is caused by various pathogens.
Critical care nurses are the first-line clinicians to observe these patients in the ICU, thus, they're an
integral part of the prevention of major complications. Therefore, revisit the anatomy, epidemiology,
and types of meningitis, as well as prevention, nursing care, and treatment for the disease.
Paragraph 2: What do you like about the Article, Journal Paper, or Research?
I liked in this article that it explained further about the disease meningitis which is inflamation of the
brain , and also I liked the nursing management that they did which was , Initial nursing assessment that
includes a thorough history, neurological exam, review of systems, and vital signs. The nursing
assessment must also focus on history of travel, previous infections, medications, and sources of
immunosuppression. The neurological exam consists of cranial nerve assessment, level of consciousness,
motor strength, sensory exam and evaluation of headache. Other signs of meningeal irritation may
include positive Kernig's sign, which is pain and hamstring resistance that is elicited upon passive knee
extension while patient is supine.9 Brudzinski's sign is positive if there's an involuntary flexion of hips
due to passive neck flexion while patient is supine.9(See Testing for meningeal irritation.) Findings from
a neurological exam may include altered mental status, confusion and irritability, vision disturbances
such as photophobia, cranial nerve deficits, and changes in level of consciousness.
The gastrointestinal system may be affected if the patient presents with nausea and vomiting that can
typically be related to meningeal irritation. All other major body systems may be normal depending on
the severity of the initial infection.
Also I liked the Bacterial treatment: Empiric intravenous antibiotics must be given for the specific
organism endemic to the region. When specific organisms are isolated, the appropriate antibiotic may
then be started intravenously. Initial empiric antibiotics include third generation cephalosporins such as
ceftriaxone (Rocephin), or fluoroquinolones such as ciprofloxacin (Cipro).According to researchers, the
use of glucocorticoids, such as dexamethasone (Decadron), with the initiation of the first antibiotic dose
has been shown to decrease unfavorable outcomes and mortality from bacterial meningitis with adults.
However, there's limited data on dexamethasone use in adults, and if given should be initiated with the
first dose of antibiotics for a limited number of days. Steroid use is controversial, and research is
ongoing. In a systemic review, experts suggest, “…routine steroid therapy with the first dose of
antibiotics is justified in most adult patients in whom acute community acquired bacterial meningitis is
suspected.”The major effect of dexamethasone is a decrease in the inflammatory response.
Paragraph 3: What do you dislike about the Article, Journal , or Research?
I actually didn’t like that there was not a world statictics and there wasn’t a country where mengitis is a
lot . I also wished that they put how many nurses get effected by meningitis yarly .
That is probably it , all aroud th article was pretty good and well structured .
Paragraph 4:What do you learn about the Article, Journal , or Research and how you apply it in Nursing
Profession?
I larned that Patients with all forms of meningitis present with signs and symptoms of meningeal
inflammation/irritation and systemic infection. Common complaints usually include headache, fever,
chills, nuchal rigidity, vomiting, photophobia, and seizures. Depending on age, virulence of the strain,
and defense system of the host, patients can become critically ill if not promptly diagnosed and
treated.3
Infection with bacterial meningitis carries high mortality and morbidity rates with an overall fatality of
25% reported in adults.4 These patients can have an acute onset of common meningeal symptoms, as
listed above, which can progress rapidly to neurological deterioration. As the disease advances, macular
skin rash progressing to purpuric and ecchymotic lesions may be present due to petechial hemorrhage,
seen specifically in meningococcal disease.9 As the infection ensues, circulatory shock and death can
transpire, even if treated. Therefore, antibiotic therapy should be initiated within 30 minutes of
emergency department presentation for those suspected of bacterial meningitis.3
Viral meningitis is more prevalent, but causes less serious complications than bacterial meningitis.
Patients with viral meningitis commonly present with similar meningeal symptoms, which may be less
severe and appear flu-like in nature. They may complain of a history of an upper respiratory infection
that is accompanied by headache, stiff neck, anorexia, or generalized malaise.9 Depending on the
infecting organism, these symptoms may dissipate without treatment.
Clinical manifestation of fungal meningitis may be mild initially. Due to the encapsulated nature of the
organism, the body may not exhibit signs of infection until extensive neurological involvement has
occurred. Headache, low-grade fever, vomiting, and lethargy are primary symptoms that can occur and
may fluctuate throughout the course of illness.3 Once a patient becomes infected, a characteristic
feature of fungal infection is its tendency to recur, especially for patients who are immunosuppressed.7
Therefore, devastating outcomes can occur if patients aren't adequately treated with antifungal
medications.
Also I learned that Initial nursing assessment includes a thorough history, neurological exam, review of
systems, and vital signs. The nursing assessment must also focus on history of travel, previous infections,
medications, and sources of immunosuppression. The neurological exam consists of cranial nerve
assessment, level of consciousness, motor strength, sensory exam and evaluation of headache. Other
signs of meningeal irritation may include positive Kernig's sign, which is pain and hamstring resistance
that is elicited upon passive knee extension while patient is supine. Brudzinski's sign is positive if there's
an involuntary flexion of hips due to passive neck flexion while patient is supine.9(See Testing for
meningeal irritation.) Findings from a neurological exam may include altered mental status, confusion
and irritability, vision disturbances such as photophobia, cranial nerve deficits, and changes in level of
consciousness.
Positive Brudzinski's and Kernig's signs indicate meningeal irritation, a sign of meningitis.
Have your patient lie in the supine position. Then place your hand under his neck and flex it forward,
chin to chest. The test is positive if he flexes his knees and hips bilaterally. The patient will typically
complain of pain when his neck is flexed.
Have your patient lie in the supine position. Flex his hip and knee to form a 90-degree angle. Then
attempt to extend his leg. If he exhibits pain or resistance to extension and spasm of the hamstring, the
test is positive.
Also Nursing care needs to focus on patient's symptoms as they are presented. The primary treatment is
the timely administration of empiric antibiotics, even if an organism hasn't been initially identified.3
Antibiotics may be started, especially if meningeal symptoms are present, prior to CSF culture results.6,9
Basic care while in the intensive care unit (ICU) includes reducing the amount of stimulation, maintaining
proper body alignment with head straight and elevated to at least 30 degrees, frequent pain and
neurological assessment, close monitoring of vital signs, ensuring adequate cerebral perfusion pressure
(CPP), assessing and treating fever, maintaining standard precautions, and providing adequate skin care,
nutrition, and hydration throughout the hospital stay.9 Minimal noise levels and dim lights create a
more calming environment and can prevent agitation in the patient with meningitis. All these factors
can help prevent the devastating outcomes of organism invasion such as shock and increasing
intracranial pressure (ICP). If meningococcal meningitis is suspected, droplet precautions are
recommended until 24 hours after initiation of effective therapy.11 Any close contacts, including family
members, healthcare providers who did not wear masks, and anyone in close proximity to the patient,
need administration of prophylactic antibiotics within 24 hours after patient diagnosis.8
Medical interventions depend on whether the meningitis is bacterial, viral, or fungal in nature.
Bacterial treatment: Empiric intravenous antibiotics must be given for the specific organism endemic to
the region. When specific organisms are isolated, the appropriate antibiotic may then be started
intravenously. Initial empiric antibiotics include third generation cephalosporins such as ceftriaxone
(Rocephin), or fluoroquinolones such as ciprofloxacin (Cipro). According to researchers, the use of
glucocorticoids, such as dexamethasone (Decadron), with the initiation of the first antibiotic dose has
been shown to decrease unfavorable outcomes and mortality from bacterial meningitis with adults.
However, there's limited data on dexamethasone use in adults, and if given should be initiated with the
first dose of antibiotics for a limited number of days. Steroid use is controversial, and research is
ongoing. In a systemic review, experts suggest, “…routine steroid therapy with the first dose of
antibiotics is justified in most adult patients in whom acute community acquired bacterial meningitis is
suspected.”The major effect of dexamethasone is a decrease in the inflammatory response.
Viral treatment: Medical management for viral meningitis is mostly supportive based on symptoms. Bed
rest, adequate hydration, antipyretics, antiemetics, and analgesics are recommended. Antiviral
medications may be administered and are usually reserved for severe cases of infection caused by
herpes viruses.
Fungal treatment: Patients with fungal meningitis should be aggressively treated with antifungal
medications such as amphotericin B and fluconazole (Diflucan) given intravenously for several weeks.
Ref:
1. McGill F. Heyderman RS. Michael BD, et al. The UK joint specialist societies guideline on the diagnosis
and management of acute meningitis and meningococcal sepsis in immunocompetent adults. J Infect.
2016;72:405–38. [PubMed] [Google Scholar]
2. Khetsuriani N. Quiroz ES. Holman RC. Anderson LJ. Viral meningitis-associated hospitalizations in the
United States, 1988-1999. Neuroepidemiology. 2003;22:345–52. [PubMed] [Google Scholar]
3. Kupila L. Vuorinen T. Vainionpaa R, et al. Etiology of aseptic meningitis and encephalitis in an adult
population. Neurology. 2006;66:75–80. [PubMed] [Google Scholar]
5. Turtle L. Jung A. Beeching NJ, et al. An integrated model of care for neurological infections: the first six
years of referrals to a specialist service at a university teaching hospital in Northwest England. BMC
Infect Dis. 2015;15:387. [PMC free article] [PubMed] [Google Scholar]
6. van de Beek D. de Gans J. Spanjaard L, et al. Clinical Features and Prognostic Factors in Adults with
Bacterial Meningitis. N Engl J Med. 2004;351:1849–59. [PubMed] [Google Scholar]
7. Stockdale AJ. Weekes MP. Aliyu SH. An audit of acute bacterial meningitis in a large teaching hospital
2005–10. QJM. 2011;104:1055–63. [PubMed] [Google Scholar]
8. Attia J. Hatala R. Cook DJ. Wong JG. The rational clinical examination. Does this adult patient have
acute meningitis? JAMA. 1999;281:175–81. [PubMed] [Google Scholar]
9. Durand ML. Calderwood SB. Weber DJ, et al. Acute bacterial meningitis in adults: a review of 493
episodes. N Engl J Med. 1993;328:21–8. [PubMed] [Google Scholar]
10. Gillespie IA. McLauchlin J. Little CL, et al. Disease presentation in relation to infection foci for non-
pregnancy-associated human listeriosis in England and Wales, 2001 to 2007. J Clin Microbiol.
2009;47:3301–7. [PMC free article] [PubMed] [Google Scholar]
11. Thwaites G. Fisher M. Hemingway C, et al. British Infection Society guidelines for the diagnosis and
treatment of tuberculosis of the central nervous system in adults and children. J Infect. 2009;59:167–87.
[PubMed] [Google Scholar]
12. Moxon CA. Zhao L. Li C, et al. Safety of lumbar puncture in comatose children with clinical features of
cerebral malaria. Neurology. 2016;87:2355–62. [PMC free article] [PubMed] [Google Scholar]
13. Hase R. Hosokawa N. Yaegashi M. Muranaka K. Bacterial meningitis in the absence of cerebrospinal
fluid pleocytosis: A case report and review of the literature. Can J Infect Dis Med Microbiol.
2014;25:249–51. [PMC free article] [PubMed] [Google Scholar]
14. Spanos A. Jr Harrell FE. Durack DT. Differential diagnosis of acute meningitis. An analysis of the
predictive value of initial observations. JAMA. 1989;262:2700–7. [PubMed] [Google Scholar]
15. Brouwer MC. Thwaites GE. Tunkel AR. van de Beek D. Dilemmas in the diagnosis of acute
community-acquired bacterial meningitis. Lancet. 2012;380:1684–92. [PubMed] [Google Scholar]
16. Nigrovic LE. Kuppermann N. Macias CG, et al. Clinical prediction rule for identifying children with
cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA. 2007;297:52–60. [PubMed]
[Google Scholar]
17. Heinsbroek E. Ladhani S. Gray S, et al. Added value of PCR-testing for confirmation of invasive
meningococcal disease in England. J Infect. 2013;67:385–90. [PubMed] [Google Scholar]
18. Newcombe J. Cartwright K. Palmer WH. McFadden J. PCR of peripheral blood for diagnosis of
meningococcal disease. J Clin Microbiol. 1996;34:1637–40. [PMC free article] [PubMed] [Google Scholar]
19. Morales Casado MI. Moreno Alonso F. Juarez Belaunde AL, et al. Ability of procalcitonin to predict
bacterial meningitis in the emergency department. Neurologia. 2016;31:9–17. [PubMed] [Google
Scholar]
20. Vikse J. Henry BM. Roy J, et al. The role of serum procalcitonin in the diagnosis of bacterial
meningitis in adults: a systematic review and meta-analysis. Int J Infect Dis. 2015;38:68–76. [PubMed]
[Google Scholar]
21. Proulx N. Frechette D. Toye B. Chan J. Kravcik S. Delays in the administration of antibiotics are
associated with mortality from acute bacterial meningitis. QJM. 2005;98:291–8. [PubMed] [Google
Scholar]
22. Dellinger RP. Levy MM. Rhodes A, et al. Surviving sepsis campaign: international guidelines for
management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637. [PubMed]
[Google Scholar]
23. Alam N. Oskam E. Stassen PM, et al. Prehospital antibiotics in the ambulance for sepsis: a
multicentre, open label, randomised trial. Lancet Respir Med. 2018;6:40–50. [PubMed] [Google Scholar]
24. Kaewpoowat Q. Salazar L. Aguilera E. Wootton SH. Hasbun R. Herpes simplex and varicella zoster
CNS infections: clinical presentations, treatments and outcomes. Infection. 2016;44:337–45. [PubMed]
[Google Scholar]
25. Tunkel AR. Hartman BJ. Kaplan SL, et al. Practice guidelines for the management of bacterial
meningitis. Clin Infect Dis. 2004;39:1267–84. [PubMed] [Google Scholar]