Central nervous system infections in the intensive care …svimstpt.ap.nic.in/jcsr/apr-jun14_files/1ra214.pdf · 107 ICU admission especially from India. Furthermore, many of the

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Received: 04 August, 2013.

INTRODUCTIONNeurological intensive care is an emergingspeciality globally. In developing countries likeIndia, however, facilities for intensive care arenot widely available.1 Further, very few centres,such as, tertiary care teaching hospitalsattached to medical colleges, and some of thecorporate sector hospitals in the country havefacilities for neurological intensive care. Therecent emergence of multidrug-resistantpathogens has added to the complexity of themanagement of central nervous system (CNS)infections. In this review an attempt has beenmade to provide an overview regarding themethodological issues, burden of the problem,diagnostic approach and key principlesunderlying the management of neurologicalinfections requiring admission to the ICU.

Central nervous system infections in ICUpatientsNeurological infections can be encountered inICU patients in the following situations. (i)CNS infections constitute an uncommon, butimportant aetiological cause requiringadmission to an intensive care unit (ICU). Inaddition, (ii) health-care associatedneurological infect ions may develop incritically ill patients admitted to an ICU forother indications. Furthermore, (iii) CNSinfections can develop as complications in ICUpatients including post-operative neurosurgicalpatients.2

Burden of the problemIndian scenario

Sparse published data are available on thespectrum of neurological infections requiring

Review Article:Central nervous system infections in the intensive care unit

B. Vengamma,1 M. Rajguru,1 B.C.M. Prasad,2 V.V. Ramesh Chandra2

Departments of 1Neurology, 2Neurosurgery, Sri Venkateswara Institute of Medical Sciences, Tirupati

ABSTRACTNeurological infections constitute an uncommon, but important aetiological cause requiring admission to an intensivecare unit (ICU). In addition, health-care associated neurological infections may develop in critically ill patientsadmitted to an ICU for other indications. Central nervous system infections can develop as complications in ICUpatients including post-operative neurosurgical patients. While bacterial infections are the most common cause,mycobacterial and fungal infections are also frequently encountered. Delay in institution of specific treatment isconsidered to be the single most important poor prognostic factor. Empirical antibiotic therapy must be initiated whileawaiting specific culture and sensitivity results. Choice of empirical antimicrobial therapy should take into considerationthe most likely pathogens involved, locally prevalent drug-resistance patterns, underlying predisposing, co-morbidconditions, and other factors, such as age, immune status. Further, the antibiotic should adequately penetrate theblood-brain and blood- cerebrospinal fluid barriers. The presence of a focal collection of pus warrants immediatesurgical drainage. Following strict aseptic precautions during surgery, hand-hygiene and care of catheters, devicesconstitute important preventive measures. A high index of clinical suspicion and aggressive efforts at identification ofaetiological cause and early institution of specific treatment in patients with neurological infections can be life saving.Key words: Central nervous system infections, Intensive care unit, Meningitis, VentriculitisVengamma B, Rajguru M, Prasad BCM, Ramesh Chandra VV. Central nervous system infections in the intensive care unit.J Clin Sci Res 2014;3:106-13. DOI: http://dx.doi.org/10.15380/2277-5706.JCSR.13.044.

Corresponding author: Dr B. Vengamma,Director, Senior Professor and Head,Department of Neurology, Sri VenkateswaraInstitute of Medical Sciences, Tirupati, India.e-mail: [email protected]

Central nervous system infections in the intensive care unit Vengamma et al

Online accesshttp://svimstpt.ap.nic.in/jcsr/apr- jun 14_files/1ra214.pdf

DOI: http://dx.doi.org/10.15380/2277-5706.JCSR.13.044

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ICU admission especially from India.Furthermore, many of the critically ill patientswith neurological infections variably getadmitted to the medical, neurological orrespiratory ICUs depending on the availabilityand prevailing admission policy. The variabilityand flexibility of policy for admitting patientswith neurological infections into ICUs shouldbe kept in mind while interpreting these data.

CNS infections requiring admission into anICU

In publication dating back to more than twodecades ago2 CNS infections constituted 2.3%to 10.5% of admissions into medical, surgicaland critical care ICUs in India. In anotherreport,2 neurological infections constituted 51%of admissions to a neurological ICU in SouthIndia. At a teaching hospital at Hyderabad, CNSinfections had accounted for 17% of admissionsto a neurological ICUs.3

Coma is a common indication for admissionto an ICU. In the Indian scenario CNS

infections constitute an important cause ofcoma. In published studies from India4,5

neurological infections accounted for 20% to57% of aetiological causes in coma patientsneeding admission to an ICU.

At our tertiary care teaching hospital,neurological infections accounted for 8.7% ofall ICU admissions (n=252) seen during thesix month period (Dec 2012 to May 2013) inthe medical ICU. The spectrum of patients withneurological infections requiring admission toICU at Sri Venkateswara Institute of MedicalSciences (SVIMS), Tirupati a tertiary careteaching hospital is shown in Table 1.

CNS infections developing as complicationsin ICU patients

Reliable epidemiological data regarding thetrue prevalence of health care-associatedintracranial infectious complications are notavailable. Sparse published data refer to postneuro-surgical infectious complications and

Table 1: Spectrum of neurological infections requiring admission to medical intensive care unit at SriVenkateswara Institute of Medical Sciences, Tirupati during a six-month period (Dec 2012 to May 2013)

Viral meningoencephalitis (n=6)Bacterial infections (n=3)

pyogenic meningitissubdural empyemacebrebral abscess

Mycobacterial (n=3)tuberculosis meningitistuberculomasmiliary tuberculosis with TBM

Protozoal (n=2)neurocysticercosistoxoplasmosis

Cryptococcal meningitis (n=1)Systemic infections with neurological involvement (n=6)

scrub typhusleptospirosiscerebral malariaenteric encephalopathydengue haemorrhagic feversystemic sepsis with multiorgan system failure

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CNS infections secondary to traumatic braininjury. The following conditions have beenconsidered to be important risk factors forhealth-care associated CNS infections: historyof neurosurgery; CSF leakage; recent headtrauma; presence of an evident focus ofinfection; and an immunocompromised state.

Patients with aneurysmal subarachnoidhemorrhage or severe traumatic brain injuryreceiving neurocritical care, especially, areconsidered to be at high risk for infectionsarising at distant foci, such as, endocarditis,blood stream infections, pneumonia, urinarytract infections, among others. In patientsundergoing invasive procedures, such as,craniotomy, intracranial device placement [fore.g., for intracranial pressure (ICP) monitoring,or diversion of the cerebrospinal fluid (CSF)from an obstructed ventricular system], health-care associated CNS infections (Table 2) havebeen known to develop.6 As per the National

Healthcare Safety Network, Division ofHealthcare Quality Promotion, Centers forDisease Control and Prevention (CDC/NHSN)6

definition of CNS infection, intracranialinfection must satisfy at least one of the criterialisted in Table 3. At least one of the criterialisted in Table 4 must be satisfied for diagnosingmeningitis or ventriculitis.6

Septic thrombosis of cerebral sinus and/or veinsis another documented cause of CNS infectionin ICU patients. Also, neuroinfections mayarise from more ‘exogenous’ sources such astransmission of pathogens from ICU personnelor the ICU environment; poor hand hygiene hasbeen identified to be one of the common andimportant causes of health-care associatedinfections in ICU patients.

CNS infection Vs catheter colonization/contamination

In critically ill ICU patients, it is important todistinguish CNS infections from catheter

Table 3: Criteria for the diagnosis of definition of CNS infection (intracranial infections)

1. Patient has organisms cultured from brain tissue or dura2. Patient has an abscess or evidence of intracranial infection seen during a surgical operation or on histopathologic

examination3. Patient has at least two of the following signs or symptoms with no other recognized cause: headache, dizziness,

fever (>38 oC), localizing neurologic signs, changing level of consciousness, or confusion, and at least one ofthe following:a. organisms seen on microscopic examination of brain or abscess tissue obtained by needle aspiration or by

biopsy during a surgical operation or autopsyb. positive antigen test on blood or urinec. radiographic evidence of infection, andd. diagnostic single antibody titer (IgM) or four-fold increase in paired sera (IgG) for pathogen; and if diagnosis

is made antemortem, physician institutes appropriate antimicrobial therapy

CNS = central nervous system; Ig = immunoglobulinSource: reference 6

Table 2: Commonly encountered health-care associated central nervous system infections in ICU patientsIntracranial infections

brain abscesssubdural or epidural infectionencephalitis

Meningitis or ventriculitisSpinal abscess without meningitis

ICU = intensive care unitSource: reference 6

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colonization and contamination. In thisscenario, a positive CSF culture in the absenceof abnormal CSF findings is suggestive of“contamination”; occurrence of at least twopositive CSF cultures with expected CSFprofiles and lack of clinical signs is suggestiveof “catheter colonization”.6,7 Further,pathological CSF findings in the absence ofpositive cultures is suggestive of device-relatedinfection; and a positive CSF cultureaccompanied by abnormal CSF findings orappropriate clinical scenario is suggestive ofhospital acquired meningitis. It is alsoimportant to distinguish CNS infection fromaseptic inflammation that occurs as aconsequence of tissue response to tissue injuryor stimulation by noninfectious agents.

CNS manifestations of systemic infections inICU patients

Recent trends have indicated that in additionto severe complicated falciparum malaria,enteric fever, systemic infections, such as,leptospirosis, scrub typhus are emerging asimportant causes for infections with CNSinvolvement needing ICU admission.

Diagnostic approach

A thorough clinical history and a meticulouslyconducted physical examination often providevaluable diagnostic clues to the aetiologicalcause of CNS infections in critically ill patients.Occurrence of fever and deterioration in thelevel of sensorium; evidence of raised

intracranial pressure in a comatose or sedatedpatient are important early clues suggestive ofCNS infection and should alert the clinicians.

A history of residence or travel from a malariaendemic area (malaria), occupations likefarmers working in paddy fields, sewerageworkers (leptospirosis) can help in diagnosticwork-up. In patients with altered sensorium, ahistory of prolonged fever with loose stools,gastrointestinal bleeding may raise thepossibility of enteric fever. Fever, headache,photophobia and vomiting may point tomeningitis. General physical examinationclues, such as, eschar (scrub typhus), petichealrash (dengue fever, falciparum malaria, scrubtyphus, leptopsirosis), subcutaneous nodules(neurocysticercosis), presence of hepaticdysfunction and /or acute kidney injury(falciparum malaria, leptopsirosis) may behelpful in identifying infections. While feveris often present in critically ill patients withneurological infections, some patients with life-threatening neurological infections can presentwithout fever.8 Fundus examination aftermydriatic administration can help in identifyingchoroid tubercles which are pathognomonic ofmiliary tuberculosis.9 Presence of lymphadeno-pathy, pleural effusion or ascites may point outto disseminated tuberculosis, especially inhuman immunodeficiency virus (HIV)seropositive individuals.10 Neurologicalexamination may reveal neck stiffness and othersigns of meningeal irritation or focal neuro-logical deficit.

Table 4: Criteria for the diagnosis of definition of CNS infection (meningitis or ventriculitis)

1. Patient has organisms cultured from CSF2. Patient has at least one of the following signs or symptoms with no other recognized cause: fever (>38 oC),

headache, stiff neck, meningeal signs, cranial nerve signs, or irritability and at least one of the following:a. increased white cells, elevated protein, and/or decreased glucose in CSFb. organisms seen on Gram’s stain of CSFc. organisms cultured from bloodd. positive antigen test of CSF, blood, or urine, ande. diagnostic single antibody titer (IgM) or four-fold increase in paired sera (IgG) for pathogen; and if diagnosis

is made antemortem, physician institutes appropriate antimicrobial therapy

CNS = central nervous system; CSF = cerebrospinal fluid; Ig = immunoglobulinSource: reference 6

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Tuberculosis meningitis (TBM) accounts formore than 70% of cases of neurologicaltuberculosis (TB) and is a great mimic. In spiteof TBM being a commonly encountered diseaseand widespread physician awareness, there isoften a delay in the diagnosis and institution ofspecific therapy for TBM. This is particularlytrue in the ICU setting.9,10 Fungal meningitisis an uncommon but important CNS infectionsseen in the ICU. Clinical presentation of fungalinfections may range from acute fulminantforms to chronic indolent forms causingsignificant morbidity and mortality. Low indexof suspicion, atypical presentation, and variableneuroradiologic findings result in a delayeddiagnosis of this condition. Fungal CNSinfections should be suspected in patients withpoorly controlled diabetes andimmunosuppressed patients. Common fungalinfections of CNS seen in the ICU includeCryptococcus meningitis (especially in HIV-positive patients), Mucormycosis (e.g.,

rhinocerebral mucormyco-sis), Aspergillosis,Scedosporium, Candida among others.2

Anthrax is a zoonotic disease which hasrecently been used as a weapon of bioterrorism.It is a rare but catastrophic cause of haemorr-hagic meningoencephalitis. The diagnosis isestablished by Gram stain of CSF smearexamination.11 Fungal meningit is, viralmeningitis and even TBM require extensivelaboratory facilities for confirmation ofaetiological diagnosis. However, these facilitiesare seldom available in India and most of thesepatients get treated empirically.

Imaging and laboratory diagnosis

Neuroimaging and CSF analysis constitute keyinvestigations in establishing the diagnosis ofCNS infection in critically ill pat ients.However, CSF examination may not always bepossible in critically ill patients due to thepresence of increased intracranial pressure,thrombocytopenia, bleeding tendency, among

Figure 1: Cerebellar abscess. A 22-year-old male presented with headache, vomitings and fever of 1 week duration.There was a history of decreased hearing left side associated with ear discharge. Plain (A) and contrast-enhanced(B) CT of the brain showed cerebellar abscess with hydrocephalus. The patient underwent suboccipital craniectomyand evacuation of cerebellar abscessCT = computed tomography

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Figure 2: Right-sided frontal abscess. A23-year-old male presented withheadache, fever, altered sensorium of 1week duration. Plain (A) and contrastenhanced (B) CT brain right frontalabscess. The patient underwent rightfrontal craniotomy and excision ofabscessCT = computed tomography

Figure 3: Left-sided temporalabscess. A 49-year-old malepresented with fever, headache of 15days and altered sensorium of 1 dayduration. MRI brain showed lefttemporal abscess. The patientunderwent left temporoparietalcraniotomy and excision of abscessMRI = magnetic resonance imaging

Central nervous system infections in the intensive care unit Vengamma et al

Figure 4: Left-sided parietal abscess. A 19-year-old lady presented with headache, vomiting and fever of 1 week,altered sensorium of 1 day and 2 episodes of generalized tonic clonic seizures. CT brain showed left parietal abscessCT = computed tomography

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Figure 5: Temporal subdural empyema. A 32-year-old male presented with a history of discharge fromleft ear and fever of 5 days duration. There was ahistory of 2 episodes of generalized tonic clonicseizures and 1 episode of vomiting. CT brain showedleft temporal subdural empyema. The patientunderwent left temporal craniotomy and evacuationof subdural empyemaCT = computed tomography

Figure 6: Cerebellar tuberculoma. A 11-year-old girl presented with headache, intermittent fever of 1 month. Overthe last 4 days, headache increased and patient developed vomiting. MRI brain was suggestive of midline cerebellartuberculoma. The patient underwent suboccipital craniectomy and excision of tuberculoma

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others and this may hamper the diagnosticwork-up.

Imaging modalities like ultrasonography,computed tomography (CT), magneticresonance imaging (MRI) can help inanatomical localization of the focus ofinfection (Figures 1,2,3,4,5 and 6). Identifica-tion of aetiological cause of neurologicalinfection requires lumbar puncture andcerebrospinal fluid examination bybiochemical, microbiological and moleculardiagnostic methods; blood culture and cultureof urine, pleural, ascitic and other body fluids.Serodiagnostic and molecular tests for denguefever, leptospirosis and scrub typhus infectionsmust be carried out.

Fungal, viral meningitis and even TBM requireextensive laboratory facilities for confirmationof aetiological diagnosis. However, thesefacilities are seldom available in India and mostof these patients get treated empirically.

Principles of management

In patients admitted to the ICU, monitoring iscarried out by noninvasive and if required,invasive methods. Care should be takenregarding fluid, electrolyte and nutritionalmanagement. A detailed description of thevarious therapeutic regimens available fortreatment of neurological infections is beyondthe scope of this review.

A high index of clinical suspicion andaggressive efforts at identificat ion ofaetiological cause and early institution ofspecific treatment in patients with neurologicalinfections can be life saving. Delay in institu-tion of specific treatment (e.g., antibiotictreatment) is considered to be the single mostimportant poor prognostic factor. Empiricalantibiotic therapy must be initiated whileawaiting specific culture and sensitivity results.Choice of empirical antimicrobial therapyshould take into consideration the most likelypathogens involved, locally prevalent drug-resistance patterns, underlying predisposing,

co-morbid conditions, and other factors, suchas age, immune status. Further, the antibioticshould adequately penetrate the blood-brain andblood-CSF barriers. The presence of a focalcollection of pus warrants immediate surgicaldrainage. Following strict aseptic precautionsduring surgery, hand-hygiene and care ofcatheters, devices constitute importantpreventive measures.

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