7 Fevers and Infections in the Neuro-ICU



Deena M. Athas, Amna Sheikh, and Jacqueline S. Urtecho


Abstract


Fever, both infectious and noninfectious, is a common occurrence in neuro-critical care unit (neuro-ICU). This chapter will discuss key components in diagnosis and management of some of the most common infectious and noninfectious causes of fever in the neuro-ICU.




7 Fevers and Infections in the Neuro-ICU




7.1 Brain



7.1.1 Meningitis


Meningitis is inflammation of the leptomeninges which consist of three layers (dura, arachnoid, and pia mater) which surround the brain and spinal cord. There are various causes of meningitis (Table 7‑1).


























Table 7.1 Various causes of meningitis

Bacteria


Viral


Fungal


Tubercular


Noninfectious


S. pneumoniae


N. meningitidis


H. Flu


L. monocytogenes


Aerobic gram (−) bacilli


HSV


VZV


Enterovirus


HIV


Arboviruses (West Nile)


Lymphocytic choriomeningitis


Cryptococcus


Coccidioides


Histoplasma


Aspergillosis


Mycobacteria


Malignancy


Medications/drugs (NSAIDs, IVIG, antibiotics, antiepileptic medications)


Autoimmune diseases


Abbreviations: HIV, human immunodeficiency virus; HSV, herpes simplex virus; IVIG, intravenous immunoglobulin; NSAIDs, nonsteroidal anti-inflammatory drugs; VZV, varicella-zoster virus.




Signs/Symptoms

Most patients present with one or more of the following symptoms:




  • Headache



  • Fever



  • Stiff neck



  • Nausea/Vomiting



  • Rash (petechial or vesicular)



  • Altered mental status



  • Sensitivity to light or sound



  • Physical examination findings of:




    • Brudzinski’s sign—flexion of the knees and hips upon neck flexion



    • Kernig’s sign—flexion of the knees and hips to 90 degrees, and then extension of knees causes pain and resistance



Risk Factors



  • Age



  • Living conditions



  • Medical conditions/diseases



  • Exposure



  • Travel



Workup


Laboratory Studies



  • Complete blood count (CBC), chemistry, coagulation panel, blood cultures, and liver function



  • Human immunodeficiency virus (HIV), Lyme, Lupus Ab, Purified protein derivative (PPD), Rapid Plasma Reagin (RPR) or Fluorescent treponemal antibody absorption (FTA-ABS)



  • Lumbar puncture (LP) sending cell count and culture can help to narrow the diagnosis (Table 7‑2). For patients on anticoagulants or antiplatelet agents other than aspirin, a hematology consultation can be considered prior to reversal recommendations. Do not delay antibiotics if the LP is delayed.














































































Table 7.2 CSF profiles by cause

Test




Viral


Fungal


Tubercular


Appearance


Clear


Purulent or clear


Clear


Clear to fibrous


Opaque, cob-web formation


Opening pressure


Normal <20 mm Hg


Elevated


Normal


Normal to elevated


Normal to elevated


WBC


0–8/mm3


>1,000/mm3


<100 to 1,000/mm 3


100–500/mm3


Variable


Cell differential


Lymphocyte and monocytes


Predominance of PMN


Lymphocytes


Lymphocytes


Lymphocytes


Protein


15–45 mg/dL


100–500 mg/dL


Normal to elevated


50–250 mg/dL


Elevated


100–500 mg/dL


Elevated


100–500 mg/dL


Glucose


50–80 mg/dL


<40 mg/dL


50–80 mg/dL


30–45 mg/dL


<50 mg/dL


CSF:serum glucose


0.6


< 0.4


>0.6


<0.4


<0.4


Organisms


None


S. pneumoniae, Neisseria, H. Flu, Listeria, S. aureus, Gram (–) bacilli


HSV-2, VZV, Enterovirus, HIV, West-Nile


Crypto, Coccidioides, Histoplasma, Aspergillosis


Mycobacteria


Abbreviations: CSF, cerebrospinal fluid; HIV, human immunodeficiency virus; HSV-2, herpes simplex virus 2; VZV, varicella-zoster virus.



Imaging

Computed tomography (CT) scan of brain is not recommended routinely prior to the LP. According to the Infectious Disease Society of America, a CT scan should be performed prior to performing the LP when any of the following conditions apply (Table 7‑3).
































Table 7.3 Conditions when patients should obtain CT of head prior to performing lumbar puncture. (Adapted from Tunkel et al. 3 )

Conditions


Details


Abnormal neurologic exam


Nonreactive pupils, arm/leg drift, gaze deviation, cranial nerve palsy, aphasia


Altered mental status


Inability to follow commands or answer questions


Papilledema


Presence of papilledema suggests increased ICP


Seizure


Within 1 week


Immunocompromised state


HIV/AIDS, cancer, any immunosuppressive therapy, post-transplantation


History of prior CNS disease


Mass lesion (tumor/abscess), large stroke, etc.


Abbreviations: AIDS, acquired immunodeficiency syndrome; CNS, central nervous system; CT, computed tomography; HIV, human immunodeficiency virus; ICP, intracranial pressure.




7.1.2 Acute Bacterial Meningitis



Epidemiology

According to Centers for Disease Control and Prevention (CDC), bacterial meningitis affects 4,000 people every year worldwide. Common causative organisms include: Streptococcus pneumoniae (61%) and Neisseria meningitidis (16%). Group B streptococcus (14%), Haemophilus influenzae (7%), and Listeria monocytogenes (2%).



Diagnosis

All patients with suspicion of bacterial meningitis should get immediate blood cultures and LP (lumbar puncture) and antibiotics started without significant delay. Fig. 7‑1 details the algorithm for suspected bacterial meningitis.

Fig. 7.1 Management algorithm for adults with suspected bacterial meningitis. 3 (Adapted from Tunkel A, et al. Practice guidelines for the management of bacterial meningitis.)



Treatment

Empiric antibiotics should be started as soon as possible. Broad-spectrum antibiotics are chosen initially based on risk factors or age (Table 7‑4). As specific pathogens are identified, the antibiotic of choice should be narrowed. Dexamethasone (10 mg IV every 6 hours) should be started 10 to 20 minutes prior to first dose of antibiotics whenever pneumococcal meningitis is suspected. 27 Steroids should be continued for 2 to 4 days when pneumococcal meningitis is confirmed. If LP results are not consistent with bacterial meningitis then steroids should be discontinued. Antibiotics can be continued until cultures are finalized.











































Table 7.4 Antibiotic therapy for meningitis based on predisposing factors. (Adapted Practice Guidelines for bacterial meninigitis. 3 )

Predisposing factor


Common bacteria


First-line antibiotic therapy


Alternative antibiotic therapy


Age: 2–50 years


N. meningitidis


S. pneumoniae


Third-generation cephalosporin


Vancomycin plus third-generation cephalosporin (ceftriaxone or cefotaxime)


Penicillin G, ampicillin, chloramphenicol, fluoroquinolone or aztreonam


meropenem, fluoroquinolone


Age: >50 years


S. pneumoniae,


N. meningitidis,


L. monocytogenes,


aerobic gram-negative bacilli


Vancomycin + ampicillin + third-generation cephalosporin (ceftriaxone or cefotaxime)



Basilar skull fracture


Penetrating trauma



S. pneumoniae, H. influenzae, Group A β-hemolytic streptococci


S. aureus, coagulase-negative


staphylococci, aerobic gram-negative bacilli (including P. aeruginosa)


Vancomycin + third-generation cephalosporin


Vancomycin + cefepime or Vancomycin + ceftazidime or Vancomycin + meropenem



Post-neurosurgical procedure


Aerobic gram-negative bacilli (including P. aeruginosa), S. aureus, coagulase-negative staphylococci (especially S. epidermidis)


Vancomycin + cefepime or Vancomycin + ceftazidime or Vancomycin + meropenem



CSF shunt


Coagulase-negative staphylococci (especially S. epidermidis), S. aureus, aerobic gram-negative bacilli (including P. aeruginosa), Propionibacterium acnes


Vancomycin + cefepime or Vancomycin + ceftazidime or Vancomycin + meropenem



Abbreviation: CSF, cerebrospinal fluid.




7.1.3 Aseptic Meningitis


Meningitis with clinical symptoms but negative bacterial cultures is called aseptic meningitis. Some of the more common causes of aseptic meningitis include:




  • Viruses: Enterovirus, HIV, herpes simplex virus (HSV), mumps, Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and adenovirus



  • Fungal infections: Cryptococcal infection and coccidioidal infection



  • Spirochetes: Lyme and syphilis



  • Leptomeningeal neoplasm



  • Drug-induced meningitis: Nonsteroidal anti-inflammatory drugs (NSAIDs), intravenous immunoglobulin (IVIG), antibiotics, and antiepileptic drugs



Diagnosis

LP should be done in all patients with suspected meningitis (Fig. 7‑1).



Treatment

All patients with suspected meningitis should be started on antibiotics until bacterial causes are ruled out.



7.1.4 Viral Meningitis


It is the most common form of meningitis but less severe than bacterial meningitis. Enteroviruses (coxsackievirus, echovirus, non-polio enteroviruses) which occur in the summer and fall are the most common cause of viral meningitis.



Treatment

Most cases are self-limited and resolve within 7 to 10 days. Generally, most patients can be managed with supportive treatment (antipyretics, IV fluids, pain medications, etc.). Antiviral treatment is required for some viruses such as HSV-2 and varicella-zoster virus (VZV) which are treated with acyclovir and HIV which is treated with anti-retrovirals.



7.1.5 Fungal Meningitis


Although relatively rare in the United States, they can occur in patients who are immunocompromised. Risk factors include organ transplantation, chemotherapy, or chronic steroid use. They present in a subacute or chronic fashion. Fungal meningitis does not spread person to person but rather patients inhale the spores which then spread from the lungs to the brain or spinal cord. Special attention should be paid to patients who have recently moved and may have been exposed based on their prior geographic location. Table 7‑5 notes some of the more common fungal infections according to the CDC.





































Table 7.5 Common fungal infections and treatment

Fungi


Transmission


Treatment


Cryptococcus


Soil


Bird droppings


Decaying wood


IV Amphotericin B + 5-Flucytosine x 2 weeks then oral fluconazole


Coccidioides


Soil in the southwest United States, Central and South America



Oral fluconazole induction


IV fluconazole with IT Amphotericin B for patients who fail oral therapy


Histoplasma


Bird/bat droppings


Central and Eastern USA


IV Amphotericin B with transition to oral itraconazole or fluconazole


Aspergillosis


From sinusitis, IVDA


IV Voriconazole or Amphotericin B


Blastomyces


Moist soil


Decaying wood/leaves


Midwest, Southcentral, and Southeast USA


IV Amphotericin B


Candida


Colonized on body, hematogenous spread


Amphotericin B + 5-Flucytosine




7.1.6 Ventriculitis


Inflammation of ependymal lining of cerebral ventricles due to infection is called ventriculitis.



Etiology



  • Causes include meningitis, cerebral abscess, trauma, external ventricular drains, intraventricular shunts, and intrathecal chemotherapy 31



  • Common causative organisms include staphylococcus species, gram-positive skin flora, gram-negative rods, and S. pneumoniae



Incidence

Ventriculitis rates ranges from 0 to 45% in the setting of intraventricular catheter. 25



Clinical Features

Fever, seizures, nuchal rigidity, new headache, 1 photophobia, nausea, lethargy, altered mental status, erythema, and tenderness over the tubing in patients with ventriculoperitoneal shunt (VPS). Pleuritis in cases of ventriculopleural shunt infection, peritonitis, abdominal pain, abdominal fluid collections in cases of ventriculoperitoneal shunt infection, 2 , 3 and blood stream infection and endocarditis in cases of ventriculoatrial shunt infection.



Diagnosis



  • According to Infectious Diseases Society of America (IDSA) guidelines 1 diagnosis of a cerebrospinal fluid (CSF) drain infection




    • Single or multiple positive CSF culture with pleocytosis, hypoglycorrhachia, and increasing cell count and clinical symptoms are ventriculitis and meningitis.



  • However, abnormalities in CSF cell count and glucose/protein may not be reliable indicators of infection, and normal CSF does not exclude infection.



  • If cultures are negative initially, they should be held for at least 10 days for slow growing organisms.



  • If a CSF device (including shunt, intrathecal pump, deep brain stimulatory, vagal nerve stimulator or associated hardware) is infected then current recommendations are to remove the infected device. Any device/shunt that is removed should be sent for culture.



  • In addition to CSF cultures, blood cultures should be obtained for any patient with a ventriculoatrial shunt and should be considered for patients with a ventriculoperitoneal or ventriculopleural shunt.



Imaging



  • Magnetic resonance imaging (MRI) with gadolinium is recommended for anyone with suspected CSF device infection.



  • CT of head with contrast can be considered an alternative if MRI is unavailable or contraindicated.



  • Abdominal imaging with CT of chest/abdomen or ultrasound of the abdomen should be completed in patients with peritoneal or pleural shunts and abdominal or pleuritic chest pain.



Treatment



  • Includes antibiotic therapy and removal of infected shunt or device (Table 7‑6).



  • Once a specific pathogen is identified, antibiotics should be narrowed (Table 7‑7).



  • Duration of antibiotic is between 10 and 14 days depending on the pathogen, can extend to 21 days for some gram-negative bacilli. Duration should be determined after the last positive CSF culture.














Table 7.6 Empiric antibiotic coverage in patients with suspected healthcare-associated ventriculitis/meningitis

No beta-lactam allergy or carbapenem allergy


With serious beta-lactam or carbapenem allergy


Vancomycin + antipseudomonal beta-lactam agent (cefepime, ceftazidime, or meropenem)


Vancomycin + Aztreonam or Ciprofloxacin








































Table 7.7 Antimicrobial selection based on organism and sensitivity

Specific antimicrobial agents based on pathogen


Pathogen


Antimicrobial agent


Methicillin-susceptible S. aureus


Nafcillin or oxacillin (unless beta-lactam allergy then vancomycin can be alternative)


Methicillin-resistant S. aureus


Vancomycin


Second-line therapy would be linezolid, daptomycin, or trimethoprim-sulfamethoxazole if unable to use vancomycin


Coagulase-negative staphylococci


Vancomycin


Rifampin: this agent should be added in combination, if sensitivities allow


Linezolid or daptomycin or trimethoprim-sulfamethoxazole can be used for patients unable to use beta-lactams or vancomycin



P. acnes


Penicillin G


Gram negative bacilli (non-pseudomonal)


Enterobacter


Klebsiella


Citrobacter


Serratia


H. influenzae


Proteus


Neisseria


Based on sensitives and CNS penetration


Ceftriaxone or cefotaxime



Pseudomonas


Cefepime,


ceftazidime, or


meropenem


Alternative would be aztreonam or a fluroquinolone


Acinetobacter


Meropenem


If carbapenem resistant, can use colistimethate sodium or polymyxin B


Candida


Liposomal Amphotericin B with 5-flucytosine


Aspergillus or Exserohilum


Voriconazole

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Feb 6, 2021 | Posted by in NEUROLOGY | Comments Off on 7 Fevers and Infections in the Neuro-ICU

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