24

Infections of the central and peripheral nervous systems are relatively infrequent occurrences; however, when present, they can cause significant morbidity and mortality. Rapid diagnosis and appropriate treatment are paramount to preventing death and limiting disability in these patients.^1–3 This chapter provides information needed for prompt and accurate diagnosis and treatment of nervous system infections in the intensive care setting. The chapter will focus on the diagnosis and treatment of community-acquired infections of the nervous system, with a section near the end for the discussion of iatrogenic or hospital-acquired infections.

Nervous system infections can be divided into two broad categories: infection of the structures surrounding the nervous system (meningitis), and infection of the parenchyma of the brain and/or spinal cord (encephalitis, abscess).

The main and subtypes of infection are listed here, along with the information necessary for the neurologic intensive care unit.

Bacterial Infections of the Skull, Meninges, and Brain

Bacterial Meningitis

Risk factors Alcoholism, splenectomy, human immunodeficiency virus (HIV), diabetes, immunosuppression, malignancy, dialysis, and sickle cell disease4–7

Predisposing conditions Otitis media, sinusitis, bacteremia, pneumonia, and bacterial peritonitis^4–7

Most common organisms Dependent on age; most spread by respiratory transmission (Table 24–1)

Clinical presentation Headache, fever, nuchal rigidity, nausea/vomiting, neck or back pain; can have focal neurologic signs, altered level of consciousness, or seizures; onset of symptoms over hours to days^4–7

Physical exam signs Indicative of meningeal irritation

• Brudzinski’s sign: Passive flexion of the neck causes involuntary flexion of the knees and hips
  
• Kernig’s sign: Resistance to passive extension of the hip and knee

CSF, cerebrospinal fluid; GI, gastrointestinal; Hib, Haemophilus influenzae type B.

Differential diagnosis Includes viral meningitis, fungal meningitis, viral encephalitis, parenchymal abscess, epidural/subdural empyema, parasitic infection, neuroleptic malignant syndrome, and subarachnoid hemorrhage

Diagnosis and studies Cerebrospinal fluid (CSF) findings in bacterial meningitis: Opening pressure elevated, turbid, cloudy in appearance, red blood (cell) count (RBC) >200/mm³ with predominance of neutrophils, glucose decreased, and protein elevated (Table 24–2)

Imaging Has little role in the diagnosis of meningitis; is necessary to rule out hemorrhage, mass lesions, elevated intracranial pressure (ICP), or other nervous system infections

Lumbar puncture If ICP is elevated, then the risk of herniation after lumbar puncture is significantly increased; however, it may be valuable for the evaluation of clinical sequelae of infection, such as subdural empyema, hydrocephalus, and infarction.

Treatment Duration of treatment 10 to 14 days, depending on clinical response. Dexamethasone can be used to reduce meningeal inflammation and pain associated with nuchal rigidity, as well as the incidence of hearing loss in patients with Streptococcus pneumoniae or Haemophilus influenzae type B meningitis (Table 24–3)

Table 24–2 Cerebrospinal Fluid Analysis1–5

Parameter	Value
Opening pressure	4–15 mm Hg or 5.0–19.5 cm H2O
Clarity	Cloudy: indicative of bacterial infection; WBC > 200/mm3 for turbid CSF
Color	Reddish: subarachnoid hemorrhage via traumatic tap; RBC > 6000/mm3 to appear red Yellowish: increased protein levels—usually > 150 mg/dL Xanthochromia: spin sample in centrifuge
Cell count and differential	WBC < 5/mm3; may be higher in neonates ↑ neutrophils = bacterial infection ↑ lymphocytes = viral or fungal etiology RBC measured in successive tubes to differentiate subarachnoid hemorrhage from traumatic tap with clearing of CSF and decrease in the number of RBCs
Biochemistry: glucose and protein levels	Glucose blood glucose; CSF = normal values 45–60 mg/dL Glucose ↓ bacterial or fungal infections; normal in viral infections; protein = 15–40 mg/dL; ↑ not specific for type of meningitis
Gram’s stain/culture and bacterial antigen panels	Only type6–7

CSF, cerebrospinal fluid; RBC, red blood (cell) count; WBC, white blood (cell) count.

IV, intravenous; PCN, penicillin.

Osteomyelitis of the Skull

Differential diagnosis Tumor, trauma, and epidural/subdural empyema

Subdural Empyema

Subdural empyema is usually the result of direct extension of local infection (e.g., sinus infection), spread via diploic veins in skull.8 It can be seen in the epidural space and can be associated with osteomyelitis of the skull. It may also be postoperative or post-traumatic. There is a 50 to 60% morbidity rate, 10 to 20% mortality rate.⁹

Most common organisms Aerobic and anaerobic Streptococcus species, S. aureus, and gram-negative bacilli

Clinical presentation Fever, headache, nuchal rigidity, focal neurologic deficits, mental status changes, nausea/vomiting, and seizures

Differential diagnosis Bacterial meningitis, viral meningitis, fungal meningitis, parasitic infection, viral encephalitis, parenchymal abscess, subarachnoid hemorrhage, HIV, and neuroleptic malignant syndrome

Diagnosis and studies CT/MRI with contrast shows fluid collection with typical crescent shape as well as degree of mass effect or presence of midline shift. Lumbar puncture is not recommended due to suspected increased ICP and risk of herniation. When CSF is obtained, the findings are consistent with parameningeal infection. Usually there is an intraoperative culture swab (aerobic and anaerobic cultures).

Treatment Emergent surgical evacuation via craniotomy; however, bur holes can be used in critically unstable patients if purulent material is liquefied. Antibiotics consist of vancomycin 1 g IV q 12 hours plus ceftazidime 2 g IV q 8 hours plus metronidazole 500 mg IV q 6 hours. The 4 to 6 week course of antibiotics is adjusted depending on culture and sensitivities.

Brain Abscess

Brain abscess is a localized suppurative infection of the brain parenchyma,10 with a male predominance. There is a slightly higher rate in children 5 to 9 years and adults >60 years. The infection is usually due to hematogenous spread but can be a result of direct extension.

Predisposing conditions Otitis media, sinusitis, mastoiditis, oral infections, lung abscess, pulmonary abnormalities, cyanotic heart disease, bacterial endocarditis, penetrating trauma, and HIV^11–13

Most common organisms Streptococci species—aerobic, anaerobic, microaerophilic; Staphylococcus aureus most common secondary to trauma, surgery, or endocarditis;¹⁴ Staphylococcus epidermidis, Pseudomonas aeruginosa, Enterococcus, Bacteroides, Actinomyces, Nocardia associated with immunosuppression due to HIV disease;¹⁵ Mycoplasma tuberculosis (TB)—most common cause of brain abscess in some developing countries; Cryptococcus—usually seen with meningitis; Aspergillus—seen in immuno-suppressed patients from transplant; and Toxoplasma gondii.

Clinical presentation Headache, fever, altered level of consciousness, visual changes, focal neurologic deficits—specific symptoms depending on location of lesion

Differential diagnosis Bacterial meningitis, viral meningitis, fungal meningitis, parasitic infection, viral encephalitis, epidural/subdural empyema, intracerebral hemorrhage, subarachnoid hemorrhage, tumor, venous sinus thrombosis, and migraine headache

Diagnosis and studies Routine laboratory tests (CBC, basic chemistry panel) are usually not helpful. However, erythrocyte sedimentation rate (ESR) is usually elevated and can be used to follow the therapeutic response to antibiotics. C-reactive protein is also very sensitive and may be added as a test. Lumbar puncture is not usually indicated unless meningitis is suspected. When CSF is obtained, the findings are similar to other para-meningeal infections, such as elevated WBC, normal glucose, and elevated protein. Cultures are usually negative.

Imaging Contrast-enhanced CT or MRI scans show characteristic rim-enhancing lesion with necrotic center surrounded by white matter edema. It can be difficult to differentiate from primary glial and metastatic tumors. MR spectroscopy can improve diagnostic accuracy.¹⁶ The precise diagnosis of specific organisms requires pathological tissue from biopsy or resection.

Treatment See Tables 24–4 and 24–5

Viral Infections of the Meninges and Brain

Viral Meningitis

Differential diagnosis Bacterial meningitis, fungal meningitis, viral encephalitis, parenchymal abscess, epidural/subdural empyema, severe frontal or sphenoid sinusitis, vaccination, intrathecal administration of drugs, HIV, subarachnoid hemorrhage, migraine headache, parasitic infections, sarcoidosis, and neuroleptic malignant syndrome. The diagnosis of viral meningitis is usually one of exclusion.

Viral Encephalitis

Herpes simplex virus is a latent virus found in dorsal root ganglion; it is spread via the neuronal route. The majority of cases are caused by type I virus. CNS infection involves the mesial temporal lobes bilaterally, with one side affected worse than the other. Autopsy studies show a predilection of the olfactory and limbic systems.17

Clinical presentation Most common presentation is altered level of consciousness in the setting of acute febrile illness with possible focal neurologic signs.

Differential diagnosis Bacterial meningitis, viral meningitis, fungal meningitis, parasitic infection, epidural/subdural empyema, parenchymal abscess, tumor, subdural hematoma, HIV, lupus cerebritis, adrenal leukodystrophy, Reye’s syndrome, and neuroleptic malignant syndrome

Diagnosis and studies CSF analysis similar to aseptic meningitis; viral cultures of arboviruses and herpes simplex virus are available only at specialized laboratory. Electroencephalogram (EEG) can show characteristic periodic lateralizing epileptiform discharges (PLEDs) in the case of herpes simplex encephalitis (HSE).

Imaging Critical for diagnosis of encephalitis. Focal hyperintense lesions seen in inconsistent distribution on T2-weighted images and FLAIR (fluid attenuated inversion recovery) sequences on magnetic resonance imaging (MRI), especially in eastern equine encephalitis, asymmetric bitemporal distribution possibly with hemorrhage in HSE

Fungal Infections of the Meninges and Brain

Fungal Meningitis

Cryptococcus meningitis

Treatment Amphotericin B 0.5 to 0.8 mg/kg/day IV with flucytosine 37.5 mg/kg q 8 hours. Treat for 6 weeks. After treatment is completed, need to use fluconazole as maintenance 400 mg/ day for 2 to 3 months.

Histoplasma meningitis

Mostly found in Ohio and Mississippi river valleys; widely disseminated in soil. Respiratory transmission. Disseminated disease can be seen in immunosuppressed patients due to HIV, lymphoma, or iatrogenic cause. May cause mass lesions in parenchyma (histoplasmomas).18

Clinical presentation Similar to Cryptococcus

Differential diagnosis Similar to Cryptococcus

Diagnosis and studies CSF consistent with fungal meningitis; serology positive in 60 to 90% with CNS disease, cultures positive <30%

Treatment Amphotericin B 0.7 to 1.0 mg/kg/day IV Treat for 8 to 12 weeks. In patients with HIV, after treatment with amphotericin B is completed, use itraconazole 200 mg/day indefinitely. Despite aggressive treatment, there is ~20% mortality.

Coccidioides immitis meningitis

Diagnosis and studies CSF consistent with fungal etiology. The most reliable method of diagnosis is detection of complement fixing antibody in CSF.19 Culture is usually negative.

Treatment Fluconazole 400 to 800 mg/day; if no clinical response, then amphotericin B 0.1 to 0.3 mg/day intrathecal via Ommaya reservoir. Treat for ~2 years after CSF is normalized. For HIV patients, treatment is lifelong. Without treatment, Coccidioides meningitis is uniformly fatal within 2 years.²⁰

Blastomyces dermatitidis meningitis

Distributed along the Mississippi River; exists in moist soil. There is respiratory transmission. Most cases have evidence of systemic infection. CNS is involved in 6 to 33% of patients with disseminated disease.21 A mass lesion forms in the brain parenchyma more frequently than other fungal infections.

Clinical presentation Fever, cough, myalgias, arthralgias, and pleuritic chest pain

Differential diagnosis Bacterial meningitis, viral meningitis, bacterial abscess, and parasitic infection

Diagnosis and studies Culture from pulmonary secretions or tissue biopsy

Imaging CT/MRI is not usually helpful unless a mass lesion is present.

Treatment For pulmonary infection, use itraconazole 200 to 400 mg/day; if infection is severe, use amphotericin B 0.7 to 1.0 mg/kg/day. Treatment is for 6 months. CNS disease requires treatment with maximal dose amphotericin B.

Zygomycoses: Rhizopus, Mucor, and Rhizomucor

Aspergillus

Majority of cases occur in immunosuppressed transplant patients with prolonged neutropenia. It begins as pulmonary disease and disseminates to CNS via hematogenous spread. There can be direct extension from maxillary and ethmoid sinuses. It is associated with cavernous sinus thrombosis and the formation of mycotic aneurysms.

Tuberculosis of the Meninges and Brain

Tuberculosis Meningitis

Diagnosis and studies Purified protein derivative (PPD) skin testing;22 chest x-ray may show active or chronic TB infection. CSF analysis is the most useful diagnostic test;²³ it can demonstrate WBC elevation with lymphocytic predominance. Glucose is decreased, protein is elevated. Acid-fast smear positive <23% of the time; cultures positive in 40 to 70% of cases. Serological test to detect mycobacterial antigens and PCR to detect antibodies in CSF should be performed.

Imaging Contrast-enhanced CT/MRI can demonstrate meningeal inflammation as well as TB exudate around the basal cisterns. Magnetic resonance angiography (MRA) can detect vasculitic changes common with TB meningitis.

Treatment If TB meningitis is suspected, start antibiotic therapy empirically consisting of isoniazid 300 mg daily, rifampin 600 mg daily, ethambutol 15 to 25 mg/kg/day, pyrazinamide 25 mg/kg/day plus pyridoxine. Treat for 1 year. Can supplement with dexamethasone in patients with extreme neurologic compromise.²⁴ In patients with neurologic compromise, 70 to 80% survival rate; ~50% will have neurologic morbidity, including seizures, hemiparesis, hydrocephalus, and organic brain syndrome.

Tuberculoma

Spinal Tuberculosis

Clinical presentation Symptoms can be sudden or indolent; can include weakness, paresthesias, radiculopathy. Sensory level demonstrated in about two thirds of patients.25

Differential diagnosis Spinal epidural abscess, spinal cord tumor, spinal stenosis, disk herniation, spondylotic myelopathy, HIV, myelopathy, and multiple sclerosis

Diagnosis and studies PPD skin test. CSF consistent with parameningeal infection. Blood cultures are negative; however, biopsy/culture swab is necessary for definitive diagnosis.

Imaging MRI is modality of choice; it will show epidural or subdural exudate surrounding and compressing spinal cord.

Treatment Surgical decompression of spinal cord; incision and drainage of abscess. Antibiotic treatment for 1 year with usual anti-TB medications

Parasitic Infections

Cysticercosis

Echinococcus (Hydatid [cyst] Disease)

Organism is tapeworm that infects carnivorous animals (dog is primary definitive host). It is common in the Mediterranean; spread by fecal-oral route. CNS is involved in only 2% of cases.26 E. multilocularis is most common pathogen of the species.

Clinical presentation Headache, nausea/vomiting, seizures, hemiparesis, papilledema, cranial nerve palsies, and dysarthria

Diagnosis and studies Serological tests

Imaging CT/MRI can show cyst with sharp borders, without enhancement or associated edema.

Malaria

Syphilis

Lyme Disease

Multisystem disease caused by deer tick (Borrelia burgdorferi); most common arthropod-borne infection in the United States.27 Three clinical stages: (1) early stage, characterized by a distinctive rash known as erythema migrans; (2) dissemination stage, occurs days to weeks following infection; characterized by flulike symptoms called erythema chronicum migrans, which, if left untreated, can disseminate and involve cardiac and neurologic systems. This consists of a clinical triad of meningitis, cranial neuritis, and radiculopathy.28 It occurs in 10 to 15% of patients with stage 2 Lyme disease; (3) persistent infection, with symptoms that may not appear until weeks, months, or years after infection. Stage 3 typically involves joint pain. Other symptoms include arthritis and chronic neurologic problems, such as encephalopathy, ataxia, dementia, and neuropathy.

Diagnosis and studies Based on history and the presence of the typical macular rash. Antibody serologies cannot be detected until ~3 weeks postinfection; CSF consistent with aseptic (viral) meningitis.

Treatment Doxycycline 100 mg bid for 3 to 4 weeks. If neurologic abnormalities present, use ceftriaxone 2 g IV daily for 2 to 4 weeks.

Rickettsia/Ehrlichia

Amebic Encephalitis

Treatment Amphotericin B IV and intrathecal tetracycline and rifampin.29

Prion Disease, Creutzfeldt-Jakob Disease (similar to “mad cow” disease)

Clinical presentation Progressive dementia, fatigue, ataxia, myoclonus, tremor, rigidity, and focal neurologic deficits

CNS Infections in HIV Patients

Forty to 60% of all patients with acquired immunodeficiency syndrome (AIDS) will develop neurologic complications related to the disease.30 One third of patients with HIV will have neurologic symptoms as the presenting manifestation of the disease.³¹

Most common organisms Toxoplasma, primary B cell lymphoma, JC virus (causative agent for progressive multifocal leukoencephalopathy), Cryptococcus, and cytomegalovirus (CMV).

Toxoplasma Gondii

Ten percent of the general population of the United States has been infected with toxoplasma gondii.32 The major reservoir is domestic cats, spread to humans by fecal-oral route. Generally asymptomatic except in the setting of severe immunosuppression such as with advanced HIV disease when the CD4 count <200 or when reactivation of infection produces single or multiple abscesses in the brain parenchyma.

Clinical presentation Headache, fever, altered level of consciousness, lethargy, focal neurologic signs. Can also present with seizures or intracerebral hemorrhage.

Differential diagnosis Bacterial abscess, fungal abscess, parasitic infection, tumor, lymphoma, viral encephalitis, progressive multifocal leukoencephalopathy (PML), and CMV

Diagnosis and studies CSF analysis may be similar to that of parameningeal infection; however, there may be an elevated WBC count with neutrophilic predominance. The glucose may be normal and the protein elevated. There should be a serological test for Toxoplasma antibodies.

Imaging Contrast-enhanced CT/MRI will show characteristic round, rim-enhancing lesion, single or multiple, with associated white matter edema; difficult to differentiate from tumor or other types of abscesses radiologically

Lymphoma

Lymphoma develops in ~5% of patients with HIV disease.33 It is due to Epstein-Barr virus-associated B cell type. Approximately one third of patients will present with CNS disease.³⁴

Clinical presentation Lethargy, confusion, cognitive deficits, focal neurologic signs, seizures, and cranial nerve palsies

Differential diagnosis Toxoplasmosis, PML, other tumors (primary or metastatic), bacterial abscess, fungal abscess, parasitic infection, CMV, and viral encephalitis

Diagnosis and studies Routine laboratory tests are not usually helpful; no serological tests for identification. Diagnosis must be strongly considered in patients who do not respond to empiric treatment. For toxoplasmosis, definitive diagnosis requires biopsy.

Imaging Contrast-enhanced CT/MRI will show white matter lesions, possibly contrast enhancement. The lesion may cross the corpus callosum.

Treatment Chemotherapy; dexamethasone can cause tumors to “melt” away; whole brain radiotherapy. Median survival is 3 months.

Progressive Multifocal Leukoencephalopathy

PML is a progressive demyelinating disease, primarily seen in immunocompromised patients,35 such as those with HIV, lymphoma, chronic lymphocytic leukemia, lupus, and diseases caused by JC virus. Antibodies to JC virus can be detected in CSF.^36–38

Clinical presentation Progressive focal neurologic deficits and cognitive decline39,40

Differential diagnosis Multiple sclerosis, adrenal leukodystrophy, acute disseminated encephalomyelitis, toxoplasmosis, lymphoma, prion disease, and CMV

Diagnosis and studies CSF analysis usually normal. JC virus can be detected in CSF by serology and PCR. Definitive diagnosis requires biopsy, which is frequently diagnostic.

Imaging CT/MRI shows diffuse white matter disease; does not enhance with contrast

Treatment There is no proven effective therapy. Median survival is 15 months.

Cytomegalovirus

Fifty to 80% of the general adult population in the United States has been infected; most are asymptomatic. In nonimmunocompromised adults, infection is similar clinically to mononucleosis. Seen in patients late in the course of HIV disease: CD4 count <50; most common infection is rhinitis. Can involve spinal cord—characterized by ascending motor weakness, areflexia, and loss of bowel/bladder function.41 Similar to Guillain-Barré syndrome.

Clinical presentation Progressive deterioration of mental status and cognitive function, headaches, and seizures

Differential diagnosis Viral encephalitis, PML, lymphoma, toxoplasmosis, parasitic infection, and prion disease

Diagnosis and studies CSF is essentially normal; may have elevated protein. May test serology for CMV antigen by PCR. Can also perform specific viral cultures.

Imaging MRI can show nonspecific hyperintense signal changes on T2-weighted images and FLAIR sequences.⁴²

Treatment Gancyclovir 5 mg/kg IV q 12 hours plus foscarnet 90 mg/kg IV q 12 hours. Subsequently, treat HIV disease with antiretroviral therapy.

HIV Encephalopathy

Most common neurologic involvement in AIDS. Two thirds of patients with HIV/AIDS and one third of AIDS patients will have dementia at time of death.43 HIV causes diffuse brain atrophy.

Clinical presentation Altered level of consciousness, cognitive dysfunction, gait abnormalities, postural instability

Diagnosis and studies CSF usually nondiagnostic,44 although patient may have a slight elevation of WBC. Glucose is normal, protein is elevated. HIV antibodies can be detected in CSF.

Imaging CT/MRI will show generalized atrophy without specific findings. MRI may show hyperintense periventricular white matter abnormalities of T2-weighted images and FLAIR sequences.

Treatment Antiretroviral therapy. HIV disease can also cause an AIDS-related myelopathy and cranial neuropathies.

Spinal Infections

Spinal Epidural Abscess

More common in elderly, immunocompromised, and IVDA.45,46 Most common route of spread is hematogenous; most commonly located in lumbar region.

Risk factors Osteomyelitis, diskitis, diabetes, cancer, IVDA, alcohol abuse, and chronic renal failure.⁴⁷

Sources of infection (hematogenous): skin infection, endocarditis, bacteremia, urinary tract infection (UTI), dental abscess, respiratory infection, penetrating trauma, and psoas abscess. Can also occur from direct extension from vertebral body, disk space infection, or paraspinal/psoas abscess.⁴⁵ With hematogenous spread, abscess usually forms posteriorly in the spinal canal; if direct extension from osteomyelitis or diskitis, abscess usually forms anteriorly.^45,48 Neurologic deficits caused by epidural abscess are thought to be secondary to compression of neural elements combined with vascular thrombosis and infarction.^49–51

Most common organisms S. aureus, aerobic and anaerobic streptococci, Pseudomonas, Escherichia coli, and TB (common in chronic form)⁴⁷

Clinical presentation Back pain, fever; associated with nerve root or spinal cord dysfunction, such as weakness, pain, and loss of bowel/bladder control

Differential diagnosis Spinal TB, tumor, disk herniation, spinal stenosis, multiple sclerosis, HIV, myelopathy, and spondylotic myelopathy

Diagnosis and studies Routine laboratory tests are not usually helpful; most common laboratory abnormality is elevated ESR.52 Blood cultures are positive in 60% of cases.

Imaging Contrast-enhanced MRI is modality of choice that can demonstrate fluid collection as well as the degree of spinal cord compression. Thorough neurologic exam and MRI localize can the affected area.

Treatment In patients without neurologic deficits, use vancomycin 1 g IV q 12 hours, rifampin 600 mg daily, and cefotaxime 2 g IV q 8 hours for 6 to 8 weeks. Surgical evacuation is warranted if neurologic deficits are present; if surgical evacuation is done, follow with antibiotics and immobilization in a brace. Bracing is recommended in both cases. If abscess is located posteriorly, can perform laminectomies. If abscess is located anteriorly in the spinal canal, the patient may need corpectomy with anterior and possibly posterior stabilization. Mortality is 18 to 23%. Improvement of neurologic function postoperatively is rare.

Vertebral Osteomyelitis

Spinal infections account for 2 to 4% of cases of osteomyelitis,53 which is due to hematogenous spread. Fifty percent of cases are located in the lumbar spine.⁵⁴

Most common organisms S. aureus ~60%,⁵⁵ gram-negative bacilli (Pseudomonas, Proteus, E. coli), and fungal pathogens

Risk factors Diabetes, chronic steroid use, dialysis, IVDA, malnutrition, malignancy, advanced age, and immunosuppression^55,56

Sources of infection are commonly respiratory, bacteremia, UTI, soft tissue abscess, dental abscess, and postsurgical causes (~2.5%).^57,58 Spinal TB⁵⁹ has increased since the AIDS epidemic.

Clinical presentation Localized back pain unrelated to movement or position, fever

Differential diagnosis Important to differentiate osteomyelitis from neoplasms

Diagnosis and studies Most common laboratory abnormality is elevated ESR. Blood cultures are positive in only ~25% of cases. CT-guided biopsy should be performed for identification of organism if blood culture is negative.⁵⁵ Open biopsy may be necessary; specimens must be sent for bacterial and fungal cultures.

Imaging X-rays can show disk space narrowing and end-plate changes. Bone scan and MRI are the most sensitive studies for identifying vertebral osteomyelitis.60 MRI demonstrates hyperintense signal in the vertebral body on T2-weighted images.

Treatment Antibiotic therapy for 4 weeks combined with spinal bracing. Treat with anti-TB medications for 12 months if patient has Pott’s disease; also treat with spinal immobilization with bracing. Surgery is indicated if patient has neurologic deficit, spinal instability, a poor response to antibiotic therapy, or a nondiagnostic CT-guided biopsy.

Diskitis

Rare infection of nucleus pulposis with secondary involvement of end plate and vertebral body. Can be spontaneous or postprocedure. Risk factors are similar to those for vertebral osteomyelitis; must be differentiated from tumors that preferentially avoid the disk space.

Most common organisms S. aureus (spontaneous), S. epidermidis (postprocedure), Pseudomonas (IVDA), and E. coli

Clinical presentation Localized back pain, paraspinal muscle spasm, and radicular symptoms, such as pain, weakness, and paresthesias

Diagnosis and studies Elevated ESR. Blood cultures are positive in ~50% of cases.

Imaging X-ray can show destruction of disk space as well as end-plate irregularities. MRI can show involvement of disk space and is useful to rule out epidural abscess. CT-guided biopsy may be necessary to make definitive diagnosis.

Treatment Similar to treatment for osteomyelitis: antibiotics (vancomycin, rifampin, cefotaxime) for 4 to 6 weeks, immobilization with brace. Surgery is rarely required.

Iatrogenic Infections

Ventriculostomy

Infection is the most common complication associated with the use of external ventricular drains (incidence 0–27%).61,62 Prophylactic antibiotics should be directed toward gram-positive organisms.

Risk factors Hemorrhage, neurosurgery manipulation of drainage system, and duration of use⁶³

Most common organism: S. epidermidis⁶⁴

Diagnosis and studies CSF analysis and culture

Treatment Empiric antibiotics initially, including vancomycin, as well as broad gram-negative coverage, such as ceftazidime, ciprofloxacin, gentamicin, or piperacillin/tazobactam. Adjust antibiotics based on culture and sensitivity results. May need to include intrathecal vancomycin or gentamicin, depending on culture results

CSF Fistula

Three types: spontaneous, postsurgical, and post-traumatic. Two to 3% of patients with head injury developed CSF fistulas,65 of which 70% stop spontaneously within 1 week. Common sites of leakage include mastoid air cells, frontal sinus, cribriform plate, and sphenoid sinus.

Most common organisms S. pneumoniae, S. aureus, P. aeruginosa, and Enterobacteriaceae⁶⁶

Diagnosis and studies CSF analysis and culture. Coronal CT with thin cuts after intrathecal contrast can be helpful for localizing leaks in the skull base.

Treatment Elevate head of bed (HOB) >45 degrees at all times. Acetazolamide 250 mg qid to decrease CSF production, as well as lumbar drain, should be strongly considered. Lumbar drain provides excellent CSF diversion and allows easy access to CSF for frequent analysis. Surgical repair is indicated for persistent leaks. For infected fluid, use vancomycin 1 g IV q 8 hours with ceftazidime 2 g IV q 8 hours for 14 days, or use for 1 week after CSF normalizes. Change to nafcillin/oxacillin if not methicillin-resistant S. aureus (MRSA). Add gentamicin, pipericillin/tazobactam, or ciprofloxacin for Pseudomonas.

Shunt Infection

Accepted infection rate is 5 to 7%.67 There is an increased risk of seizures and mortality after infection. Fifty percent of infections are within 2 weeks, 70% within 2 months. Skin is most common source.

Risk factors Length of procedure and young age

Wound Infections

Wound infections represent a 1 to 5% risk after laminectomy.68 Degree of infection ranges from superficial to full thickness with wound dehiscence.

Risk factors Increasing age, diabetes, obesity, and chronic steroid use

Most common organisms S. aureus

Clinical presentation Pain, erythema, and purulent discharge at incision site

Diagnosis and studies Wound swab, culture, and sensitivity; should include aerobic and anaerobic cultures

Treatment Superficial infection: use first-generation cephalosporin or antistaphylococcal penicillin. Deep infection: use vancomycin/ceftazidime. Treat 10 to 14 days; adjust antibiotics based on culture and sensitivity results. Need irrigation and drainage of deeper infections with antibiotic pulse irrigation, followed by tension-free closure utilizing retention sutures.

Nosocomial Infections

Nosocomial infections account for >20% of hospital infections.69 The normal physical and chemical barriers are altered by trauma, surgery, endotracheal tubes, nasogastric tubes, invasive catheters, monitoring devices, and drains.

Most common infections: pneumonia, urinary tract infection, sinusitis, and bacteremia, as well as wound infections⁷⁰

Pneumonia

Most common nosocomial infection in the intensive care unit (ICU).71 There is increased incidence of pneumonia with prolonged endotracheal intubation and mechanical ventilation.

Risk factors Endotracheal intubation and aspiration⁷²

Most common organisms In ventilator-associated pneumonia, S. aureus.⁷³ Most common in the neurosurgical population: Pseudomonas, family Enterobacteriaceae, Acinetobacter.⁷⁴

Treatment Empiric antibiotics as recommended by the American Thoracic Society: fluoroquinolone, aminoglycoside, or third-generation cephalosporin combined with antipseudomonal and anti-MRSA agents⁷⁵

Urinary Tract Infection

Second most common infection in the ICU.76 UTI accounts for ~40% of all infections.⁷⁷

Risk factors Gender (female) and duration of use of catheter

Most common organisms E. coli, proteus, Pseudomonas, and yeast⁷⁸

Sinusitis

Most common organisms S. aureus, gram-negative bacilli, Pseudomonas, and Streptococcus.79 If untreated, can lead to osteomyelitis, subdural or epidural empyemas, meningitis, or abscess.⁸⁰

Bacteremia

Bacteremia represents 13% of nosocomial ICU infections; 90% are related to central venous catheters (CVCs).81 The alternative to a CVC is a percutaneously inserted central catheter, which decreased the incidence of complications and infections compared with central lines.82

Most common organisms S. epidermidis, S. aureus, Pseudomonas, and Enterobacter⁸³

Treatment If bacteremia is suspected, replace existing CVC. Empiric antibiotics should include vancomycin plus broad gram-negative coverage.⁸³