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Author: Marjorie Lazoff, MD, Editor-in-Chief, Medical Computing Review

Marjorie Lazoff is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, American Medical Informatics Association, and Society for Academic Emergency Medicine

Editors: Mark S Slabinski, MD, FACEP, FAAEM, Mid-Atlantic Regional Director, Emergency Medicine Physicians, Ltd; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eric L Weiss, MD, DTM&H, Director of Stanford Travel Medicine, Medical Director of Stanford Lifeflight, Assistant Professor, Departments of Emergency Medicine and Infectious Diseases, Stanford University School of Medicine; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital

Author and Editor Disclosure

Synonyms and related keywords: inflammation of the leptomeninges, inflammation of the underlying subarachnoid cerebrospinal fluid, bacterial meningitis, meningococcal meningitis, pneumococcal meningitis, Neisseria meningitidis, N meningitidis, Streptococcus pneumoniae, S pneumoniae, Listeria monocytogenes, L monocytogenes, group B streptococci, Haemophilus influenzae, H influenzae, Haemophilus influenzae type b, H influenzae type b, brain edema, nuchal rigidity, fungalmeningitis, tuberculous meningitis, Kernig sign, Brudzinski sign, papilledema, increased intracranial pressure, increased ICP

Background

Meningitis is an inflammation of the leptomeninges and underlying subarachnoid cerebrospinal fluid (CSF). It can be useful to divide symptom onset into acute, subacute, and chronic categories. Unlike subacute (1-7 d) or chronic (>7 d) meningitis, which have myriad infectious and noninfectious etiologies, acute meningitis (<24 h) is almost always a bacterial infection caused by one of several organisms. Depending on age and general condition, these gravely ill patients present acutely with signs and symptoms of meningeal inflammation and systemic infection of less than 1 day's duration. Patients may decompensate quickly and require emergency care, including antimicrobial therapy, within 30 minutes of emergency department (ED) presentation.

Not all bacterial meningitis is acute. Approximately 75% of patients with bacterial meningitis present subacutely. These ill patients still require urgent ED diagnosis and care.

The emergence of resistant strains has prompted changes in antibiotic protocols in some countries, including the US. Apart from dexamethasone, neuronal cell protectants still hold only future promise as adjunctive therapy.

The challenges for emergency physicians when treating meningitis are to (1) identify and treat patients with acute bacterial meningitis, (2) assess whether a central nervous system (CNS) infection is present in those with suspected subacute or chronic meningitis, and (3) identify the causative organism. Bacterial meningitis must be excluded. Emergency physicians should be aware that future therapies will be based on improved understanding of the pathogenesis of acute bacterial meningitis and may include caspase inhibitors, antioxidants, poly (ADP-ribose) polymerase inhibitors, inhibitors of lipid peroxidation, and metalloproteinase inhibitors, in addition to antibiotics and steroids.

Pathophysiology

A number of factors influence the development of bacterial meningitis, including virulence of the strain, host defenses, and bacteria-host interactions.

Bacterial seeding usually occurs by hematogenous spread. In those without an identifiable source of infection, local tissue and bloodstream invasion by bacteria colonized in the nasopharynx may be a common source. Rarely, infected contiguous structures invade via septic thrombi or osteomyelitic erosion; meningeal seeding also may occur with a direct bacterial inoculate during trauma, neurosurgery, or instrumentation. Meningitis in the newborn is transmitted vertically from colonized pathogens in the maternal intestinal or genital tract or horizontally from nursery personnel or caregivers at home.

Once in the CSF, the paucity of antibodies, complement components, and white blood cells (WBCs) allows the bacterial infection to flourish. Bacterial cell wall components initiate a cascade of complement- and cytokine-mediated events that result in at least 3 critical events: increased permeability of the blood-brain barrier, cerebral edema, and presence of toxic mediators in the CSF. Replicating bacteria, increasing numbers of inflammatory cells, cytokine-induced disruptions in membrane transport, and increased vascular and membrane permeability perpetuate the infectious process and account for the characteristic changes in CSF cell count, pH, lactate, protein, and glucose. Exudates extend throughout the CSF, particularly to the basal cisterns, damaging cranial nerves (eg, cranial nerve VIII, with resultant hearing loss), obliterating CSF pathways (causing obstructive hydrocephalus), and inducing vasculitis and thrombophlebitis (causing local brain ischemia).

As intracranial pressure (ICP) continues to rise and brain edema progresses, CNS autoregulatory processes begin to fail. This pivotal event may occur when the transient increase in cerebral blood flow (CBF) reverses and begins to decrease. CBF reduction correlates with the patient's decreasing alertness and changes in mental status.

Without medical intervention, the cycle of decreasing CBF, worsening cerebral edema, and increasing ICP proceeds unchecked. Ongoing endothelial injury may result in vasospasm and thrombosis, further compromising CBF, and may lead to stenosis of large and small vessels. Systemic hypotension (septic shock) also may impair CBF, and the patient soon dies from systemic complications or from diffuse CNS ischemic injury.

The pathophysiologies of nonbacterial pathogens are less well understood. Fungal meningitis is thought to unfold in a manner similar to but less acute than bacterial meningitis.

Frequency

United States

The incidence of bacterial meningitis is 2-3 per 100,000. Recent statistics show an increase among persons aged 60 years and older independent of other factors. In 1995, incidence by major pathogens (all ages per 100,000) was as follows:

  • Streptococcus pneumoniae (1.1) in all except neonates
  • Neisseria meningitidis (0.6), usually local outbreaks among young adults, epidemics internationally, and increased incidence in late winter or early spring
  • Group B streptococci (0.3), in newborns
  • Listeria monocytogenes (0.2) in newborns, elderly, and immunocompromised
  • Haemophilus influenzae, type b (0.2) in unvaccinated children and adults

International

Meningococcal meningitis is endemic in parts of Africa, India, and other developing nations. Periodic epidemics occur in the so-called sub-Saharan "meningitis belt" as well as among religious pilgrims traveling to Saudi Arabia for the Hajj.

Mortality/Morbidity

Morbidity and mortality depend on pathogen, patient's age and condition, and severity of acute illness.

  • Among bacterial pathogens, pneumococcal meningitis causes the highest rates of mortality (21%) and morbidity (15%).
  • Mortality rate is 50-90% and morbidity even higher if severe neurologic impairment is evident at the time of presentation (or with extremely rapid onset of illness), even with immediate medical treatment.

Race

Statistically, blacks are at greater risk than other races, although race may not be an independent risk factor.

Sex

In neonates, male-to-female ratio is 3:1. No sex preference exists among adults.

Age

Median age is 25 years. In 1986, it was 15 months.

  • Excluding meningococcal meningitis, patients younger than 5 years and older than 60 years are at increased risk.
  • Newborns are at highest risk for acute bacterial meningitis. After the first month of life, the peak incidence is in infants aged 3-8 months.



History

Distinguishing acute, subacute, and chronic meningitis helps identify the pathogen. Approximately 25% of patients with bacterial meningitis present acutely within 24 hours of onset of symptoms. Other patients with bacterial meningitis and most patients with viral meningitis present with subacute neurologic symptoms developing over 1-7 days. Chronic symptoms lasting longer than 1 week suggest meningitis caused by some viruses as well as tuberculosis, syphilis, fungi (especially cryptococci), and carcinomatous meningitis.

  • Classic symptoms (not evident in infants or seen often in the elderly) include the following:
    • Headache
    • Nuchal rigidity (generally not present in children <1 y or in patients with altered mental status)
    • Fever and chills
    • Photophobia
    • Vomiting
    • Prodromal upper respiratory infection (URI) symptoms (viral and bacterial)
    • Seizures (30-40% in children, 20-30% in adults)
    • Focal neurologic symptoms (including focal seizures)
    • Altered sensorium (confusion may be sole presenting complaint, especially in elderly)
  • Symptoms in infants
    • Fever
    • Lethargy and/or change in level of alertness
    • Poor feeding and/or vomiting
    • Respiratory distress, apnea, cyanosis
  • Partially treated meningitis: As many as 40% of patients with meningitis were treated previously with oral antibiotics. Seizures may be the sole presenting symptom; fever and changes in level of alertness or mental status occur less commonly than in untreated meningitis.
  • Low-grade ventriculitis associated with ventriculoperitoneal shunt: Patients may have a less dramatic presentation than those with acute meningitis, with headache, nausea, minimal fever, and malaise.
  • Fungal meningitis: Headache, low-grade fever, and lethargy are the primary symptoms; the course may be mild with fluctuating symptoms, especially in immunocompromised patients.
  • Tuberculous meningitis: Fever, weight loss, night sweats, and malaise, with or without headache and meningismus are common symptoms; this infection may follow a protracted course with vague, nonspecific presentation.

Physical

Otherwise healthy patients within age extremes present with clinically obvious acute bacterial meningitis. In contrast, most patients with subacute bacterial meningitis present a diagnostic challenge. Systemic examination occasionally reveals a pulmonary or otitis media co-infection.

  • Signs of meningeal irritation
    • Nuchal rigidity or discomfort on neck flexion
    • Kernig sign: Passive knee extension in supine patient elicits neck pain and hamstring resistance.
    • Brudzinski sign: Passive neck or single hip flexion is accompanied by involuntary flexion of both hips.
  • Papilledema is present in only one third of meningitis patients with increased ICP; it takes at least several hours to develop.
  • Focal neurologic signs
    • Isolated cranial nerve abnormalities (principally III, IV, VI, VII) in 10-20% of patients
    • Associated with a dramatic increase in complications from lumbar puncture (LP) and portends a worse outcome
  • Systemic findings
    • Extracranial infection (eg, sinusitis, otitis media, mastoiditis, pneumonia, urinary tract infection) may be noted.
    • Arthritis is seen with N meningitidis, less commonly with other bacteria.
    • Nonblanching petechiae and cutaneous hemorrhages are seen classically with N meningitidis; however, these also can occur with other bacterial and viral infections.
    • Endotoxic shock with vascular collapse is characteristic of severe N meningitidis infection.
  • Altered mental status, from irritability to somnolence, delirium, and coma
  • Infants
    • Bulging fontanelle (if euvolemic)
    • Paradoxic irritability (ie, quiet when stationary, cries when held)
    • High-pitched cry
    • Hypotonia
    • Examine skin over entire spine for dimples, sinuses, nevi, or tufts of hair, which may indicate a congenital anomaly communicating with the subarachnoid space.

Causes

Meningitis is caused by the following pathogens in each age group:

  • Neonates - Group B or D streptococci, nongroup B streptococci, Escherichia coli, and L monocytogenes
  • Infants and children - H influenzae (48%), S pneumoniae (13%), and N meningitidis
  • Adults - S pneumoniae, (30-50%), H influenzae (1-3%), N meningitidis (10-35%), gram-negative bacilli (1-10%), staphylococci (5-15%), streptococci (5%), and Listeria species (5%)
  • Risk factors
    • Aged 60 years or older
    • Aged 5 years or younger, especially children with diabetes mellitus, renal or adrenal insufficiency, hypoparathyroidism, or cystic fibrosis
    • Immunosuppressed patients are at increased risk of opportunistic infections and acute bacterial meningitis. Immunosuppressed patients may not show dramatic signs of fever or meningeal inflammation.
    • Crowding (eg, military recruits and college dorm residents) increases risk of outbreaks of meningococcal meningitis.
    • Splenectomy and sickle cell disease increase the risk of meningitis secondary to encapsulated organisms.
    • Alcoholism and cirrhosis: Multiple etiologies of fever and seizures in these patients make meningitis challenging to diagnose.
    • Diabetes
    • Recent exposure to others with meningitis, with or without prophylaxis
    • Contiguous infection (eg, sinusitis)
    • Dural defect (eg, traumatic, surgical, congenital)
    • Thalassemia major
    • Intravenous (IV) drug abuse
    • Bacterial endocarditis
    • Ventriculoperitoneal shunt
    • Malignancy (increased risk of Listeria species infection)
    • Some cranial congenital deformities



Brain Abscess
Delirium Tremens
Encephalitis
Herpes Simplex
Herpes Simplex Encephalitis
Neoplasms, Brain
Pediatrics, Febrile Seizures
Pediatrics, Meningitis and Encephalitis
Subarachnoid Hemorrhage

Other Problems to be Considered

All causes of altered mental status and coma
Leptospirosis
Subdural empyema



Lab Studies

  • Complete blood count (CBC) with differential
  • Serum electrolytes to determine dehydration or syndrome of inappropriate secretion of antidiuretic hormone [SIADH])
  • Serum glucose as baseline for determining normal CSF glucose; may be low if glycogen stores are depleted or high in infected patients with diabetes
  • BUN and/or creatinine and liver profile to assess organ functioning and adjust antibiotic dosing
  • Coagulation profile and platelets in patients with chronic alcohol use, liver disease, or if disseminated intravascular coagulation (DIC) is suspected. (Patients may require platelets or fresh frozen plasma [FFP] prior to LP.)
  • Urinary electrolytes if SIADH is suspected
  • Serum cryptococcal antigen, especially if baseline is known (less diagnostic than India ink and CSF cryptococcal antigen)
  • Cultures prior to instituting antibiotics may be helpful if diagnosis is uncertain: blood (50% positive in meningitis caused by H influenzae, S pneumoniae, N meningitidis); nasopharynx, respiratory secretions, urine, and skin lesions.
  • Latex agglutination or counter immunoelectrophoresis (CIE) of blood, urine, and CSF for specific bacterial antigens is recommended occasionally if diagnosis is challenging or in patients with partially treated meningitis.
  • Serum test for syphilis is indicated if neurosyphilis is in differential diagnosis. (Cases have been documented of neurosyphilis CSF negative for Venereal Disease Research Laboratory test [VDRL].)

Imaging Studies

  • Head CT scan with contrast or MRI with gadolinium
    • Imaging is indicated in patients with evidence of head trauma, altered mental status, or focal findings.
    • Presence of papilledema and inability to fully assess fundi or neurologic status are indications for CT scan prior to LP.
    • Obtain blood cultures and initiate treatment before imaging studies and LP in patients with suspected bacterial meningitis.
    • Results may be normal or demonstrate small ventricles, effacement of sulci, and contrast enhancement over convexities.
    • Late findings include venous infarction and communicating hydrocephalus.
    • Rule out brain abscess, sinus or mastoid infection, skull fracture, and congenital anomalies.
  • Chest x-ray
    • As many as 50% of patients with pneumococcal meningitis also have evidence of pneumonia on initial chest x-ray.
    • This association occurs in fewer than 10% of patients with meningitis caused by H influenzae or N meningitidis and in approximately 20% of patients with meningitis caused by other organisms.

Procedures

  • Lumbar puncture (see Table 1 for interpretation of results)
    • Elevated opening pressure correlates with increased risk of morbidity and mortality in bacterial and fungal meningitis.
    • Take tube #1 to chemistry lab for glucose and protein.
    • Take tube #2 to hematology lab for cell count with differential.
    • Take tube #3 to microbiology and immunology lab for Gram stain, bacterial culture, acid-fast bacillus (AFB) stain and tuberculosis (TB) cultures, India ink stain and fungal cultures, CIE, VDRL, and cryptococcal antigen, if indicated.
    • Hold tube #4 for repeat cell count with differential, if needed (or for other subsequent studies not initially ordered).
    • Research correlates CSF cytokines in children with bacterial meningitis.
    • According to Seupaul, 3 diagnostic tests have clinically useful likelihood ratios for the diagnosis of bacterial meningitis in adults: CSF/blood glucose ratio less or equal to 0.4, CSF WBC count greater or equal to 500/L, and CSF lactate level equal or greater than 31.53.1
  • General patterns in CSF pressure measurement and analysis in bacterial, viral, and fungal (cryptococcal) meningitis may support a diagnosis. The most important diagnostic tests in the ED to rule out bacterial meningitis are a well-performed Gram stain and, if available, polymerase chain reaction (PCR) on the CSF of patients with suspected herpes simplex encephalitis.

Table 1. Comparison of CSF Findings by Type of Organism

Bacterial MeningitisViral Meningitis*Fungal Meningitis**
Pressure
5-15 cm H2O
IncreasedNormal or mildly increasedNormal or mildly increased in TB. May be increased in fungal. AIDS patients with cryptococcal meningitis have increased risk of blindness, death unless maintained at <30 cm.
Cell count
preterm: 0-25
term: 0-22
>6 months: 0-5
mononuclear
cells/mm3
No cell count result can exclude bacterial meningitis. Typically thousands of PMNs, but may be less dramatic or even normal (classically, in very early meningococcal meningitis and in extremely ill neonates). Lymphocytosis with normal CSF chemistries seen in 15-25%, especially when cell counts <1000 or if partially treated. Approximately 90% of patients with ventriculoperitoneal shunts have CSF WBC count >100 cells/mm3 are infected; CSF glucose usually normal, and organisms are less pathogenic. Cell count and chemistries normalize slowly (over days) with antibiotics.Usually <500 cells, nearly 100% mononuclear. Up to 48 hours, significant PMN pleocytosis may be indistinguishable from early bacterial meningitis; this is particularly true with eastern equine encephalitis. Presence of nontraumatic
RBCs in 80% of HSV meningoencephalitis, although 10% have normal CSF results
Hundreds of mononuclear cells
Micro
no organisms
Gram stain 80% effective. Inadequate decolorization may mistake H influenzae for gram-positive cocci. Pretreatment with antibiotics may affect stain uptake, causing gram-positive organisms to appear gram negative and decrease culture yield on average 20%.No organismIndia ink 80-90% effective for fungi; AFB stain 40% effective for TB (increase yield by staining supernate from at least 5 cc CSF)
Glucose
euglycemia: >50% serum
hyperglycemia: >30% serum wait 4 h after glucose load
DecreasedNormalSometimes decreased. Aside from fulminant bacterial meningitis, the lowest levels of CSF glucose are seen in TB, primary amebic meningoencephalitis, neurocysticercosis
Protein
preterm: 65-150
term: 20-170
>6 months: 15-45
mg/dL
Usually >150, may be >1000Mildly increasedIncreased; >1000 with relatively benign clinical presentation suggestive of fungal disease

*Some bacteria (eg, Mycoplasma, Listeria, Leptospira species, Borrelia burgdorferi [Lyme], spirochetes) produce spinal fluid alterations that resemble the viral profile. An aseptic profile also is typical of partially treated bacterial infections (more than 33% of patients have received antimicrobial treatment, especially children) and the 2 most common causes of encephalitis — the potentially curable HSV and arboviruses.
**In contrast, TB meningitis and parasites resemble the fungal profile more closely.



Prehospital Care

  • Evaluate and treat patient for shock or hypotension. Infuse crystalloid until euvolemic.
  • Consider seizure precautions. Treat seizures according to usual protocol.
  • Consider airway protection in patients with altered mental status.
  • For alert patients in stable condition with normal vital signs, administer oxygen, establish IV access, and transport rapidly to the ED.

Emergency Department Care

  • Acute meningitis: Regardless of presentation, perform CSF examination in acute meningitis to identify the specific organism and susceptibilities. Institute treatment as early as possible in the disease course, since delay in instituting treatment may contribute significantly to morbidity and mortality.
  • Subacute meningitis: Most patients with subacute bacterial meningitis present more of a diagnostic challenge than those with acute illness. In these patients, CSF examination constitutes the critical step in documenting the presence or absence of a CNS infection and type of infecting organism. If the patient's condition is serious and antibiotics have been given (arguably masking symptoms and hindering growth of organisms on culture), assume a bacterial infection is present, provide adequate antibiotic coverage, and admit the patient.
  • The patient's condition and ED organization may warrant a watchful wait for 8-12 hours, then a reexamination of the CSF (sooner if patient's condition deteriorates). If initial granulocytosis changes to mononuclear predominance, CSF glucose remains normal, and patient continues to look well, the infection is most likely nonbacterial.
  • In acutely ill patients, perform an LP (if appropriate) and administer first dose(s) of antibiotics +/- steroids within 30 minutes of presentation to ED.
  • Consider instituting ED triage protocol to identify patients at risk.
  • Initiate empiric therapy if LP cannot be performed within 30 minutes.
  • Begin empiric therapy prior to head CT scan if a focal neurologic deficit is present. If no mass effect is present, perform LP to obtain microbiology studies.
  • Treat systemic complications of acute bacterial meningitis: hypotension and/or shock, hypoxemia, hyponatremia (SIADH), cardiac arrhythmias and ischemia, cerebrovascular accident (CVA), and exacerbation of chronic diseases.
  • Look for signs of hydrocephalus and increasing ICP.
    • Manage fever and pain, control straining and coughing, avoid seizures, and avoid systemic hypotension.
    • In otherwise stable patients, sufficient care includes elevating head and monitoring neurologic status.
    • When more aggressive maneuvers are indicated, some authorities favor early use of diuresis (ie, furosemide 20 mg IV, mannitol 1 g/kg IV), provided circulatory volume is protected.
    • Hyperventilation in intubated patients, with a goal of PaCO2 25-30 mm Hg, may briefly lower ICP; hyperventilation with PaCO2 <25 mm Hg may decrease CBF disproportionately and lead to CNS ischemia.
    • Consider placing an ICP monitor in comatose patients or in those with signs of increased ICP.
    • With elevated ICP, remove CSF until pressure decreases by 50% and maintain at less than 300 mg water.
  • Seizure precautions in ED: Aggressively control seizures if present, since seizure activity increases ICP (ie, lorazepam 0.1 mg/kg IV and IV load with phenytoin 15 mg/kg or phenobarbital 5-10 mg/kg).
  • Controversy surrounds the administration of dexamethasone, which is given with or just before antibiotics.
    • Dexamethasone may interrupt the cytokine-mediated neurotoxic effects of bacteriolysis, which are at maximum in the first days of antibiotic use.
    • Recent meta-analysis of 10 years of clinical trials confirmed that dexamethasone decreases morbidity, especially incidence and severity of neurosensory hearing loss, for H influenzae meningitis and suggested comparable benefit for S pneumoniae meningitis in childhood. No adequate adult studies exist, although the pathophysiology is presumably similar. Meta-analysis suggests that limiting dexamethasone therapy to 2 days may be optimal. More recent studies continue to support the use of dexamethasone.
    • Theoretically, anti-inflammatory effects of steroids decrease blood-brain barrier permeability and impede penetration of antibiotics into CSF.
      • Decreased CSF levels of vancomycin have been confirmed in steroid-treated animals yet not in human studies.
      • Many authorities believe that all other antibiotics achieve minimal inhibitory concentrations (MICs) in CSF regardless of steroid use.
      • Dexamethasone may not clinically impede even vancomycin.
  • Ideal ED antibiotic therapy is based on a clearly identified organism on CSF Gram stain. Age and underlying conditions dictate empiric treatment in an ED patient without trauma or CNS instrumentation. Information presented in this chapter is taken from the 2003 edition of The Sanford Guide to Antimicrobial Therapy.
    • In neonates to age 1 month, the most common microorganisms are group B or D streptococci, Enterobacteriaceae (eg, E coli), and L monocytogenes.
      • Primary treatment is a combination of ampicillin (age 0-7 d: 50 mg/kg IV q8h; age 8-30 d: 50-100 mg/kg IV q6h) plus cefotaxime 50 mg/kg IV q6h (up to 12 g/d).
      • Alternative treatment is ampicillin (age 0-7 d: 50 mg/kg IV q8h; age 8-30 d: 50-100 mg/kg IV q6h) plus gentamicin (age 0-7 d: 2.5 mg/kg IV or IM q12h; age 8-30 d: 2.5 mg/kg IV or IM q8h).
      • Most authorities recommend adding acyclovir 10 mg/kg IV q8h for herpes simplex encephalitis.
    • In infants (1-3 mo), the most common microorganisms are those listed under neonates above and under older infant/child below.
      • Primary treatment is cefotaxime (50 mg/kg IV q6h, up to 12 g/d) or ceftriaxone (initial dose: 75 mg/kg, 50 mg/kg q12h up to 4 g/day) plus ampicillin (50-100 mg/kg IV q6h).
      • Alternative treatment is chloramphenicol (25 mg/kg PO or IV q12h) plus gentamicin (2.5 mg/kg IV or IM q8h).
      • If prevalence of cephalosporin-resistant S pneumoniae (DRSP) is >2%, add vancomycin (15 mg/kg IV q8h). Strongly consider dexamethasone (0.4 mg/kg IV q12h for 2 d or 0.15 mg/kg IV q6h for 4 d) starting 15-20 minutes before first dose of antibiotics.
    • In older infants or young children (3 mo - 7 y), the most common microorganisms are S pneumoniae, N meningitidis, and H influenzae.
      • Primary treatment is either cefotaxime (50 mg/kg IV q6h up to 12 g/d) or ceftriaxone (initial dose: 75 mg/kg, then 50 mg/kg q12h up to 4 g/d). If prevalence of DRSP is >2%, add vancomycin (15 mg/kg IV q8h). In countries with low prevalence of DRSP, consider penicillin G (250,000 U/kg/d IM/IV in 3-4 divided doses). Due to DRSP, penicillin G is no longer recommended in the US.
      • Alternative treatment (or if severely penicillin allergic) is chloramphenicol (25 mg/kg PO/IV q12h) plus vancomycin (15 mg/kg IV q8h).
      • Strongly consider dexamethasone (0.4 mg/kg IV q12h for 2 d or 0.15 mg/kg IV q6h for 4 d) starting 15-20 minutes before the first dose of antibiotics.
    • In an older child or an otherwise healthy adult (7-50 y), the most common microorganisms are S pneumoniae, N meningitidis, and L monocytogenes.
      • In areas where prevalence of DRSP is >2%, primary treatment is either cefotaxime (pediatric dose: 50 mg/kg IV q6h up to 12 g/d; adult dose: 2 g IV q4h) or ceftriaxone (pediatric dose: initial dose: 75 mg/kg, then 50 mg/kg q12h up to 4 g/day; adult dose: 2 g IV q12h) plus vancomycin (pediatric dose: 15 mg/kg IV q8h; adult dose: 750-1000 mg IV q12h or 10-15 mg/kg IV q12h). Some add rifampin (pediatric dose: 20 mg/kg/d IV; adult dose: 600 mg PO qd). If Listeria species is suspected, add ampicillin (50 mg/kg IV q6h).
      • Alternative treatment (or if severely penicillin allergic) is chloramphenicol (12.5 mg/kg IV q6h: not bactericidal) or clindamycin (pediatric dose: 40 mg/kg/day IV in 3-4 doses; adult dose: 900 mg IV q8h: active in vitro but no clinical data) or meropenem (pediatric dose: 20-40 mg/kg IV q8h; adult dose: 1 g IV q8h: active in vitro but few clinical data; avoid imipenem as it is proconvulsant).
      • In areas with low prevalence of DRSP, use cefotaxime (pediatric dose: 50 mg/kg IV q6h up to 12 g/d; adult: 2 g IV q4h) or ceftriaxone (pediatric dose: 75 mg/kg initial dose then 50 mg/kg q12h up to 4 g/d; adult: 2 g IV q12h) plus ampicillin (50 mg/kg IV q6h).
      • Alternative treatment (or if severely penicillin allergic) is chloramphenicol (12.5 mg/kg IV q6h) plus trimethoprim/sulfamethoxazole (TMP/SMX; TMP 5 mg/kg IV q6h) or meropenem (pediatric dose: 20-40 mg/kg IV q8h; adult dose: 1 g IV q8h).
      • Data are limited on the need for dexamethasone in adults. Sanford suggests administering it to persons with positive CSF Gram stain (indicates many bacteria), those in a coma, or those with increased CSF pressure with or without cranial nerve palsy. Administer first dose of dexamethasone (0.4 mg/kg q12h IV for 2 d or 0.15 mg/kg q6h for 4 d) 15-20 minutes before first dose of antibiotics.
    • In adults older than 50 years or adults with disabling disease or alcoholism, the most common microorganisms are S pneumoniae, coliforms, H influenzae, Listeria species, Pseudomonas aeruginosa, and N meningitidis.
      • Primary treatment if the prevalence of DRSP is >2% is either cefotaxime (2 g IV q4h) or ceftriaxone (2 g IV q12h) plus vancomycin (750-1000 mg IV q12h or 10-15 mg/kg IV q12h). If CSF Gram stain shows gram-negative bacilli, use ceftazidime (2 g IV g8h). In areas of low prevalence of DRSP, use cefotaxime (2 g IV q4h) or ceftriaxone (2 g IV q12h) plus ampicillin (50 mg/kg IV q6h).
      • Other options for treatment include meropenem, TMP/SMX, and doxycycline.
      • Data on the adult need for dexamethasone are limited. Sanford suggests administering dexamethasone to patients with positive CSF Gram stain (indicates many bacteria), those in a coma, or those with increased CSF pressure with or without cranial nerve palsy. Administer first dose of dexamethasone (0.4 mg/kg IV q12h for 2 d or 0.15 mg/kg q6h for 4 d) 15-20 minutes before first dose of antibiotics.
    • In HIV-positive/AIDS patients, consider cryptococci, Mycobacterium tuberculosis, syphilis, HIV aseptic meningitis, and Listeria species. If pathogen is unknown after an ED workup, draw a serum/CSF cryptococcal antigen and treat empirically as in adults older than 50 years pending results of all blood and CSF tests.
    • In patients who have had trauma or neurosurgery, the most common microorganisms are S pneumoniae (if CSF leak is present), Staphylococcus aureus, coliforms, and P aeruginosa.
      • Primary treatment is vancomycin (1 g IV q12h) plus ceftazidime (2 g IV q8h).
      • Alternative treatment is meropenem (1 g IV q8h).
    • In patients with infected ventriculoperitoneal (atrial) shunt, the most common microorganisms are Staphylococcus epidermidis, S aureus, coliforms, Propionibacterium acnes, and diphtheroids (rare). Consult a neurosurgeon, since early shunt removal is usually necessary for cure.
      • Pediatric dose - Either cefotaxime (50 mg/kg IV q6h) or ceftriaxone (50 mg/kg IV q12h if gram-negative bacillus) plus vancomycin (15 mg/kg/d IV q6h)
      • Adult dose - Vancomycin (1 g IV q12h) plus rifampin (600 mg PO qd). If CSF Gram stain shows gram-negative bacilli, use ceftazidime (2 g IV q8h) alone.
    • In patients with aseptic meningitis (CSF pleocytosis and normal CSF glucose, negative bacteria on Gram stain), the most common microorganisms are enteroviruses, human herpesvirus-2 (HHV-2), lymphocytic choriomeningitis virus (LCM), HIV, and other viruses. Other etiologies include drugs (NSAIDs, metronidazole, IV immunoglobulin) and, rarely, leptospirosis.
      • Manage by repeating LP if necessary to rule out partially treated bacterial meningitis.
      • Treatment options for leptospirosis are doxycycline (100 mg PO/IV q12h), penicillin G (5 million U IV q6h), or ampicillin (500 mg IV q6h).
    • For patients with symptoms lasting longer than 1 month with CSF pleocytosis, 40% have tuberculous meningitis, 7% cryptococci, 8% neoplastic, and 34% remain undiagnosed. Defer ED treatment until organism is identified.
    • Most authorities recommend adding vancomycin when treating patients of all ages in the US with suspected S pneumoniae meningitis to cover drug-resistant strains (36% of S pneumoniae, according to 1995 data).
    • Use of vancomycin may affect the decision to include dexamethasone (see above).
    • Increase standard cefotaxime pediatric dosage by 50-100 mg/kg/d to overcome intermediate cephalosporin resistance found in some S pneumoniae.
  • Prophylaxis for close contacts of patients with (suspected) N meningitidis
    • Indicated for those at increased risk, such as those who were in close contact with patient for at least 4 hours during the week before onset (eg, house mates, daycare center, cell mates) or were exposed to patient's nasopharyngeal secretions (eg, kissing, mouth-to-mouth resuscitation, intubation, nasotracheal suctioning). Spread is via respiratory droplets, not aerosols, hence close contact is required for prophylactic consideration.
    • H influenzae - Rifampin (pediatric dose: 10 mg/kg; adult dose: 600 mg PO bid) for 4 doses;
    • Neisseria - Rifampin (pediatric dose: children <1 mo - 5 mg/kg q12h; children > 1 mo - 10 mg/kg q12h; adult dose: 600 mg PO bid) for 4 doses
    • Alternative - Ciprofloxacin (adults) 500 mg PO single dose or ceftriaxone ( <15 y: 125 mg; >15 y: 250 mg) IM single dose
    • Primary treatment in many European countries - Spiramycin (pediatric dose: 10 mg/kg; adult dose: 500 mg) PO q6h for 5 days
    • Administer meningococcal vaccine only in established epidemics or in travelers to countries where meningococcal disease is currently epidemic. Vaccination does not replace prophylaxis.
  • Prophylaxis for household or daycare contacts of patients with (suspected) H influenzae type b is controversial. Most authorities treat contacts to protect unvaccinated children, especially those younger than 4 years who are at risk.
    • Indicated for those residing with the patient for at least 4 hours during the week before illness onset (if at least 1 unvaccinated child 4 years or younger, give prophylaxis to all except pregnant household contacts) or daycare contact with patient within 5-7 days (for single case: if all contacts at least 2 years, no prophylaxis; if unvaccinated children 2 years or younger attend, consider prophylaxis and vaccinate susceptible children. For 2 or more cases in 60 days: if unvaccinated children attend, prophylaxis recommended for children and personnel).
    • Rifampin (pediatric dose: 10 mg/kg; adult dose: 600 mg) PO q12h x 4 doses

Consultations

  • Neurology
  • Infectious diseases



Begin empiric antibiotic coverage according to age and presence of overriding physical conditions. Empiric therapy also depends on prevalence of DRSP. In the US, prevalence is considered high (>2-5%). Patients with severe penicillin (and presumed cephalosporin) allergies often require alternative therapy.

Drug Category: Antibiotics

Antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug NameAmpicillin (Marcillin, Omnipen)
DescriptionInterferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. This drug is given in place of amoxicillin in patients unable to take medication orally.
Adult Dose50-100 mg/kg IV q6h
Pediatric DoseNeonates <1 month
Days 0-7: 50 mg/kg IV q8h
Days 8-30: 50-100 mg/kg IV q6h
Infants to young adults: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Drug NameCefotaxime (Claforan)
DescriptionThird-generation cephalosporin that has broad-spectrum activity against gram-negative organisms, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms.
By binding to one or more of the penicillin-binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial replication.
Adult Dose2 g IV q4h
Pediatric Dose< 12 years: 50 mg/kg IV q6h up to 12 g/d
> 12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid may increase levels; coadministration with furosemide or aminoglycosides may increase nephrotoxicity
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy; has been associated with severe colitis

Drug NameGentamicin (Garamycin, Gentacidin)
DescriptionAminoglycoside antibiotic used for gram-negative bacterial coverage. Commonly used in combination with agent against gram-positive organisms and one that covers anaerobes. Not DOC. Consider using this aminoglycoside when penicillins or other less toxic drugs contraindicated, when bacterial susceptibility tests and clinical judgment indicate its use, and in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms.
Dosing regimens numerous and adjusted on basis of CrCl and changes in volume of distribution. Administer IV/IM.
Follow each regimen by at least trough level drawn on third or fourth dose (0.5 h before dosing); may draw peak level 0.5 h after 30-min infusion.
Adult DoseSerious infections and normal renal function: 3 mg/kg/d IV/IM q8h
Extended dosing regimen for life-threatening infections: 5 mg/kg/d IV q6-8h
Loading dose: 1-2.5 mg/kg IV q8h
Maintenance dose: 1-1.5 mg/kg IV q8h
Pediatric DoseNeonates:
Days 0-7: 2.5 mg/kg IV/IM q12h
Days 8-30: 2.5 mg/kg IV/IM q8h
Infants, older children, adolescents: Administer as in adults
ContraindicationsDocumented hypersensitivity; non–dialysis-dependent renal insufficiency
InteractionsOther aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; loop diuretics may increase auditory toxicity—irreversible hearing loss of varying degrees may occur (monitor regularly)
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsNarrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug NameCeftriaxone (Rocephin)
DescriptionThird-generation cephalosporin with broad-spectrum activity against gram-negative organisms, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms.
By binding to one or more of the penicillin-binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial replication.
Adult Dose2 g IV q12h
Pediatric Dose75 mg/kg IV initially followed by 50 mg/kg q12h up to 4 g/d
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid may increase levels; ethacrynic acid, furosemide, or aminoglycosides may increase nephrotoxicity
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in renal impairment; caution in breastfeeding women and allergy to penicillin

Drug NameChloramphenicol (Chloromycetin)
DescriptionBinds to 50 S bacterial-ribosomal subunits and inhibits bacterial replication by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Adult Dose50-100 mg/kg/d PO/IV divided q6h for 10 d; not to exceed 4 g/d
Pediatric Dose12.5-25 mg/kg IV q6h
ContraindicationsDocumented hypersensitivity
InteractionsWith concurrent barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase, causing toxicity; sulfonylureas may cause manifestations of hypoglycemia; rifampin may reduce serum levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; hydantoin may increase or decrease levels
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsUse only for indicated infections, or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)

Drug NameVancomycin (Vancocin)
DescriptionPotent antibiotic directed against gram-positive organisms and active against enterococcal species. Also useful in treatment of septicemia and skin structure infections. Indicated for patients who cannot receive, or have failed to respond to, penicillins and cephalosporins, or for those who have resistant staphylococcal infections. For penetrating abdominal injuries, combined with agent active against enteric flora and/or anaerobes.
To avoid toxicity, assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use CrCl to adjust dose in patients with renal impairment.
Adult Dose1 g IV q12h
Pediatric Dose10-15 mg/kg IV q8h
ContraindicationsDocumented hypersensitivity
InteractionsErythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced, when coadministered with nondepolarizing muscle relaxants
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in renal failure, neutropenia; red man syndrome caused by too rapid IV infusion (dose given over few minutes) but rarely happens when dose given over 2 h or by PO or IP route; red man syndrome not allergic reaction

Drug NameTrimethoprim/sulfamethoxazole (Bactrim)
DescriptionInhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, inhibiting folic acid synthesis. This results in inhibition of bacterial replication.
Adult Dose20 mg TMP/kg/d IV divided tid/qid
Pediatric Dose5-20 mg/kg/d IV divided tid/qid based on TMP
ContraindicationsDocumented hypersensitivity; megaloblastic anemia due to folate deficiency
Do not administer to infants <2 months
InteractionsMay increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); dapsone may increase blood levels of both drugs; concurrent diuretics increase incidence of thrombocytopenia purpura in elderly; may increase phenytoin levels; may potentiate effects of methotrexate in bone marrow depression; may increase hypoglycemic response to sulfonylureas; may increase levels of zidovudine
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsDiscontinue at first appearance of skin rash or sign of adverse reaction; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholics, elderly, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in G-6-PD-deficient individuals; AIDS patients may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Drug NameMeropenem (Merrem)
DescriptionBroad-spectrum carbapenem antibiotic that inhibits cell wall synthesis and has bactericidal activity. Effective against most gram-positive and gram-negative bacteria.
Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared to imipenem.
Adult Dose1 g IV q8h
Pediatric Dose20-40 mg/kg IV q8h
ContraindicationsDocumented hypersensitivity
InteractionsAlcohol may cause severe hypotension and cardiovascular collapse; calcium channel blockers may produce symptomatic orthostatic hypotension; aspirin may increase serum nitrate concentrations
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsPseudomembranous colitis and thrombocytopenia may occur, requiring immediate discontinuation of medication

Drug NameCeftazidime (Ceptaz, Fortaz)
DescriptionThird-generation cephalosporin with broad-spectrum activity against gram-negative organisms, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms.
By binding to one or more of the penicillin-binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial replication.
Adult Dose0.5-2 g IV/IM q8-12h
Pediatric DoseNeonates 1-4 weeks: 30 mg/kg IV q12h
Infants and children 1 month to 12 years: 30-50 mg/kg/dose IV q8h; not to exceed 6 g/d
ContraindicationsDocumented hypersensitivity
InteractionsAminoglycosides, furosemide, and ethacrynic acid may increase nephrotoxicity; probenecid may increase levels
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in renal impairment

Drug NameDoxycycline (Doryx, Bio-Tab)
DescriptionInhibits protein synthesis and thus bacterial growth by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Adult Dose100 mg IV q12h
Pediatric Dose< 8 years: Not recommended
> 8 years: 2-5 mg/kg/d IV in 1-2 divided doses; not to exceed 200 mg/d
ContraindicationsDocumented hypersensitivity; severe hepatic dysfunction
InteractionsAntacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate decrease bioavailability; can increase hypoprothrombinemic effects of anticoagulants; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsPhotosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug NamePenicillin G (Pfizerpen)
DescriptionInterferes with synthesis of cell wall mucopeptide during active replication, resulting in bactericidal activity against susceptible microorganisms.
Adult Dose5 million U IV q6h
Pediatric Dose50,000 U/kg IM; not to exceed 2.4 million U
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid can increase effects; tetracyclines can decrease effects
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsCaution in impaired renal function

Drug NameRifampin (Rifadin, Rimactane)
DescriptionInhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, interacts with bacterial RNA polymerase but does not inhibit mammalian enzyme. Cross-resistance has been shown only with other rifamycins.
Adult Dose600 mg PO/IV qd
Pediatric Dose10-20 mg/kg PO/IV; not to exceed 600 mg/d
ContraindicationsDocumented hypersensitivity
InteractionsInduces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; enalapril may increase BP; concurrent isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur)
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsObtain CBCs and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy associated with thrombocytopenia that is reversible if therapy discontinued as soon as purpura occurs; if treatment continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur

Drug NameAmphotericin B (AmBisome)
DescriptionDepending on concentration attained in body fluids and on susceptibility of fungus, can be fungistatic or fungicidal. Polyene antibiotic produced by strain of Streptomyces nodosus.
Changes membrane permeability by binding to sterols, such as ergosterol, in fungal cell membrane, causing variety of intracellular components to leak, leading to fungal cell death.
Adult Dose3 mg/kg/d IV of liposomal amphotericin B over approximately 120 min
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity
InteractionsAntineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity increased with cyclosporine
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsMonitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock

Drug NameFlucytosine (Ancobon)
DescriptionConverted to fluorouracil after penetrating fungal cells and inhibits RNA and protein synthesis. Active against candidal and cryptococcal species and used in combination with amphotericin B.
Adult Dose50-150 mg/kg/d IV divided q6h
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsAmphotericin B may increase toxicity; cytosine may inactivate flucytosine
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in bone marrow suppression; adjust dose in renal impairment

Drug NameFluconazole (Diflucan)
DescriptionSynthetic broad-spectrum bistriazole oral antifungal agent that is highly selective inhibitor of fungal cytochrome P-450 and sterol C-14 alpha-demethylation.
Adult Dose400 mg PO qd
Pediatric Dose6-12 mg/kg PO qd
ContraindicationsDocumented hypersensitivity; breastfeeding
InteractionsHydrochlorothiazides may increase levels; long-term use of rifampin may decrease levels; may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, cyclosporine, glyburide, and glipizide; may increase effects of anticoagulants
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMonitor patients who develop rashes during treatment; discontinue drug if lesions progress
May cause clinical hepatitis, cholestasis, and fulminant hepatic failure, including fatalities, especially when (1) patient has serious underlying medical condition such as AIDS or malignancy and (2) patient is taking multiple concomitant medications
Do not administer fluconazole in breastfeeding mothers



Further Inpatient Care

  • Admit to appropriate service.
  • If meningococcal meningitis is suspected, arrange for respiratory isolation for the first 24 hours and ensure appropriate ED personnel receive prophylaxis (see Patient Education section).

Deterrence/Prevention

  • One vaccine protects against 4 strains of N meningitidis. As of October 1997, the American College Health Association (ACHA) recommends that college students consider vaccination against meningococcal disease. This represents a departure from ACHA's previous policy to recommend vaccination only after discovering a college outbreak.

Complications

  • Immediate - Septic shock, including DIC, coma with loss of protective airway reflexes, seizures (30-40% of children, 20-30% of adults), cerebral edema, septic arthritis, pericardial effusion, and hemolytic anemia (H influenzae)
  • Subdural effusions - Reported in 39% of children aged 1-18 months with bacterial meningitis
    • Risk factors include young age, rapid onset of illness, low peripheral WBC count, and high CSF protein.
    • Seizures occur more commonly during the acute course of the disease, although long-term sequelae of promptly treated subdural effusions are similar to those of uncomplicated meningitis.
  • Delayed - Decreased hearing or deafness, other cranial nerve dysfunction, multiple seizures, focal paralysis, subdural effusions, hydrocephalus, intellectual deficits, ataxia, blindness, Waterhouse-Friderichsen syndrome, and peripheral gangrene

Prognosis

  • Prognosis depends on the pathogen, patient's age and condition, and severity of acute illness.
  • Patients with severe neurologic impairment on presentation or with extremely rapid onset of illness, even if treated immediately, have a 50-90% mortality rate and an even higher rate of morbidity.
  • Pneumococcal meningitis has the highest rates of mortality (21%) and morbidity (15%).

Patient Education

  • Health professionals recommend vaccinating all US college students against N meningitis.
  • See Treatment section for recommended prophylaxis for close contacts of patient with (suspected) N meningitidis or H influenzae type b meningitis.
    • Instruct all contacts to return to ED immediately at the first sign of fever, sore throat, rash, or symptoms of meningitis.
    • Rifampin prophylaxis only eradicates the organism from the nasopharynx; it is ineffective against invasive disease.
  • For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education articles Meningitis in Adults and Meningitis in Children.



Medical/Legal Pitfalls

  • Failure to diagnose bacterial meningitis among the top 5 ED malpractice claims
  • Failure to promptly institute treatment or failure to educate regarding follow-up care in previously discharged patient

Special Concerns

  • Neonate: Query the mother regarding intrapartum antibiotic prophylaxis and, if none, risk factors (eg, delivery <37 wk gestation, ruptured membranes 18 h or more, previously delivered child with group B streptococcal (GBS) infection, GBS bacteruria during pregnancy, intrapartum temp 100.4°F [38°C] or higher).
  • Travelers - Elicit recent travel history, as some Third World countries have outbreaks of meningococcal epidemics.
  • Geriatric patients - Elicit history of pneumococcal immunization.
  • Young adults - Routine immunization of this population has been the subject of controversy; however, this group is at greatest risk of exposure to epidemic meningococcal disease.
  • Revaccination is not recommended, but some authorities believe a booster may be required for patients at high risk (eg, nephrotic syndromes, renal failure, transplant recipients, splenectomy, HIV with last vaccine > 6 y ago).



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Meningitis excerpt

Article Last Updated: Nov 7, 2007