Volume I:
First Thirty Minutes
- Section 1
  Acute Care Algorithm/ Treatment Plans/ Acronyms
- Section 2
  Universal Approach
  - CALS Universal Approach To Emergency Advanced Life Support
- Section 3
  Steps 1-6
- Section 4
  Preliminary Impression/Focused Clinical Pathways
Volume II:
Resuscitation Procedures
Volume III:
Definitive Care

Infection 2: Meningitis Portal

PEDS: For newborn meningitis, see Vol III—NRP6 Meningitis/Sepsis in Newborn. For pediatric meningitis (ages 1 month to 7 years), see Vol III—PED9 Meningitis.

Meningitis refers to the inflammation of the meninges, a condition that can present in acute, subacute, and chronic states. In its acute virulent state, this condition can quickly lead to increased intracranial pressure (ICP), cerebral edema, neuronal damage, and death. Various agents and conditions cause meningitis, including infection. Bacteria, viruses, fungi, and parasites can infect the CNS and its fluid, the cerebral spinal fluid (CSF). The major concern in the emergency setting is identifying and treating acute bacterial causes of meningitis, which is a deadly disease with high morbidity.

Signs and symptoms that suggest meningitis include: stiff neck, photophobia, focal neurological deficits, Kernig's sign (passive knee extension of a supine patient causes neck pain and resistance to maneuver), Brudzinski's sign (passive neck or hip flexion produces involuntary bilateral hip flexion), seizures, petechiae and/or purpuric hemorrhages (a rash that classically occurs with Neisseria meningitidis but can also occur with other infections), and endotoxic shock (typically with Neisseria meningitidis).

However, there are less dramatic and non-specific signs and symptoms of meningitis such as fever, headache, altered mental status, or vomiting. Furthermore, immunocompromised patients (such as those with HIV/AIDS) may present without meningeal findings.^1,2 The team must have a high index of suspicion and an aggressive approach to this deadly disease.

Risk factors for infectious meningitis include:

recent exposure to a patient with meningitis
crowded living conditions (dorms, military)
the elderly
children with chronic disease
broadly defined immunosuppression, including conditions such as diabetes, alcoholism, splenectomy, malignancy
ventriculoperitoneal shunt patients
IV drug abusers
concomitant/source infection: sinusitis, pharygitis, otitis, rashes, parotitis (mumps), endocarditis, and others

The differential diagnosis of meningitis includes:

encephalitis
subarachnoid hemorrhage
CNS neoplasms
brain abscess
delirium tremens
subdural empyema
leptospirosis
all causes of altered mental status and coma

Arguably, the most important diagnostic test is the lumbar puncture (LP). However, given the wide and serious differential diagnosis, a head CT or MRI is always a consideration and interplays with the sequencing of the LP. The concern (besides misdiagnosis) is that a patient with unrecognized ICP may herniate their brain due to the LP procedure. The role of cranial imaging in patients suspected of having meningitis is controversial. Current recommendations include a scan before performing an LP in patients with altered mental status, head trauma, focal neuro findings, papilledema, history of a CNS lesion, recent seizure, or comorbidity.³ If a CT scanner is not readily available, it may be reasonable to proceed with the LP if the index of suspicion for meningitis is high and there are no signs or symptoms of increased ICP (and the exam does not obscure them).⁴ Do not let any diagnostic testing delay urgently needed antibiotic therapy.

During the LP, measure the opening pressure (elevated pressures correlate with increased morbidity and mortality) before collecting CSF for the following tests:

Tube 1—hematology: WBC count and differential
Tube 2—chemistry: protein and glucose
Tube 3—microbiology/immunology: Gram stain and bacterial cultures and as indicated other microbiology/immunology tests such as acid-fast bacillus (AFB) stain and tuberculosis cultures; India ink stain and fungal cultures; viral cultures; VDRL for syphilis; and antigenic tests such as countercurrent immunoelectrophoresis, latex agglutination tests, and cryptococcal antigen.
Tube 4—Repeat cell count and other tests not initially ordered. (This is your spare fluid that you may collect and hold).

In the following table, note that ranges and patterns are more salient than absolute values in this dynamic condition. (Values differ somewhat from author to author.)

Common CSF Findings in Meningitis⁵
	Normal	Bacterial	Viral	Fungal	Tuber- culosis	Abscess
Appearance	Clear	Clear or cloudy	Clear
Cell count	0 to 5	>1000	<1000	100 to 500	100 to 500	10 to 1000
% of PMNs	0 to 15%	>80%	<50%	<500%	<50%	<50%
% of lymphs	>50%	<50%	>50%	>80%	Monos	Varies
Glucose (mg/dL)	45 to 65	<40	45 to 65	30 to 45	30 to 45	45 to 60
CSF glucose/blood glucose	0.6	<0.4	0.6	<0.4	<0.4	0.6
Protein (mg/dL)	20 to 45	>150	50 to 100	100 to 500	100 to 500	>50
Opening pressure	6 to 20	>25	Variable	>20	>20	Variable
Gram stain	Negative	Positive	Negative

Other testing is done to help in the management of the specific clinical context, and may include a CBC, chest x-ray, glucose, urinalysis, BUN/creatinine, and electrolytes. Blood cultures and infectious site cultures may assume greater importance in those patients who are started on antibiotics prior to their scan/LP.

General initial management principles:

Use proper isolation precautions.
Protect the airway in patients with altered mental status. See Vol I—STEP 3 Initial Survey, PATHWAY 6 Adult Respiratory.
Treat hypovolemia and shock appropriately. See Vol I—STEP 3 Initial Survey and/or Vol III—TRAU CARE 1 Shock.
Institute seizure precautions and aggressively treat any seizure activity. See Vol III—NEU1 Status Epilepticus.
Do not delay antibiotic therapy. Strive to perform the LP and begin empiric antibiotic therapy within 30 minutes of arrival of patients with acute meningitis.
Begin antibiotic therapy for patients who need a scan and an LP before sending them for their scan.
Observe for CNS worsening while managing those conditions that can ICP:
- elevate head of bed
- control fever
- treat pain
- take measures to prevent/relieve straining and coughing
Consider invasive methods for monitoring and/or relieving ICP in patients who are worsening: invasive cranial monitors, ventricular drain placement, repeated LPs. Consult with specialists early and as needed.
Consider adjunctive steroid treatment: Dexamethasone 0.4 mg/kg IV every 12 hours for 2 days before or with parenteral antibiotics seems to benefits children infected with Hemophilus influenza and pneumococcal meningitis⁶; whether this benefit extends to adults is currently a matter of controversy. Use your clinical judgment in giving this therapy to adults. If you do so, consider substituting rifampin for vancomycin in the treatment regimens, as it is thought that steroids decrease vancomycin’s bactericidal activity in the CSF.⁷
Administer chemoprophylatic antibiotics for those exposed to the index case, with close surveillance of those at high risk for invasive meningococcal disease.
Initial empirical antibiotic therapy is based on bacteria variability by age group and patient comorbidity and by your local antibiotic resistance patterns. The doses assume normal renal function and are adult doses unless indicated otherwise. Be aware of interactions and side effects of antibiotics. Antibiotic selection may change depending on subsequent culture results.
Consult your infectious disease expert early.

Antibiotic Treatment for Immunocompetent Patients from 7 to 50 years

The most common causative organisms in this age group in the U.S. are Streptococcus pneumoniae and Neisseria meningitides.⁸(Haemophilus influenzae occurs in unvaccinated children and adults.) Empiric therapy recommendations⁹ include:

Adults:

Primary:
- cefotaxime 2 g IV every 4 to 6 hours and vancomycin 500 to 750 mg IV every 6 hours or
- ceftriaxone 2 g IV every 12 hours and vancomycin 500 to 750 mg IV every 6 hours.
Alternative:
- meropenem 1 g IV every 8 hours and vancomycin 500 to 750 mg IV every 6 hours.

PEDS: (See also dexamethasone.)

Primary:
- cefotaxime 200 mg/kg/day IV divided every 4 to 6 hours and vancomycin 15 mg/kg IV every 6 hours or
- ceftriaxone 100 mg/kg/day IV divided every 12 hours and vancomycin 15 mg/kg IV every 6 hours.
Alternative:
- meropenem 40 mg/kg IV every 8 hours and vancomycin 15 mg/kg IV every 6 hours.

Antibiotic Treatment for Patients Older than 50 years, Debilitated, Alcoholic, or with Impaired Cellular Immunity

The most common causative organisms in this age group in the U.S. are Streptococcus pneumoniae, Listeria monocytogenes, and aerobic gram-negative bacteria. (Some sources include Neisseria meningitidis in this cohort.)

Empiric therapy recommendations¹⁰ include:

Primary:
- cefotaxime 2 g IV every 4 to 6 hours and vancomycin 500 to 750 mg IV every 6 hours and ampicillin 2 g IV every 4 hours or
- ceftriaxone 2 g IV every 12 hours and vancomycin 500 to 750 mg IV every 6 hours and ampicillin 2 g IV every 4 hours.
Alternative:
- meropenem 1 g IV every 8 hour and vancomycin 500 to 750 mg IV every 6 hours.

Antibiotic Treatment: Other Patient Considerations¹¹

Post neurosurgery or post head trauma (Streptococcus pneumoniae, Staphylococcus aureus, coagulase-negative Staphylococcus, gram-negative bacilli): ceftazidime 2 g IV every 8 hours and vancomycin 750 mg IV every 6 hours.
Meningitis and infected VP shunt: (Staphylococcus aureus, coagulase-negative Staphylococcus, gram-negative bacilli, Propionibacterium acnes):
Adult: vancomycin 750 mg IV every 6 to 12 hours and Rifampin 600 mg PO once daily.
PEDS: cefotaxime 200 mg/kg/day IV divided every 4 to 6 hours and vancomycin 15 mg/kg IV every 6 hours or ceftriaxone 100 mg/kg/day IV divided every 12 hours and vancomycin 15 mg/kg IV every 6 hours.
Penicillin allergy. Note that some patients who are allergic to penicillin are allergic to cephalosporins. Several alternatives exist. (Chloramphenicol has failed drug resistant Streptococcus pneumoniae.)
Vancomycin 500 to 750 mg IV every 6 hours and trimethaprim/ sulfamethoxazole 15 to 20 mg/kg/day IV divided over every 6 to 8 hours
Chloramphenicol 50 mg/kg (up to 1 g) IV every 6 hours and trimethaprim/sulfamethoxazole 15 to 20 mg/kg/day IV divided over every 6 to 8 hours

Meningitis and HIV/AIDS Patients

CNS infections are common in HIV/AIDS patients, ranking only second to lung infections. As mentioned, the diagnosis of meningitis in this population may be problematic. Low CD4 counts (if known) are associated with serious and/or opportunistic disease. (If the count is not known, it may be best to assume the risk of opportunistic infection.) Besides Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitides, and aerobic gram-negative bacteria, other CNS infectious causes for this group include toxoplasmosis (most common), cryptococcus (Cryptococcus neoformans, very common), other fungi (Coccidioides immitis, Histoplasma capsulatum), viruses (CMV, herpes simplex, HIV), tuberculosis, and syphilis.^12,13

For HIV/AIDS patients with new CNS-related symptoms, including a different or prolonged headache, obtain a CT to rule out mass lesions and/or mass effect, as the neuro exam may be normal in patients with toxoplasmic mass lesions. After the CT has ruled out intracranial mass lesions, perform a LP. In addition to the usual CSF tests, obtain:

fungal, mycobacterial, and viral cultures
CSF cryptococcal antigen (sensitive, but delayed report)
CSF VDRL for syphilis
India ink stain for fungus

Note that CSF glucose, protein, WBCs, and the India ink stain may be normal with cryptococcal meningitis.

If an HIV/AIDS patient presents with a fulminant illness suggestive of acute bacterial meningitis, begin antibiotic therapy before scanning. (Many presentations of CNS infection in HIV/AIDS patients are indolent, and treatment in such cases can usually wait for the results of the CT/LP.) Empiric therapy recommendations¹⁰ include:

Primary:
- cefotaxime 2 g IV every 4 to 6 hours and vancomycin 500 to 750 mg IV every 6 hours and ampicillin 2 g IV every 4 hours or
- ceftriaxone 2 g IV every 12 hours and vancomycin 500 to 750 mg IV every 6 hours and ampicillin 2 g IV every 4 hours.
Alternative:
- meropenem 1 g IV every 8 hours and vancomycin 500 to 750 mg IV every 6 hours.

Specific treatment for suspected common opportunistic infections include:

For suspected cryptococcal infection or unclear etiology, start treatment with intravenous amphotericin B, which comes in different formulations and may involve test doses and increasing doses. See your formulary for direction.
Patients with presumed CNS toxoplasmosis infections should be admitted and treated with pyrimethamine and either sulfadiazine or clindamycin; however, treatment need not begin in the emergency setting.²⁴ Steroids are given if significant surrounding edema is involved.²⁵

Note that the treatment considerations mentioned do not include primary treatment for the HIV/AIDS virus itself, which is beyond the scope of this portal. Consult with an infectious disease specialist.

References

Chuck SL, Sande MA. Infections with Cryptococcal neoformans in the acquired immunodeficiency syndrome. N Engl J Med 1989 Sep 21;321(12):794-799.
Luft BJ, Hafner R, Korzun AH, et al. Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study Team. N Engl J Med 1993 Sep 30;329(14):995-1000.
Hasbun R, Aronin S, Quagliarello V. Treatment of Bacterial Meningitis. Comp Ther 1999;25(2):73-81.
Gopal AK, Whitehouse JD, Simel DL, Corey GR. Cranial computed tomography before lumbar puncture: a prospective clinical evaluation. Arch Intern Med 1999 Dec 13-27;159(22):2681-5.
Modified from EM Reports 1998; 19:94.
McIntyre PB, Berkey CS, et al. Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988. JAMA, 1997 Sep 17;278(11):925-31.
Hasbun et al.
The Medical Letter. Vol 43 (Issue 1111-1112) August 20, 2001.
2011 Sanford Guide to Antimicrobial Therapy, 41st edition.
2011 Sanford Guide to Antimicrobial Therapy, 41st edition.
2011 Sanford Guide to Antimicrobial Therapy, 41st edition.
Simpson DM, Berger JR. Neurologic manifestations of HIV infection. Med Clin North Am 1996 Nov;80(6):1363-1394.
Lane HC, Laughon BE, Falloon J, et al. NIH conference . Recent advances in the management of AIDS-related opportunistic infections. Ann Intern Med 1994 Jun 1;120(11):945-955.
Weller IV, Williams IG. ABC of AIDS: Treatment of Infections. BJM 2001 Jun 2;322(7298:1350-1354.

Infection 2: Meningitis Portal

References

Edition 13-October 2011