Setting: ED
CC: “My head hurts.”
VS: BP: 145/92 mm Hg; P: 108 beats/minute; T: 102.8°F; R: 23 breaths/minute
HPI: A 31-year-old man comes to the ED with 1 day of severe fever, headache, and neck stiffness. He is very uncomfortable and is lying on the stretcher with a pillow over his face. He has been nauseated and vomited several times.
PMHX: none
Medications: none
What should you do next?
a. Perform a physical examination.
b. Give ceftriaxone and vancomycin IV.
c. Give ceftriaxone, vancomycin, and dexamethasone IV.
d. Order a head CT.
e. Order blood cultures.
Answer e. Order blood cultures.
If this is “real life,” order blood cultures, antibiotics, and the steroids even before you do the physical. This is because the presentation of a chief complaint with fever, headache, stiff neck, and what seems to be photophobia is so clear for meningitis that getting the antibiotics ready in the shortest period of time is the most important thing you can do. However, remember that on CCS, the instant you order a test or a treatment, it is considered “administered” by the program. That means you just want to get the blood cultures to determine the specific organism involved rather than having the antibiotics given before an LP.
The “instant” you order something on CCS, it is considered “Administered.” Ordered = Administered on CCS
Timing is critical with meningitis! Move fast!
PE:
General: very uncomfortable man. Trying not to move.
Neurological: no focal deficits; cranial nerves intact
Musculoskeletal: neck inflexible
HEENT: photophobia present
Initial Orders:
LP
What do you expect to see on CSF if this is viral meningitis?
a. Protein extremely high, lymphocytes elevated
b. Glucose low, neutrophils elevated
c. Protein mildly elevated, lymphocytes elevated
d. Thousands of white cells with 90% neutrophils
Answer c. Protein mildly elevated, lymphocytes elevated
You should know what you expect to see on the test you order before it is done. Viral meningitis has an elevated white blood cell (WBC) count that is mostly lymphocytes. The CSF protein can be normal or mildly elevated. Bacterial meningitis has a predominance of neutrophils.
Head CT Before LP
• Focal neurological findings
• Papilledema
• Severe confusion (makes neurological examination incomplete)
As soon as the LP is done, advance the clock just a few minutes and order the antibiotics. Your whole aim in meningitis should be to give the antibiotics as soon after the LP as possible. You do the head CT before an LP in some patients because of the possibility that the intracranial pressure is increased unevenly in the skull. Focal findings and papilledema indicate a possible mass lesion and an LP may lead to herniation. Meningitis increases intracranial pressure, but it is increased evenly throughout the brain and that is why herniation does not occur just from the elevated intracranial pressure of meningitis.
Orders:
Ceftriaxone, vancomycin, and dexamethasone IV
Droplet isolation
What class of medication does vancomycin belong to?
a. Glycopeptide
b. Penicillin
c. Aminoglycoside
d. Vancomycin
Answer a. Glycopeptide
Glycopeptides are glycosylated cyclic nonribosomal peptides. The glycopeptides are vancomycin, teicoplanin, and telavancin.
What is the mechanism of action of vancomycin?
a. Ribosomal
b. Cell wall
c. Protein synthesis
d. DNA gyrase
Answer b. Cell wall
Vancomycin inhibits the backbone polymers of the cell wall of gram-positive bacteria. Because gram-negative bacteria form through a different mechanism, vancomycin has no effect on gram-negative organisms. Macrolides (e.g., azithromycin) inhibit ribosomes. Quinolones inhibit DNA gyrase, which is the enzyme needed to unwind DNA so it can be replicated.
Vancomycin inhibits the cell wall through a different mechanism than do cephalosporins and penicillin.
Blood cultures were obtained and the LP performed. Move the clock forward to obtain results. Patients are placed on droplet isolation until you are sure the organism is not Neisseria meningitidis.
Report:
CSF: 2400 WBCs; 87% neutrophils
Protein: 89 mg/dL (elevated)
Gram Stain Characteristics of Organisms
• Positive diplococci: Pneumococcus
• Negative diplococci: Neisseria
• Positive cocci in clusters: Staphylococcus
• Pleomorphic gram-negative coccobacilli: Haemophilus
• Positive rod: Listeria
The Gram stain shows gram-positive diplococci.
What would you do differently based on this finding?
a. Stop ceftriaxone.
b. Stop vancomycin.
c. Stop droplet isolation.
d. Add penicillin.
e. Stop dexamethasone.
Answer c. Stop droplet isolation.
Droplet isolation is only needed for Neisseria meningitidis. You should not alter the antibiotics until the results of culture and sensitivity are known. If the organism is fully sensitive, a penicillin or cephalosporin is superior in efficacy to vancomycin. If the organism if penicillin resistant, vancomycin is needed.
Dexamethasone must be continued because it decreases both neurological injury from meningitis as well as mortality.
For which organism do steroids give the greatest mortality benefit?
a. Pneumococcus
b. Neisseria
c. Staphylococcus
d. Haemophilus
e. Listeria
Answer a. Pneumococcus
The reason for the benefit being greatest with pneumococcus is not clear. Steroids decrease inflammation in general.
Move the clock forward 6 to 12 hours and reexamine the patient. You know it is bacterial meningitis from the thousands of neutrophils on CSF as well as the Gram stain. Bacterial meningitis is profoundly damaging to the brain and it is important to be sure there is no neurological damage.
PE:
Neurological examination: nonfocal, more comfortable
HEENT: photophobia and neck stiffness still present
What is the most common neurological sequela from meningitis?
a. Memory loss
b. Hearing loss
c. Respiratory distress
d. Visual disturbances
Answer b. Hearing loss
The most common neurological effect of meningitis is hearing loss. Patients on initial presentation can have ocular problems such as double vision. Untreated meningitis can result in hydrocephalus. It is not clear why there is more damage to the eighth cranial nerve than the other parts of the system.
Which site of the brain is most involved in this patient?
a. Parenchyma
b. Arachnoid
c. Dura
d. Ventricles
Answer b. Arachnoid
The part of the brain most affected by meningitis is the leptomeninges or immediate covering of the brain. The arachnoid is under the dura and this is the main part affected. Encephalitis infects the brain parenchyma. None of these infections is in the ventricles.
Move the clock forward another 6 and then 12 hours. Once the patient is stable, you should look for a source of the meningitis.
Order:
Head CT/MRI
Chest x-ray
Sources of Pneumococcal Meningitis
• Sinusitis
• Mastoiditis
• Pneumonia
Why is intracranial pressure up in meningitis?
• Vasogenic edema
• Cytotoxins from neutrophils
• Inflammation of arachnoid villi
What is the mechanism of hydrocephalus developing as a complication of meningitis?
a. Inflamed arachnoid villi cannot drain CSF.
b. Granuloma forms.
c. Cells undergo coagulation necrosis.
d. Fibrinoid necrosis occurs.
Answer a. Inflamed arachnoid villi cannot drain CSF.
CSF normally drains out of arachnoid villi. When they are inflamed by infection or blocked by red blood cells, hydrocephalus can develop. This is the mechanism of developing hydrocephalus from subarachnoid hemorrhage.
On the second hospital day, you are called by the nurse because the patient has suddenly turned bright red. On examination his skin is red. Vancomycin is infusing.
What is the mechanism of this “red man syndrome?”
a. Allergy
b. Histamine release from mast cells
c. IgE
d. Neutrophil dysfunction
Answer b. Histamine release from mast cells
Vancomycin provokes a histamine release from mast cells when infused rapidly. The solution is to slow the rate of infusion.
On the following day, the CSF and blood cultures are reported as growing Streptococcus pneumonia that is sensitive to penicillin. A head CT shows no sinusitis and no mastoiditis.
Orders:
Stop vancomycin.
Continue ceftriaxone (or ampicillin).
Continue steroid.
Keep the patient in the hospital for at least 10 days of IV antibiotics.
Routine repeat LP is not needed.