Infectious Disease Compendium



Fever and headache. Unlike encephalitis, a mental status usually does not change until later in the disease. The sooner you do an LP and get antibiotics started the better (PubMed).

Who needs a CT before an LP for community-acquired meningitis? Immunocompromised, history of CNS disease, new seizure, altered mental status or focal neurologic exam (PubMed). Not that these guidelines are followed. 2/3 of the time a CT is ordered when none are needed, delaying the LP, wasting time and money and not altering management (PubMed). But. Not using impaired mental status and immunocompromised state before LP resulted in a prompt LP, earlier therapy and a better outcome (PubMed). So whose guideline should reign supreme?

Having a complication from an LP is quite rare and a CT is only moderately helpful for a contraindication (PubMed).

Viral cultures of CSF for aseptic meningitis in normal people are of extremely low yield; the PCR for enterovirus and herpes have a better yield (PubMed).

Lumbar puncture gives a hint as to the type of meningitis:

Aseptic: 100's of cells, normal glucose, normal to slightly elevated protein.

LP for Enterovirus, HSV, VZV ( PubMed)
  Enterovirus HSV VZV
WBC 51 240 207
Lymph% 91 100 100
Protein mg/L 640 1250 974
CSF/Blood glucose ratio .6 .48 .55
CRP 15 4.6 6.6

If you do not have > 10 WBC in the CSF, it is a waste of money to sent off viral PCRs (PubMed). But the smart way to do a spinal tap is to order the cell count, glucose and protein and then add on appropriate tests once you know what the pattern is, instead of the frequent approach of ordering everything like a microencephalopathic.

Viral meningitis can give a neutrophilic LP (PubMed): "45 (24.7%) had CSF neutrophilic pleocytosis. Enterovirus infections were the cause of 64% of neutrophil-predominant CSF and 33% of lymphocyte-predominant CSF, while herpes infections were the cause of 46% of lymphocytic pleocytosis and 20% of neutrophilic pleocytosis (p=0.003). Moreover, neutrophilic pleocytosis was seen more commonly in younger patients (p=0.001), patients with respiratory symptoms (p=0.04), and patients with higher CSF white cell counts (p=0.004)".

Pyogenic (bacterial): thousands of cells, mostly PMN's, low glucose, high protein. If 100's of PMN's and a protein of 500ish, think epidural abscess. It is rare, but early in bacterial meningitis, there can be a lack of WBC on the tap (PubMed).

Granulomatous (Tb/Fungal): hundreds of cells, mostly monocytes, low glucose, high protein. In TB meningitis the protein can be so high the CSF will clot, with a spider's web of red cells in it (PubMed) a rare but characteristic manifestation.

M. chimaera also cause a granulomatous encephalitis with widespread organ involvement (Pubmed).

An elevated CSF lactate is strongly indicative of pyogenic meningitis in one meta-analysis: "CSF lactate was a better marker for distinguishing bacterial meningitis from aseptic meningitis compared to other conventional markers including CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes...The cut-off value for CSF lactate concentration ranges from 2.1 to 4.44 mmol/L, (PubMed)." A lactate > 3.5 mmol/l is 100% sensitive for bacterial meningitis (PubMed).

The lactate is also valuable for post neurosurgical meningitis (Pubmed) with cutoff values ranging from 3.45 mmol/L to 5.4 mmol/L.

Although not an approved body fluid, galactomannan (Aspergillus) and 1-3 beta-D_ glucan (NOT made by Cryptococcus) are useful for the diagnosis of fungal meningitis (Pubmed).

A beta D glucan may be of use in rapid diagnosis of fungal meningitis, although somewhat insensitive (Pubmed).

There is pachymeningitis a “focal or diffuse thickening of dura mater visualized on MRI of the brain and/or histologic analysis of dura mater consistent with chronic inflammation.” Causes in this review were "... idiopathic pachymeningitis (n = 18; 30%); granulomatosis with polyangiitis (n = 13; 17%); Erdheim-Chester disease (n = 10; 17%); IgG4-related disease and tuberculosis (n = 3; 5% each); Rosai-Dofman disease, microscopic polyangiitis, and sarcoidosis (n = 2, 3% each); cryptococcal meningitis, Lyme disease, ear-nose-throat infection, postlumbar puncture, low spinal-fluid pressure syndrome, and lymphoma (n = 1 each)(Pubmed)."

There are a variety of non-culture methods to make a diagnosis, from PCR panels to metagenomic next-generation sequencing (aka magic. "Any sufficiently advanced technology is indistinguishable from magic." Clarke's First Law). If you have them, use them. The sooner you make a diagnosis, the sooner you can start appropriate therapy (Pubmed).

Traumatic tap? At least in kids "For every 1000 cell increase in CSF red blood cells per mm(3), CSF protein increases by 1.1 mg/dL (PubMed).

Epidemiologic Risks

Having a brain (Trump is intrinsically resistant). As always in ID where they have been, what they have been exposed to is the best way to find an odd etiology for the infection.

"...prior head or spine surgery is associated with increased Streptococcus pneumoniae meningitis outside of the postoperative period). Among the cases, only 33.3% had received any prior pneumococcal vaccinations (Pubmed).

"Patients with bacterial meningitis and diabetes mellitus are older, have more comorbidities, and higher mortality. S. pneumoniae and L. monocytogenes are the predominant pathogens, Listeria being more common...(Pubmed)."


Common etiologies

- Aseptic: common causes include enterovirus in summer/fall, herpes (during active genital outbreaks, especially the first outbreak. Patients never volunteer the information and docs never ask. A couple of times a year I get a call from the ER about someone with an aseptic meningitis. "Do they have active herpes?" I inquire. "Just a sec, I'll ask," they reply. More than a second passes. "Yeah, they got herpes. Never had it before." And the moral is, ask the patient with aseptic meningitis if the have genital ulcers. VZV (PubMed). West Nile virus, syphilis, HIV (acute illness), leptospirosis (which is a very common, but under-recognized, cause). NSAIDs, trimethoprim, and lamotrigine a few of the drugs that can cause an aseptic meningitis. Parvovirus.

Then there is LCM (Lymphocytic choriomeningitis virus), classically associated with hamster exposure. However, can occur in anyone with contact with the house mouse and around 10% of US citizens and US mice are seropositive (PubMed).

- Recurrent aseptic meningitis is usually due to Herpes 2 (Mollaret's) and if associated with eye/urethra symptoms, think of Bechets. And, for an off the wall cause, chronic strongyloidiasis with human T­-lymphotropic virus type 1 (PubMed).

- Pyogenic (bacterial)

In the US, all age causes are S. pneumoniae (58.0%), followed by Group B streptococci (18.1%), N. meningitidis (13.9%), H. influenzae (6.7%), and Listeria (3.4%) (PubMed).

Adults < 55: S. pneumoniae >> N. meningitidis.

It can be a direct extension from dental, sinus or ear infections. If otogenic in origin, surgery is more likely than radiology to find a bone defect (PubMed).

Age > 55: The same as < age 55 except 10% are due to gram-negative rods and they are at risk for Listeria (PubMed). The elderly will have a more indolent, less febrile presentation, often with only altered mental status, and how many of those get admitted a week (PubMed)?

In SE Asia the most common cause is S. suis, from pigs (PubMed, PubMed).

With community-acquired Enterobacteriaceae or culture-negative purulent meningitis think Strongiloides, at least in Japan (PubMed).

Molds (Review): Aspergillus, Fusarium, and Scedosporium, Mucor, and dematiaceous molds (Cladophialophora bantiana (also called Xylohypha bantiana), Rhinocladiella mackenziei, and Ochroconis gallopava (also called Dactylaria gallopava) and E. rostratum (with contaminated steroid injections).

Naegleria can mimic bacterial, the risk is swimming in warm freshwater, especially in the South, although another organism moving north with global warming. Rare and fatal (MMWR).

- Immunoincompetent: Listeria.

- a review of CNS infections in transplant infections here.

- Post Neurosurgical/nosocomial (PubMed): S. aureus (PubMed), S. epidermitis, Pseudomonas. If a shunt or drain in place, Propionibacterium acnes. Local flora will vary.

- Post spinal anesthesia, LP or similar procedure: oral Streptococci especially S. salivarius (PubMed). Some cases are due to the operator not wearing a mask (PubMed).

- Basilar skull fracture: S. pneumonia, H. influenzae, group A beta-hemolytic Streptococci.

- Granulomatous (Tb/Fungal): Cryptococcus, Coccidiomycosis, Histoplasmosis, Tuberculosis.

- Eosinophilic: due to Angiostrongylus, Coccidiomycosis, Gnathostoma (PubMed), Toxocara, Gnathostomiasis, and Baylisascariasis, Paragonimus westermani, and Paragonimus kellicotti in Missouri, Schistosoma japonicum, Taenia solium cysticerci, Coccidiomycosis, TB, syphilis. There are non-infectious causes as well: Cancer, Hodgkin’s disease, non-Hodgkin’s lymphoma, and eosinophilic leukemia. Medications: ciprofloxacin, ibuprofen, intraventricular vancomycin, gentamicin. Sarcoidosis.

The rare rupture of an epidermoid cyst; causes a chemical meningitis.

Empiric Therapy

- Viral: none needed. Everyone (or everyone who matters) will have meningitis with genital herpes, it does not need to be treated nor have there ever been studies to show treatment helps.

The best review to date suggests "Most patients with HSV meningitis rapidly improve, but immunocompromised hosts have more neurologic sequelae and may benefit from antiviral therapy. Our data suggest symptomatic treatment alone for immunocompetent patients with HSV meningitis, avoiding the cost and side effects of prolonged intravenous acyclovir therapy; in contrast, immunocompromised patients had improved outcomes and would, therefore, benefit from antiviral therapy (PubMed)."

Not the same as herpes encephalitis. THAT needs therapy.

- Bacterial: maximum dose vancomycin (perhaps dosed with a loading dose of 15 mg per kg then continuous infusion of 60 mg per kg per day after which resulted in good CSF levels despite the use of dexamethasone (PubMed). This is to cover penicillin intermediate/resistant S. pneumonia) PLUS a third-generation cephalosporin (usually cefotaxime or ceftriaxone ) PLUS dexamethasone 0.15 mg/kg every 6 h preferably 10-20 min prior to, or at the same time as the first antimicrobial dose, for 2-4 days.

Although as of Dec 2007, what to do (PubMed) is less certain as dexamethasone was not of benefit in adults in Sub Saharan Africa, most of whom were HIV positive and in Vietnam was associated with increased death in patients who subsequently found NOT to have bacterial meningitis (PubMed).

A review of steroids in 2013 suggests mostly benefit (PubMed),  including less hearing loss (Pubmed).

However, the use of dexamethasone 10 mg q 6 iv for four days lead to an absolute 10% decrease in mortality for pneumococcal meningitis (PubMed). For meningococcus, the best that can be said is that it doesn't increase harm and decreases the incidence of arthritis (Pubmed).

Dexamethasone should not be of use for Listeria (PubMed) and in one study INCREASED mortality (PubMed).

In children, glycerol (oral 85% glycerol for 48 h at a dosage of 1.5 g per kg every 6 h; the maximum volume was 25 mL per dose. The first dose was given 15 min prior to ceftriaxone) was superior to dexamethasone (PubMed). Or maybe not; one study suggests both glycerol and dexamethasone do nothing (PubMed).

Hypothermia increases mortality (PubMed).

A 2013 meta-analysis (PubMed) on osmotics in meningitis concludes "The only osmotic diuretic to have undergone randomized evaluation is glycerol. Data from trials to date have not demonstrated a benefit on death, but it may reduce deafness. Osmotic diuretics, including glycerol, should not be given to adults and children with bacterial meningitis unless as part of a carefully conducted randomized controlled trial." The last sentence the usual Cochrane cluelessness.

In the elderly or the immunoincompetent, add ampicillin to cover Listeria.

- Post neurosurgical/Trauma: vancomycin PLUS ceftazidime OR cefepime OR meropenem. Obviously, if a specific organism treat accordingly. If cultures are negative at three days it is usually safe to stop antibiotics (PubMed). One study suggests intraventricular gentamicin improves outcomes (PubMed).

- Granulomatous: treatment depends on the organism.

Intraventricular doses, adults (PubMed):

vancomycin 5–20 mg; gentamicin 4–8 mg; amikacin 30 mg; polymyxin B 5 mg; colistin 10 mg.


Recurrent S. pneumoniae, H. influenzae (PubMed) or other bacterial, think of CSF leak (PubMed).

Pituitary insufficiency may be not uncommon after meningitis (PubMed).

Alcoholics will be more ill, have more seizures, and a worse outcome (PubMed).

Hearing loss occurs in half of people with pneumococcal meningitis and is not suspected at discharge (PubMed).

If the patient is on anticoagulation, consider holding or reversing it as it increases the risk of hemorrhage and death (PubMed).

Curious Cases

Relevant links to my Medscape blog

Swimming in Body Fluids

Picky Picky

Meningitis and More

Not what I had hoped for.

Otitis Gone Bad

Meningitis and Lips

Say it, don't spray it

There and Back Again

Eventually Every Bug Show Up Everywhere

At the end of the day, safe >>> sorry.

Better than Expected

Not Positive


Calling the Zebra

A Relationship

Last Update: 06/30/20.