Infectious Disease Compendium

Meningitis

Diagnosis

Fever and headache. Unlike encephalitis, mental status 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? Immunocompromise, 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).

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 type of meningitis:

Aseptic: 100 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 PCR's (PubMed). But the smart way to do a spinal tap is 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.

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).

A lactate > 3.5 mmol/l is 100% sensitive for bacterial meningitis (PubMed).

Granulomatous (Tb/Fungal): hundreds of cells, mostly monocytes, low glucose, high protein.

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)."

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 cryptococcus) are useful for the diagnosis of fungal meningitis (Pubmed).

Epidemiologic Risks

Having a brain (republicans are 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.

Microbiology

Common etiologies

- Aseptic: common causes include enterovirus in summer/fall, herpes (during active genital outbreaks, esp the first outbreak. Patients never volunteer the information and docs never ask. 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 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 and trimethoprim, and limotrigene are 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: same as < age 55 except 10% are gram negative rods and they are at risk for Listeria and gram negative rods (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).

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 fresh water, esp 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 esp 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, and Taenia solium cysticerci, coccidiomycosis, TB, syphilis, and Baylisascaris. 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.

Empiric Therapy

- Viral: none needed. Everyone (or everyone who matters) will have a 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 the increasingly 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).

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).

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 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 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.

Pearls

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

Pituitary insufficiency may be not uncommon after meningitis (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).

Rants