# CSF in Bacterial vs Viral vs Fungal Meningitis

> How do you distinguish bacterial from viral from fungal meningitis on CSF?

The CSF patterns that separate bacterial, viral, fungal and tuberculous meningitis, the exceptions that fool students, empiric regimens by age, and current prophylaxis and vaccine status.

Bacterial meningitis typically gives a neutrophil-predominant CSF of 1,000-5,000 cells/µL, raised protein and a CSF-to-serum glucose ratio of 0.4 or less. Viral meningitis gives a lymphocytic pleocytosis with normal glucose. Tuberculous and fungal meningitis give lymphocytes, raised protein and low glucose (low to normal in cryptococcal disease), and cryptococcal meningitis often adds a markedly raised opening pressure.

## How do you distinguish bacterial, viral and fungal meningitis on CSF?

Read every panel in the same order: opening pressure, white cell count and dominant cell, protein, then glucose as a ratio to a serum glucose drawn at the same time. More organism-level guides sit on the [Infectious Disease](/topics/infectious-disease) hub.

| CSF finding | Bacterial | Viral | Fungal (cryptococcal) | Tuberculous |
| --- | --- | --- | --- | --- |
| Opening pressure | Raised, typically 20-50 cm H₂O | Normal or slightly raised | Often very high; 25 cm H₂O or more in 60-80% with HIV | Can be raised if hydrocephalus develops; protein and glucose are better clues |
| White cells | Usually 1,000-5,000/µL | Usually under 1,000/µL | Variable; can be minimal in advanced HIV | Modestly raised |
| Dominant cell | Neutrophils, typically 80-95% | Lymphocytes; neutrophils may lead early | Lymphocytes | Lymphocytes |
| Protein | Raised in virtually all patients | Normal or mildly raised, usually under 200 mg/dL | Mildly raised | Often above 100 mg/dL |
| Glucose | Low; under 40 mg/dL in 50-60% | Normal | Low to normal | Low |
| CSF:serum glucose ratio | 0.4 or less (80% sensitive, 98% specific in children over 2 months) | Normal | Normal or low | Below 0.5 |
| Key test | Gram stain (positive in 60-90%), culture (70-85% before antibiotics) | Enterovirus, HSV and VZV PCR | Cryptococcal antigen; India ink positive in 60-80% | Acid-fast smear, culture (6-8 weeks), Xpert assay |
| Tempo | Acute; 3-6 hour antibiotic delays linked to higher mortality | Acute; mild cases resolve in 7-10 days | Subacute, building over weeks | Subacute; 1-3 week prodrome |

**Read glucose as a ratio.** The ratio is more reliable than the absolute value. In a prediction model IDSA cites, a CSF glucose below 34 mg/dL, a ratio below 0.23, protein above 220 mg/dL or more than 2,000 white cells/µL each pointed to bacterial rather than viral meningitis with at least 99% certainty. Lymphocytes with a low ratio suggest tuberculosis, fungi or *Listeria*. Term neonates run higher ratios, so 0.6 or less is abnormal at that age. On Gram stain, gram-positive diplococci suggest *S. pneumoniae*, gram-negative diplococci *N. meningitidis* and gram-positive rods *Listeria* (see the [gram-positive vs gram-negative guide](/blog/gram-positive-vs-gram-negative-bacteria-usmle)).

## Exceptions that break the CSF pattern

Examiners build stems around the cases that do not match the table.

- **Early or atypical bacterial disease:** in data cited by StatPearls, 12% of non-*Listeria* bacterial cases, and up to 23% of *Listeria* cases, lacked CSF findings suggestive of bacterial meningitis. Treat a toxic patient, not a reassuring number.
- **Pretreatment:** antibiotics before the tap lower culture yield and cut Gram stain yield by about 20%, but the cell count, glucose, protein and pre-antibiotic blood cultures usually still point to the diagnosis.
- **Early viral meningitis:** the first sample can be neutrophil-predominant, even after the first 24 hours, so the differential alone cannot exclude a virus.
- ***Listeria*:** the Gram stain is positive in only about 24% of cases (about 80% for other bacteria), the differential can be mononuclear, and glucose may be only mildly low.
- **HSV encephalitis:** lymphocytes and normal glucose, sometimes with red cells or xanthochromia from temporal lobe hemorrhage.
- **Cryptococcus in advanced HIV:** the cell count can be minimal or normal, so pressure and antigen make the diagnosis.

## Why bacterial meningitis produces this picture

Bacteria reach the meninges through the bloodstream, where *N. meningitidis* and *S. pneumoniae* readily cross the blood-brain barrier, by extension from otitis media or sinusitis, or through a dural defect such as a CSF leak. Lipopolysaccharide (gram-negative) and teichoic acid (gram-positive) activate microglia; the inflamed blood-brain barrier leaks plasma protein, neutrophils pour in, and cerebral edema raises intracranial pressure. IDSA calls this subarachnoid inflammation a major contributor to death and disability, the rationale for dexamethasone.

Bedside signs mislead. Only about 41% of patients with bacterial meningitis have the full triad of fever, neck stiffness and altered mental status, and absent Kernig or Brudzinski signs do not exclude meningitis. Petechiae or purpura suggest meningococcus, which can cause adrenal hemorrhage (Waterhouse-Friderichsen syndrome). *Listeria* can cause rhombencephalitis with ataxia and cranial nerve palsies, and tuberculous meningitis brings SIADH-related hyponatremia in 40-50% of patients.

## Organisms and empiric therapy by age and risk group

Age and immune status predict the organism, and empiric therapy covers every likely organism until cultures allow narrowing.

| Patient | Likely organisms | Regimen | Key point |
| --- | --- | --- | --- |
| Neonate (under 1 month) | Group B *Streptococcus*, *E. coli*, *Listeria* | Ampicillin plus gentamicin or cefotaxime; acyclovir if HSV is possible | No ceftriaxone with hyperbilirubinemia, prematurity or calcium-containing IV fluids |
| 1 month to 50 years | *S. pneumoniae*, *N. meningitidis*; group B *Streptococcus* in young infants; Hib if unvaccinated | Vancomycin plus ceftriaxone | Vancomycin covers resistant pneumococci until susceptibilities return |
| Over 50 years | *S. pneumoniae*, *N. meningitidis*, *Listeria*, group B *Streptococcus*, *H. influenzae* | Vancomycin plus ceftriaxone plus ampicillin | Cephalosporins miss *Listeria* |
| Impaired cell-mediated immunity | *Listeria*, *S. pneumoniae*, *Cryptococcus* | Vancomycin plus ceftriaxone plus ampicillin; send cryptococcal antigen | Steroids, transplant, advanced HIV |
| Neurosurgery, penetrating trauma, shunt or drain | Coagulase-negative staphylococci, *S. aureus*, *C. acnes*, gram-negative bacilli including *Pseudomonas* | Vancomycin plus cefepime, ceftazidime or meropenem | Remove the infected shunt (IDSA 2017) |
| Complement deficiency or inhibitor, asplenia, dormitories | *N. meningitidis*; pneumococcus and Hib with asplenia | Age-based regimen, then ceftriaxone or penicillin G | Also meningococcal vaccine indications |

*Listeria* is intrinsically resistant to cephalosporins; trimethoprim-sulfamethoxazole is the alternative in penicillin allergy, and treatment lasts at least 21 days. Late-onset neonatal meningitis (after 72 hours of life) shifts to vancomycin plus cefotaxime or cefepime, or vancomycin plus meropenem. Drug-by-drug coverage is in [antibiotic mechanisms and coverage](/blog/antibiotic-mechanisms-coverage-usmle).

## Dexamethasone: before or with the first dose, or not at all

IDSA recommends dexamethasone 0.15 mg/kg every 6 hours for 2-4 days in adults with suspected pneumococcal meningitis and in children with Hib meningitis, starting 10-20 minutes before or with the first antibiotic dose. In the European adult trial IDSA cites, deaths fell from 15% to 7% overall and from 34% to 14% with pneumococcus. Do not start it once antibiotics have been given, and continue it only if the Gram stain shows gram-positive diplococci or cultures grow *S. pneumoniae*. StatPearls reports no benefit in meningococcal meningitis, and it is not routine in neonates. Tuberculous meningitis is the reverse case, where corticosteroids are recommended.

## When to get a CT before the lumbar puncture

Image first only when a mass could make the tap dangerous: immunocompromise, known CNS disease, a seizure within the past week, papilledema, an abnormal level of consciousness or a focal deficit; the study behind the IDSA criteria also linked age 60 or older with an abnormal scan. Lateralizing signs like those in [stroke localization](/blog/stroke-localization-usmle) call for the scan. Antibiotics never wait for it: draw blood cultures, give dexamethasone and antibiotics, then scan, then tap.

## Cryptococcal meningitis: antigen, pressure and three phases

NIH guidance (updated October 2024, reviewed March 2026) pairs a high opening pressure with a variable lymphocytic pleocytosis, mildly raised protein and low-to-normal glucose. CSF antigen is usually positive and culture grows the yeast in 90-94%; early disease may show antigen only in serum, so test blood in any immunocompromised patient with an unexplained CNS illness.

- **Induction, 2 weeks:** liposomal amphotericin B 3-4 mg/kg daily plus flucytosine 25 mg/kg four times daily. Where resources are limited, WHO prefers one 10 mg/kg liposomal amphotericin dose with flucytosine and fluconazole 1,200 mg daily.
- **Consolidation, at least 8 weeks:** fluconazole 800 mg daily, cut to 400 mg once cultures are sterile and ART has begun.
- **Maintenance:** fluconazole 200 mg daily until at least 1 year after antifungal therapy began, stopped only once the patient is asymptomatic with a CD4 count of at least 100 and suppressed virus.

**Treat the pressure, not just the yeast.** With a pressure of 25 cm H₂O or more and symptoms, drain enough CSF to cut it by at least half or below 20 cm H₂O, repeating at least daily until symptoms improve and pressure normalizes; corticosteroids, mannitol and acetazolamide are not recommended. Watch amphotericin for nephrotoxicity, hypokalemia and hypomagnesemia, and flucytosine for cytopenias. Screening and ART timing are on the [CD4 count page](/blog/hiv-aids-cd4-count-usmle), and the organism is in the [Cryptococcus neoformans mnemonic](/blog/2026-05-23-mnemonic-to-remember-cryptococcus-neoformans).

## HSV encephalitis and viral meningitis

HSV encephalitis is the treatable emergency in the "viral" column, and HSV-1 causes about 90% of cases after the neonatal period. Expect fever, confusion, behavior change, seizures or aphasia, with temporal lobe changes on MRI. PCR is 96% sensitive and 99% specific, but repeat a negative test from the first 3 days when suspicion is high. Give IV acyclovir 10 mg/kg every 8 hours on suspicion, for 14-21 days, with hydration to protect the kidneys; mortality is up to 70% untreated and 20-30% treated.

Viral meningitis without encephalitis is usually benign. Non-polio enteroviruses lead in the US, viral meningitis peaks in summer and autumn in temperate climates, and HSV-2 is linked to recurrent meningitis. Most mild cases resolve in 7-10 days, and acyclovir's benefit is proven in HSV encephalitis, not meningitis. NSAIDs, sulfonamides, IVIG and monoclonal antibodies can cause drug-induced aseptic meningitis. The syndromes are compared in [viral meningitis vs encephalitis](/blog/2026-05-02-everything-you-need-to-know-about-viral-meningitis-encephalitis-for-step-1).

## Tuberculous, Lyme and syphilitic meningitis

Three slower-onset infections each need their own regimen.

- **Tuberculous:** lymphocytes, a glucose ratio below 0.5 and protein above 100 mg/dL, while smear and Xpert miss many cases. Give isoniazid, rifampin, pyrazinamide and ethambutol for 2 months, then isoniazid and rifampin for 7-10 months, plus dexamethasone or prednisolone tapered over 6-8 weeks (ATS/CDC/IDSA 2016); the 4-month regimens in the 2025 update exclude CNS disease. Mortality is 20-67% even with treatment.
- **Lyme:** meningitis, cranial neuropathy (classically facial palsy) or radiculoneuropathy; IV ceftriaxone, cefotaxime or penicillin G, or oral doxycycline, for 14-21 days (2020 guideline).
- **Neurosyphilis:** possible at any stage of syphilis; aqueous penicillin G 18-24 million units daily IV for 10-14 days (CDC 2021).

## Chemoprophylaxis for close contacts

Meningococcal close contacts are household members, child care contacts and anyone directly exposed to the patient's oral secretions, such as by kissing, mouth-to-mouth resuscitation or intubation, in the 7 days before onset, plus seatmates on flights longer than 8 hours. Give prophylaxis ideally within 24 hours of identifying the patient; more than 14 days after onset it has little or no value. Adult options are rifampin 600 mg every 12 hours for 4 doses, one 500 mg oral ciprofloxacin dose or one 250 mg IM ceftriaxone dose, each 90-95% effective against carriage. Since 2024, CDC has advised health departments to prefer rifampin, ceftriaxone or azithromycin over ciprofloxacin in a catchment area where, within a rolling 12 months, at least two cases, making up at least 20% of all reported cases, involve ciprofloxacin-resistant strains. Patients treated without a third-generation cephalosporin need carriage eradication too. For Hib, rifampin goes to all household contacts when the home includes an incompletely vaccinated child under 4 or an immunocompromised child under 18.

## Vaccines that prevent bacterial meningitis (status on 4 October 2026)

Hib, pneumococcal and meningococcal vaccines are the US mainstays, and invasive Hib disease has fallen by more than 99% since the prevaccine era. On 4 October 2026, CDC's posted child and adolescent schedule is still the version with an addendum updated July 2, 2025. A January 5, 2026 federal decision memo that moved routine meningococcal vaccination to shared clinical decision-making was stayed on March 16, 2026 by the federal district court in Massachusetts (American Academy of Pediatrics v. Kennedy). The government's appeal challenges only the part of that order covering ACIP appointments, not the stay of the memo, but check the live schedule before relying on any recommendation. As posted, PCV and Hib are infant series with a 12-15-month booster; MenACWY is given at 11-12 years with a booster at 16; MenB is a shared decision at 16-23 years, preferably 16-18; and MenABCWY (Penbraya, Penmenvy) can replace both when both are due at one visit. Both MenACWY and MenB are indicated for complement deficiency or complement inhibitors such as eculizumab and ravulizumab, asplenia including sickle cell disease, microbiologists and outbreaks; HIV, travel to hyperendemic areas, first-year college students in residence halls and military recruits are MenACWY-only indications.

> **10-second CSF read:** Neutrophils with a glucose ratio of 0.4 or less are bacterial until proven otherwise. Lymphocytes with normal glucose are viral, unless red cells and temporal lobe signs say HSV. Lymphocytes, low glucose and high protein over weeks mean tuberculous or fungal. Sky-high pressure with few cells in advanced HIV is cryptococcus until the antigen says otherwise.

## How USMLE tests it: classic stems and traps

Most stems pair one CSF panel with one host or exposure clue.

- **Jaundiced neonate with gram-positive cocci in chains:** group B *Streptococcus*; ampicillin plus gentamicin, not ceftriaxone.
- **Residence-hall student with petechiae and gram-negative diplococci:** *N. meningitidis*; ceftriaxone, and prophylaxis for close contacts within 24 hours.
- **70-year-old on prednisone with ataxia and a negative Gram stain:** *Listeria*; add ampicillin.
- **Weeks of headache, hyponatremia and a cranial nerve palsy, with high protein and low glucose:** tuberculous meningitis; four drugs plus steroids.
- **Child in August with lymphocytes and normal glucose:** enterovirus; supportive care.

The recurring traps are delaying antibiotics for the CT, giving dexamethasone after the first antibiotic dose, using vancomycin plus ceftriaxone alone in an older or immunosuppressed patient, excluding cryptococcus because the CSF is bland or the India ink is negative, treating cryptococcal pressure with acetazolamide, steroids or mannitol, and prescribing ciprofloxacin where CDC's resistance threshold has been met.

## Worked vignette: the headache that worsens after diagnosis

A 31-year-old man with untreated HIV (CD4 count 38/µL) has 3 weeks of headache and low-grade fever and now has blurred vision, without neck stiffness. Head CT shows no mass. Lumbar puncture: opening pressure 36 cm H₂O; 12 white cells/µL, 85% lymphocytes; protein 62 mg/dL; glucose 44 mg/dL with serum glucose 96 mg/dL; Gram stain and India ink negative. CSF cryptococcal antigen is positive, and liposomal amphotericin B plus flucytosine are started. The next morning his headache is worse. What is the most appropriate next step?

A. Acetazolamide
B. Intravenous dexamethasone
C. Repeat lumbar puncture to remove CSF
D. Mannitol
E. Start antiretroviral therapy today

**Answer: C.** Few cells, lymphocytes and a glucose ratio of about 0.46 argue against bacteria and fit cryptococcus at a CD4 count under 100; a negative India ink, positive in only 60-80%, does not exclude it. His pressure exceeds 25 cm H₂O with symptoms, so NIH guidance calls for therapeutic lumbar puncture that halves the pressure or brings it below 20 cm H₂O, repeated at least daily until he improves. Acetazolamide, corticosteroids and mannitol are not recommended for this pressure, and ART is usually deferred 4-6 weeks after antifungals begin because early ART increased mortality in a randomized trial.

## Sources

- IDSA: [bacterial meningitis (2004, now archived)](https://www.idsociety.org/practice-guideline/bacterial-meningitis/), [healthcare-associated ventriculitis and meningitis (2017)](https://www.idsociety.org/practice-guideline/healthcare-associated-ventriculitis-and-meningitis/), [Lyme disease (2020)](https://www.idsociety.org/practice-guideline/lyme-disease/), [drug-susceptible tuberculosis (2016)](https://www.idsociety.org/practice-guideline/treatment-of-drug-susceptible-tb/), [tuberculosis treatment update (2025)](https://www.idsociety.org/practice-guideline/treatment-of-drug-susceptible-tb/treatment-of-drug-resistant-and-drug-susceptible-tb-2025-update/)
- [NIH OI guidelines: cryptococcosis](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/cryptococcosis)
- StatPearls: [bacterial meningitis](https://www.ncbi.nlm.nih.gov/books/NBK470351/), [viral meningitis](https://www.ncbi.nlm.nih.gov/books/NBK545217/), [aseptic meningitis](https://www.ncbi.nlm.nih.gov/books/NBK557412/), [neonatal meningitis](https://www.ncbi.nlm.nih.gov/books/NBK532264/), [tuberculous meningitis](https://www.ncbi.nlm.nih.gov/books/NBK541015/), [HSV encephalitis](https://www.ncbi.nlm.nih.gov/books/NBK557643/), [listeriosis](https://www.ncbi.nlm.nih.gov/books/NBK534838/), [meningococcal disease](https://www.ncbi.nlm.nih.gov/books/NBK549849/), [amphotericin B](https://www.ncbi.nlm.nih.gov/books/NBK482327/)
- CDC: [bacterial meningitis](https://www.cdc.gov/meningitis/about/bacterial-meningitis.html), [viral meningitis](https://www.cdc.gov/meningitis/about/viral-meningitis.html), [Pink Book: meningococcal](https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-14-meningococcal-disease.html), [Pink Book: Hib](https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-8-haemophilus-influenzae.html), [meningococcal clinical guidance](https://www.cdc.gov/meningococcal/hcp/clinical-guidance/index.html), [ciprofloxacin resistance (MMWR 2024)](https://www.cdc.gov/mmwr/volumes/73/wr/mm7305a2.htm), [Hib chemoprophylaxis (MMWR 2014)](https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6301a1.htm), [meningococcal vaccines](https://www.cdc.gov/meningococcal/hcp/vaccine-recommendations/index.html), [meningococcal risk indications](https://www.cdc.gov/meningococcal/hcp/vaccine-recommendations/risk-indications.html), [child schedule](https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html), [schedule notes](https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-notes.html), [neurosyphilis (2021)](https://www.cdc.gov/std/treatment-guidelines/neurosyphilis.htm)

CSF panels become pattern recognition once you have worked through enough stems -- [Practice meningitis vignettes on StepGenie](https://dashboard.stepgenie.app/sign-up).

## Frequently asked questions

### What CSF glucose ratio suggests bacterial meningitis?

Compare CSF glucose with a serum glucose drawn at the same time. In the IDSA guideline, a CSF-to-serum ratio of 0.4 or less was 80% sensitive and 98% specific for bacterial meningitis in children older than 2 months, while an absolute CSF glucose below 40 mg/dL appears in only about 50 to 60% of bacterial cases. Term neonates normally run higher ratios, so 0.6 or less is abnormal at that age. Tuberculous and fungal meningitis can also lower the ratio.

### Can viral meningitis show neutrophils in the CSF?

Yes. Viral meningitis typically produces a lymphocytic pleocytosis, but an early sample can be neutrophil-predominant, and StatPearls notes that this is not limited to the first 24 hours, so the differential alone cannot separate viral from bacterial disease. Children tend to show more neutrophils than adults. A normal glucose ratio, protein under about 200 mg/dL, a negative Gram stain and a positive enterovirus or herpes simplex PCR support a viral cause.

### How do tuberculous and cryptococcal meningitis differ on CSF?

Both are subacute and lymphocytic. Tuberculous meningitis usually shows protein above 100 mg/dL and a CSF-to-serum glucose ratio below 0.5, often with cranial nerve palsies and hyponatremia, and acid-fast smear, culture and Xpert testing can all miss it. Cryptococcal meningitis in advanced HIV may show few cells, low-to-normal glucose and a very high opening pressure, 25 cm H2O or more in 60 to 80% of patients, and is confirmed by cryptococcal antigen.

### When should dexamethasone be given in bacterial meningitis?

Give dexamethasone 0.15 mg/kg every 6 hours for 2 to 4 days, starting 10 to 20 minutes before or together with the first antibiotic dose, for adults with suspected pneumococcal meningitis and children with Haemophilus influenzae type b meningitis. IDSA advises against starting it after antibiotics have been given, and against continuing it unless the Gram stain shows gram-positive diplococci or cultures grow Streptococcus pneumoniae. It is not routinely recommended in neonatal meningitis.

### Who needs antibiotics after exposure to meningococcal meningitis?

Close contacts need prophylaxis: household members, child care contacts and anyone directly exposed to the patient's oral secretions, for example through kissing, mouth-to-mouth resuscitation or intubation, in the 7 days before symptoms began, plus passengers seated next to the patient on flights longer than 8 hours. Give rifampin, ciprofloxacin or ceftriaxone, ideally within 24 hours. Where CDC's local threshold for ciprofloxacin-resistant strains has been met, CDC advises preferring rifampin, ceftriaxone or azithromycin.

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