Infectious Disease · PANCE / PANRE

Listeriosis

Gram-positive rod causing febrile gastroenteritis in healthy hosts and invasive disease — meningoencephalitis, bacteremia, and stillbirth — in pregnancy, neonates, elderly, and immunocompromised.

Also known as: Listeria monocytogenes, Listeria meningitis, neonatal listeriosis, granulomatosis infantiseptica

Overview

Infection with Listeria monocytogenes, a facultative intracellular, gram-positive, catalase-positive, beta-hemolytic, tumbling-motile rod that crosses the placental, intestinal, and blood-brain barriers. Causes a benign febrile gastroenteritis in healthy adults but invasive disease in vulnerable hosts.

Epidemiology

Approximately 1,600 invasive cases per year in the US (CDC), with case-fatality near 20%. Outbreaks linked to deli meats, soft cheeses, raw milk, melons, and refrigerated ready-to-eat foods. Listeria uniquely grows at refrigeration temperatures.

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Question 1Infectious DiseaseMedium
A 68-year-old man with rheumatoid arthritis on a TNF inhibitor presents with 3 days of fever, headache, and progressive confusion. He recently ate deli meats and soft cheese at a family gathering. On exam, temperature is 38.9°C (102.0°F), he is lethargic, and he has new ataxia, diplopia, and a right-sided cranial nerve VI palsy. CSF shows 320 leukocytes/µL with neutrophil predominance, protein 110 mg/dL, glucose 42 mg/dL, and a negative Gram stain. MRI shows T2 hyperintensities in the brainstem. Which of the following is the most likely diagnosis?
  • APneumococcal meningitis
  • BHerpes simplex encephalitis
  • CListeria rhombencephalitis
  • DTuberculous meningitis
Reveal answer & full explanation
Correct answer: C — Listeria rhombencephalitis
  • APneumococcal meningitis
  • BHerpes simplex encephalitis
  • CListeria rhombencephalitis
  • DTuberculous meningitis

Why Listeria rhombencephalitis is correct

  • Brainstem involvement (ataxia, diplopia, cranial nerve VI palsy, and brainstem T2 hyperintensities on MRI) in a febrile adult is the distinctive rhombencephalitis pattern of Listeria monocytogenes.
  • Host risk factors align: age >65 and TNF-inhibitor use impair the Th1/IFN-γ cell-mediated immunity needed to clear this facultative intracellular organism, plus the classic deli-meat and soft-cheese exposure.
  • CSF here is neutrophilic with mildly elevated protein, low-normal glucose, and a negative Gram stain — typical of Listeria, whose low organism burden frequently yields a negative smear. Per IDSA, empiric meningitis coverage in patients >50, pregnant, or immunocompromised must add ampicillin to vancomycin plus ceftriaxone because cephalosporins are inactive against Listeria.

Why the others are wrong

  • Pneumococcal meningitis — the leading bacterial meningitis in older adults, but it causes diffuse cerebral disease, not focal brainstem rhombencephalitis, and the Gram stain is usually positive for gram-positive diplococci.
  • Herpes simplex encephalitis — favors the temporal lobes with a lymphocytic (mononuclear) CSF and normal glucose, not a neutrophilic CSF with brainstem lesions; diagnosed by HSV PCR.
  • Tuberculous meningitis — produces a subacute course with markedly low CSF glucose, lymphocytic pleocytosis, and basal meningeal enhancement, not an acute neutrophilic syndrome with isolated brainstem hyperintensities.
Question 2Infectious DiseaseMedium
A 29-year-old woman at 31 weeks' gestation presents with 3 days of fever, myalgias, and lower back pain after recently eating soft cheese and deli meats. She has no headache, neck stiffness, or diarrhea. Temperature is 38.7°C (101.7°F). Blood cultures grow a gram-positive, catalase-positive, tumbling-motile rod, and IV ampicillin is started. Which of the following complications is this infection most likely to cause?
  • AStillbirth and fetal loss
  • BHemolytic-uremic syndrome
  • CAscending flaccid paralysis
  • DPost-infectious arthritis
Reveal answer & full explanation
Correct answer: A — Stillbirth and fetal loss
  • AStillbirth and fetal loss
  • BHemolytic-uremic syndrome
  • CAscending flaccid paralysis
  • DPost-infectious arthritis

Why Stillbirth and fetal loss is correct

  • The vignette describes maternal listeriosis: a pregnant patient with flu-like illness, back pain, and deli meat/soft cheese exposure, with blood cultures growing the classic gram-positive, catalase-positive, tumbling-motile rod (Listeria monocytogenes).
  • Listeria crosses the placenta and establishes intra-amniotic and placental infection. In pregnancy the signature complications are fetal/neonatal: pregnancy loss, preterm labor, stillbirth, and neonatal sepsis (including granulomatosis infantiseptica).
  • The maternal illness is often mild relative to the fetal threat, which is why guidance is to draw blood cultures and treat suspected maternal listeriosis empirically with IV ampicillin to reduce fetal transmission and demise.

Why the others are wrong

  • Ascending flaccid paralysis — Guillain-Barre syndrome is a post-infectious complication of Campylobacter jejuni (and certain viral illnesses), not Listeria; Listeria's neurologic pattern is rhombencephalitis/meningoencephalitis in elderly or immunocompromised hosts, not a pregnant host.
  • Hemolytic-uremic syndrome — caused by Shiga toxin-producing E. coli O157:H7 and Shigella dysenteriae; it is not a complication of Listeria infection.
  • Post-infectious arthritis — reactive arthritis follows enteric (Shigella, Salmonella, Yersinia, Campylobacter) and genitourinary (Chlamydia) infections and is HLA-B27 associated; it is not a feature of listeriosis.
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Risk factors

  • Pregnancy (~17-fold increased risk; second/third trimester)
  • Neonates (early-onset and late-onset)
  • Age >65
  • Immunocompromise: solid organ transplant, hematologic malignancy, high-dose steroids, TNF inhibitors, HIV
  • Iron overload, hemochromatosis
  • Consumption of unpasteurized dairy, deli meats, soft cheeses, raw sprouts

Pathophysiology

Ingested bacteria cross the gut epithelium via internalin-E-cadherin interaction. Inside macrophages, listeriolysin O lyses the phagosome, allowing intracellular replication and actin-based ('comet tail') cell-to-cell spread. Tropism for the placenta and CNS drives the most feared complications. Cell-mediated immunity (Th1/IFN-γ) is required for clearance, explaining susceptibility in steroid and TNF-inhibitor users.

Clinical presentation

Symptoms

  • Healthy adults: self-limited febrile gastroenteritis 24 h after exposure
  • Pregnant: flu-like illness — fever, myalgias, back pain — frequently without GI symptoms
  • Invasive (elderly/immunocompromised): meningitis or meningoencephalitis with headache, fever, confusion, seizures, focal deficits
  • Neonatal early-onset (<7 days): sepsis, pneumonia, granulomatosis infantiseptica (disseminated microabscesses)
  • Neonatal late-onset (1-4 weeks): meningitis

Signs / physical exam

  • Meningismus less reliable in elderly and immunocompromised
  • Brainstem signs and rhombencephalitis — cranial nerve palsies, ataxia, altered mental status (a distinctive Listeria pattern)
  • Maternal fever near term; fetal distress on monitoring
  • Neonatal respiratory distress, hepatosplenomegaly, skin/throat granulomas

Classic findings

Rhombencephalitis (brainstem involvement) in a healthy or mildly immunocompromised adult is highly suggestive.

Differential diagnosis

  • Bacterial meningitis (pneumococcus, meningococcus, GBS, H. influenzae) — Younger and middle-aged adults; Listeria preferred over these in age >50, pregnancy, and immunocompromise
  • Viral meningoencephalitis (HSV, enterovirus) — Lymphocytic CSF predominance, normal glucose; HSV PCR and clinical course separate
  • TB meningitis — Subacute course, low CSF glucose, basal meningeal enhancement on MRI
  • Neonatal GBS sepsis — Early-onset GBS dominates in the first week; late-onset Listeria can mimic late-onset GBS
  • Chorioamnionitis from other causes — Maternal fever and uterine tenderness near term; consider Listeria if also flu-like illness or deli meat exposure

Diagnostic workup

Diagnostic criteria

Compatible clinical syndrome plus isolation of L. monocytogenes from a normally sterile site (blood, CSF, placenta, amniotic fluid).

Labs

  • Blood cultures — high yield in invasive disease
  • CSF: typically neutrophilic but may be mononuclear; mildly elevated protein, low-normal glucose
  • CSF Gram stain often negative (low organism burden); listeriolysin PCR or culture confirms
  • Stool culture not routinely diagnostic; selective media required
  • CBC, CMP, blood gas as clinically indicated

Imaging

  • MRI brain with contrast: rhombencephalitis with brainstem T2 hyperintensities, ring-enhancing abscesses; sensitive for posterior fossa involvement
  • Obstetric ultrasound and fetal monitoring in pregnancy

Treatment

First-line

  • Ampicillin-based therapy for listeriosis — IV ampicillin 2 g every 4 hours is the cornerstone
  • Add gentamicin for synergy in severe disease (meningitis, endocarditis, neonatal sepsis)
  • Trimethoprim-sulfamethoxazole IV for penicillin-allergic patients
  • Duration: 14-21 days for bacteremia; 21 days or longer for meningitis; 4-6 weeks for endocarditis or brain abscess

Pregnancy

  • IV ampicillin to reduce fetal transmission
  • Add gentamicin in severe maternal illness (use cautiously near delivery)
  • Avoid TMP-SMX in third trimester (kernicterus risk)

Neonatal listeriosis

  • Ampicillin + gentamicin
  • Treat 14 days for bacteremia, 21 days for meningitis

Immunocompromised meningoencephalitis

  • Add ampicillin to standard empiric meningitis regimen (vancomycin + ceftriaxone) when age >50, pregnant, or immunocompromised
  • Dexamethasone benefit unproven in Listeria — most guidelines do not recommend continuation if Listeria confirmed

Second-line / adjunct

  • Cephalosporins are INACTIVE against Listeria — empiric meningitis regimens must include ampicillin in at-risk groups
  • Linezolid or meropenem occasionally used in penicillin allergy with sulfa intolerance

Complications

  • Pregnancy loss, preterm labor, stillbirth, neonatal sepsis
  • Granulomatosis infantiseptica
  • Meningoencephalitis, brain abscess, rhombencephalitis
  • Endocarditis (rare)
  • Long-term neurologic sequelae in survivors

PANCE pearls

  • Add ampicillin to vancomycin + ceftriaxone for empiric meningitis in patients >50, pregnant, or immunocompromised.
  • Listeria grows at refrigerator temperatures — outbreak hallmark.
  • Pregnant patient with flu-like illness + deli meat exposure → think Listeria, draw blood cultures, treat empirically with IV ampicillin.
  • Cephalosporins are NOT active against Listeria.
  • Brainstem signs (cranial neuropathies, ataxia) in a febrile adult = rhombencephalitis pattern.

References

  • IDSA 2004 — IDSA Practice Guidelines for the Management of Bacterial Meningitis (Tunkel et al., Clin Infect Dis 2004)
  • CDC — CDC Listeriosis Surveillance and Outbreak Investigations
  • AAP Red Book — American Academy of Pediatrics Red Book — Listeria monocytogenes

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