CNS Infection of Listeria Monocytogenes

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Listeria monocytogenes

The only strain of Listeria that infects humans Aerobic and facultatively anaerobic Motile, beta hemolytic, non-spore-forming Gram-positive rod, regular, short Occurs singly or in short chains

Common presenting syndromes

Bacteremia and sepsis Chorioamnionitis CNS listeriosis (meningitis, meningoencephalitis, cerebritis, brainstem encephalitis, and brain or spinal abscess) Endocarditis Focal infections Recurrent spontaneous abortion granulomatosis infantisepticum Stillbirth

Epidemiology

Usually food-borne transmission 1% ~ 5% asymptomatic intestinal carrier High risk:

Neonates Elderly and pregnant women

Epidemiology

Additional predisposing factor:

Malignancy Transplantation (especially renal transplantation) Corticosteroid therapy HIV/AIDS DM Autoimmune disorder Splenomegaly Alcoholism Hemochromatosis

Listeria meningoencephalitis

Most often occurs in:

Neonates after three days Immunocompromised and elderly adults

Most common cause of bacterial meningitis in:

Underlying neoplastic disease, especially lymphoma Organ transplant recipients Receiving corticosteroids

Listeria meningoencephalitis

Clinical manifestation

Fever (92%) Altered sensorium (65%) Headache (46%) GI symptoms (22%) Focal neurologic findings (18%) Seizure (5%) Photophobia (3%)

42% lack meningeal signs on admission Seizure more common in Listeria than other bacterial meningitis

Listeria cerebritis

Results from direct hematogenous invasion of cerebral parenchyma The syndromes of meningitis and cerebritis can occur in the same patient Clinical presentation:
Ranges from fever and headache to hemiplegia Focal neurologic symptoms present in 87% of patients

Listeria brainstem encephalitis

Clinical manifestation (A biphasic course)

Headache, fever, nausea and vomiting Cranial nerve palsies, ataxia, tremor, other cerebellar signs, decreased consciousness, and possibly seizures and hemiparesis

Almost one-half develop respiratory failure The mortality is high

Diagnosis

D/D with
Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis in adults. Cryptococcus neoformans should also be considered in immunocompromised individuals.

Diagnosis is based on isolation of Listeria from a normally sterile site, usually blood, amniotic fluid, or cerebrospinal fluid
CSF culture (+) in 61% Blood culture (+) in 41%

Diagnosis

Imaging studies are negative in cases of CNS listeriosis without parenchymal CNS involvement In cases of parenchymal CNS involvement, MRI (imaging study of choice) and CT reveal areas of uptake without ring enhancement, involving the brainstem, cerebellum, and cerebral cortex MRI: T1WI Enhencing lesions T2WI High signal

Diagnosis

Gram stain of CSF is negative in 2/3 of cases of meningitis/meningoencephalitis (SEN 0~40%) Gram stain of CSF may be misleading in many of the remaining cases (usually misinterpreted as gram(+) diplococci, Diphtheroids) CSF examination
Lymphocyte >25% Elevated protein Reduced sugar poor prognosis

Treatment

For severe infections:

Ampicillin (200 mg/kg/d i.v. divided in six doses) or Penicillin (300,000 mg/kg/d i.v. divided in six doses) Combined with gentamicin (12 mg/kg every 8 hours, adjusted with renal function and followed by levels)

Penicillin-allergic patients:

Trimethoprim-sulfamethoxazole (20 mg/kg per day of the Trimethoprim component IV in four divided doses)

Combination of ampicillin and trimethoprimsulfamethoxazole might be more effective

Treatment

Other choices:
Imipenem and meropenem have excellent in vitro activity against Listeria Vancomycin is an alternative, but failures have been reported Erythromycin and Tetracyclines have in vitro activity against Listeria, but not recommended

Cephalosporins are inactive in vitro and ineffective clinically

Duration of Therapy

The optimal duration of antibiotic therapy is unknown Two weeks may be sufficient for bacteremia in immunocompetent patients At least six to eight weeks for CNS listeriosis in immunocompromised patients The response to therapy is monitored by cultures of blood and or CSF Treatment is continued until the CSF culture is negative and repeat MRI of the brain is normal The patients are then monitored for relapse

Prognosis

Early diagnosis and initiation of appropriate therapy are important 100% mortality rate in untreated patients The mortality rate of meningoencephalitis is among the highest among all causes of bacterial meningitis (13~43%) Mortality is higher among immunocompromised patients and those who develop seizures The mortality rate of cerebritis, CNS abscess, and endocarditis due to Listeria is even higher (~50%) 61% of survivors in each group had persistent neurologic sequelae

Summary

Most CNS listeriosis occurs in noenates, elderly and immunocompromised adults Early diagnosis and initiation of appropriate therapy are important First choice of drugs: Ampicillin or Penicillin plus Gentamicin The mortality rate of CNS listeriosis is high Neurologic sequelae are common among the survivors

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