Listeria Monocytogenes Infection (Listeriosis)

Background

Listeria monocytogenes, which causes listeriosis, is an important pathogen in pregnant patients,^[1] neonates, elderly individuals, and immunocompromised individuals, although it is an uncommon cause of illness in the general population.^{[2, 3]}  Patients with cancer, particularly those of blood, also are at high risk for listeriosis.^[4]  

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Electron micrograph of an artificially colored Listeria bacterium in tissue.

It typically is a food-borne organism.^[5]  Listeria infection ranks as the third leading cause of mortality from foodborne illnesses in the United States, and there are 1,600 cases of Listeria infection and 260 fatalities due to the infection each year.^[3]

Listeria also is a common veterinary pathogen, being associated with abortion and encephalitis in sheep and cattle. It can be isolated from soil, water, and decaying vegetation. 

The most common clinical manifestation is diarrhea. A mild presentation of fever, nausea, vomiting, and diarrhea may resemble a gastrointestinal illness.^{[2, 6]}

The microorganism has gained recognition because of its association with epidemic gastroenteritis. In 1997, an outbreak of noninvasive gastroenteritis occurred in 2 schools in northern Italy, involving more than 1500 children and adults.^[7]

Bacteremia and meningitis are more serious manifestations of disease that can affect individuals at high risk. Unless recognized and treated, Listeria infections can result in significant morbidity and mortality.^[2]

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Pathophysiology

L monocytogenes is a motile, non–spore-forming, gram-positive bacillus that has aerobic and facultatively anaerobic characteristics. It grows best at neutral to slightly alkaline pH and is capable of growth at a wide range of temperatures, from 1-45°C.^{[2, 5]} It is beta-hemolytic and has a blue-green sheen on blood-free agar. It exhibits characteristic tumbling motility when viewed with light microscopy and is difficult to isolate in mixed cultures. It may be mistaken for streptococci or contaminants such as corynebacteria.

Most infections occur after oral ingestion, with access to the systemic circulation after intestinal penetration. Protection against Listeria is mediated via lymphokine activation of T cells on macrophages and by interleukin-18.

Healthy individuals may experience minor gastrointestinal symptoms when infected with Listeria. However, immunocompromised individuals are at risk for more severe infections, such as bacteraemia and meningitis, whereas pregnant people may experience miscarriage and stillbirth. Vulnerable populations, such as the elderly and pregnant women, have a mortality rate of 20-30% when infected with Listeria.^[5]

CNS infection may manifest as meningitis, meningoencephalitis, or abscess. Endocarditis is another possible presentation. Localized infection may manifest as septic arthritis, osteomyelitis, and, rarely, pneumonia.

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Epidemiology

The number of cases of Listeria infection is small, but the fatality rate is high.^[5]

Frequency

United States

The frequency of L monocytogenes infection is 2.9 cases per million population, with higher incidences in elderly individuals and pregnant women. It presents with higher incidence rates during the summer months.^[8] Pregnant women account for 27% of all cases, and most occur during the third trimester. Seventy percent of all nonperinatal infections occur in immunocompromised patients. Corticosteroid therapy is the most important predisposing association in patients who are not pregnant. Other risk factors include advanced age, recent chemotherapy, diabetes mellitus, end-stage renal disease, liver disease, and organ transplantation.^[9]

Nosocomial infection has been reported.

Listeria infection ranks as the third leading cause of mortality from foodborne illnesses in the United States. There are 1,600 cases of Listeria infection and 260 fatalities due to the infection in the United States each year.^[3]  

International 

Incidence rates range from 0.1 to 10 cases per 1 million individuals per year, varying across countries and regions globally.

Mortality/Morbidity

The overall mortality rate of L monocytogenes infection is 15-20%. Listeria accounts for 19% of all deaths due to food-borne infection.

Of all pregnancy-related cases, 22% resulted in fetal loss or neonatal death, but mothers usually survive.

Sex

With the exception of pregnant women, no sex predilection is recognized.

Age

Women of childbearing age commonly are affected.

Neonates and elderly individuals are at risk.

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History

L monocytogenes infection may be a self-limited gastrointestinal tract illness or a more severe CNS infection, bacteremia, or a localized infection such as monoarticular septic arthritis.

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Physical

Examination depends on the organ system involved.

Listeriosis in Pregnancy

Listeria may proliferate in the placenta and cause infection due to impaired cell-mediated immunity during pregnancy.

CNS infection is very rare during pregnancy, although it frequently is observed in other compromised hosts.

Fever, myalgias, arthralgias, back pain, and headache are classic symptoms of bacteremia. Symptoms may mimic those of a flulike illness. The infection may be mild and self-limited.

Listeriosis during pregnancy usually occurs during the third trimester, when cell-mediated immunity is at its lowest.

Preterm labor and/or delivery is common. Abortion, stillbirth, and intrauterine infection are possible.

Neonatal infection (granulomatosis infantisepticum)

Two forms are described.^[10]

Early-onset sepsis, with Listeria acquired in utero via transplacental transmission, results in premature birth. Listeria can be isolated in the placenta, blood, meconium, nose, ears, and throat, among other sites, and manifests as abscesses and/or granulomas.

Late-onset meningitis is acquired through vaginal transmission, although it also has been reported with cesarean deliveries.

CNS infection

Listeria has a predilection for the brain parenchyma, especially the brain stem, and the meninges.

Mental status changes are common.

Seizures, both focal and generalized, occur in at least 25% of patients.

Cranial nerve deficits may be present.

Strokelike syndromes with hemiplegia may occur.

Nuchal rigidity is less common.

Movement disorders may include tremor, myoclonus, and ataxia.

Patients may present with encephalitis, especially of the brainstem.^[11]

Meningitis is possible.

Ventriculitis, particularly of the fourth ventricle, may develop.

Cervical myelitis has been reported.^[12]

Brain abscess occurs in 10% of CNS infections, often located in the thalamus, pons, and medulla. This uncommon complication is associated with high mortality.^[13]

Febrile gastroenteritis

L monocytogenes can produce food-borne diarrheal disease, which typically is noninvasive.

The median incubation period is 1-2 days, with diarrhea lasting anywhere from 1-3 days.

The prevalence of diarrheal illness is high in individuals exposed to inocula of Listeria.

Immunocompetent patients present with self-limited fever, myalgias, and diarrhea and recover with supportive care.

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Causes

Most infections are due to food-borne transmission. It is more common in countries with industrialized food, storage, and distribution facilities.

A substantial minority of infections are transmitted by other modes. Transmission can occur transplacentally or via an infected birth canal. Isolated incidences of cross-infection in neonatal nurseries have been reported.

Nosocomial infection, although rare, has been reported.

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Laboratory Studies

Blood cultures should be performed. Blood culture results are positive in 60-75% of patients with CNS infections.

Listeria demonstrates "tumbling motility" in wet mounts of cerebrospinal fluid (CSF). Listeria organisms are motile in wet mounts of CSF.

CSF Gram stain results are positive in less than 50% of patients. CSF analysis reveals pleocytosis, and CSF protein levels are moderately elevated. CSF glucose levels may be low, and if so, are associated with a poor prognosis.

Laboratory results that show diphtheroids should prompt heightened awareness for the possibility of Listeria infection, particularly in immunocompromised patients.

CSF cultures are positive less frequently than blood cultures.

Rapid testing with monoclonal antibodies may detect the Listeria genus.

Serologic testing is not reliable.

Synovial fluid and/or prosthetic joint material should be cultured in cases of septic arthritis.

Stool cultures are neither sensitive nor specific.

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Imaging Studies

MRI is superior to CT scan for demonstrating CNS disease, especially in the brainstem.^[14]

Transesophageal echocardiography should be performed if endocarditis is suspected.

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Procedures

Lumbar puncture should be performed if CSF infection is suspected.

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Medical Care

Intravenous antibiotics must be started immediately when the diagnosis is suspected or confirmed.

Diagnosis is established by culture of the organism from blood, CSF, or other sterile body fluid.

Person-to-person transmission does not occur; therefore, isolation precautions are not necessary.

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Surgical Care

There have been case reports of L monocytogenes –associated bone and joint infections, but information is scarce. A 2012 retrospective study of 43 patients found that osteoarticular listeriosis primarily involves prosthetic joints and occurs in immunocompromised patients. In cases of periprosthetic joint infection, optimal therapy includes surgical removal of the prosthetic joint.^[15]

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Consultations

Listeriosis may be sporadic or may be part of a larger epidemic. The table below lists some of the most recent epidemics. Consultation with an infectious disease specialist or an epidemiologist is important when epidemic listeriosis is suspected.

Table. Epidemic Listeriosis

View Table

See Table

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Prevention

The following measures can be used to prevent listeriosis^[3] :

• Cook all raw food thoroughly.
• Wash raw vegetables.
• Avoid consumption of raw (unpasteurized) milk or milk products.
• Wash hands, knives, and cutting boards after handling uncooked foods.
• Pregnant or immunocompromised patients should avoid soft cheeses (eg, feta, Brie, Camembert, bleu). Cream cheese, yogurt, and cottage cheese are allowed.
• Reheat leftover or ready-to-eat foods (eg, hot dogs) until steaming hot.
• Avoid delicatessen foods unless they are thoroughly reheated.
• Cook food to a safe internal temperature.

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Medication Summary

Antibiotic therapy is the treatment of choice for invasive listeriosis. Bacteremia should be treated for 2 weeks if the patient is immunocompetent. Longer courses may be required in the immunocompromised patient. Meningitis should be treated for 3 weeks; endocarditis for 4-6 weeks; and brain abscess for at least 6 weeks. Ampicillin generally is considered the preferred agent, but other agents may be acceptable. Gentamicin frequently is added for synergy, but it may be discontinued after 1 week of clinical improvement in order to decrease the chance of renal toxicity or ototoxicity.^[17]

Glucocorticoids have not demonstrated benefit in Listeria meningitis.^[18]

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Ampicillin (Omnipen, Marcillin)

• Dosing, Interactions, etc.

Clinical Context:  Ampicillin is the drug of choice. It interferes with bacterial cell wall synthesis during active multiplication, causing bactericidal activity against susceptible organisms.

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Gentamicin

• Dosing, Interactions, etc.

Clinical Context:  Gentamicin is an adjunctive therapy that can be used in conjunction with ampicillin. It is an aminoglycoside antibiotic that interferes with bacterial protein synthesis by binding to the 30S and 50S ribosomal subunits. Dosing regimens are numerous and are adjusted based on creatinine clearance and changes in volume of distribution, as well as the body space into which the agent needs to distribute. Gentamicin may be given iIV/IM. Each regimen must be followed by at least a trough level drawn on the third or fourth dose, 0.5 hour before dosing; a peak level may be drawn 0.5 hour after a 30-minute infusion.

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Trimethoprim-sulfamethoxazole (Bactrim)

• Dosing, Interactions, etc.

Clinical Context:  This agent is indicated for patients unable to take penicillin antibiotics. It inhibits bacterial synthesis of dihydrofolic acid by competing with paraaminobenzoic acid, which results in inhibition of bacterial growth.

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Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

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