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Author: Karen B Weinstein, MD, FACP, Clinical Assistant Professor, Department of Internal Medicine, Loyola University; Assistant Attending, Department of Internal Medicine, Rush Medical College; Associate Program Director, West Suburban Medical Center

Karen B Weinstein is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Illinois State Medical Society

Coauthor(s): Joanna Ortiz, MD, Infectious Disease Attending Physician, Clinical Instructor, Department of Internal Medicine, West Suburban Medical Center

Editors: Mark Raymond Wallace, MD, Infectious Disease Fellowship Director, Orlando Regional Healthcare; Clinical Professor of Medicine, Florida State University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Author and Editor Disclosure

Synonyms and related keywords: Listeria monocytogenes, L monocytogenes, diarrhea, listeriosis, epidemic gastroenteritis, bacteremia, meningitis, CNS infection, meningoencephalitis, endocarditis, septic arthritis, osteomyelitis, pneumonia, corticosteroid therapy



Background

Listeria monocytogenes, although an uncommon cause of illness in the general population, is an important pathogen in pregnant patients, neonates, elderly individuals, and immunocompromised individuals. It is typically a food-borne organism. Listeria is also 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.1 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.2

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.

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. 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.

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.

Frequency

United States

The frequency of L monocytogenes infection is 9.7 cases per million population. Annually, 2500 cases are reported, with higher incidence rates during the summer months.3 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.

Mortality/Morbidity

  • The overall mortality rate of L monocytogenes infection is 20-30%.
  • 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 are commonly affected.
  • Neonates and elderly individuals are at risk.



History

Disease may be a self-limited gastrointestinal tract illness or a more severe CNS infection or bacteremia.

Physical

Examination depends on the organ system involved.

  • Infection in pregnancy4, 5
    • 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 is observed frequently 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.4
    • 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 infection6
    • 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.7
    • Meningitis is possible.
    • Ventriculitis, particularly of the fourth ventricle, may develop.
    • Cervical myelitis has been reported.8
    • Brain abscess occurs in 10% of CNS infections, often located in the thalamus, pons, and medulla. This uncommon complication is associated with high mortality.9
  • Febrile gastroenteritis1
    • L monocytogenes can produce food-borne diarrheal disease, which is typically 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.
    • Patients present with fever, myalgias, and diarrhea and recover with supportive care.

Causes

  • Most infections are due to food-borne transmission.
  • 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.



Cryptosporidiosis
Gastroenteritis, Bacterial
Gastroenteritis, Viral
Meningitis
Sarcoidosis
Streptococcus Group B Infections
Toxoplasmosis
Wegener Granulomatosis

Other Problems to be Considered

Meningeal carcinomatosis
Lymphomatous meningitis
Multiple sclerosis
Vasculitis
Viral encephalitis or meningitis
Fungal meningitis
Brain abscess
Bacterial meningitis
Septic abortion
Pyelonephritis in pregnancy



Lab 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 culture findings are positive in nearly 100% of patients.
  • Serologic testing is not reliable.
  • Stool cultures are neither sensitive nor specific.

Imaging Studies

  • MRI is superior to CT scan for demonstrating CNS disease, especially in the brainstem.10
  • Transesophageal echocardiography should be performed if endocarditis is suspected.

Procedures

  • Lumbar puncture should be performed if CSF infection is suspected.



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.

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.

Epidemic Listeriosis

Year

Location

Source

2007
Massachusetts
Milk
2003
United Kingdom
Sandwiches
200211
United States (nationwide)
Delicatessen turkey breast
August 1998 to January 1999
Multiple states in the United States
Hot dogs, deli meats
19972Italy
Corn
199712Sweden
Rainbow trout
199513
Switzerland
Soft cheese
199414Illinois
Chocolate milk
199215France
Rillettes (pork product)
198516California
Mexican-style soft cheese
198317New England
Unpasteurized milk
198118Canada
Coleslaw



Antibiotic therapy is the treatment of choice. 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 is generally considered the preferred agent, but other agents may be acceptable. Gentamicin is added frequently for synergy, but it may be discontinued after 1 week of clinical improvement in order to decrease the chance of renal toxicity or ototoxicity.19

Drug Category: Antibiotics

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

Drug NameAmpicillin (Omnipen, Marcillin)
DescriptionDOC. Interferes with bacterial cell wall synthesis during active multiplication, causing bactericidal activity against susceptible organisms.
Adult Dose2 g IV q4h
Pediatric Dose200-400 mg/kg/d IV divided q4h
ContraindicationsDocumented hypersensitivity (also to other penicillins)
InteractionsProbenecid and disulfiram decrease renal excretion of ampicillin, causing an increase in levels; conversely, allopurinol increases excretion and has an additive effect on ampicillin rash; may decrease effect of oral contraceptives
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsDose adjustments may be necessary in renal failure; appearance of rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction

Drug NameTrimethoprim-sulfamethoxazole (Bactrim)
DescriptionIndicated for patients unable to take penicillin antibiotics. Inhibits bacterial synthesis of dihydrofolic acid by competing with paraaminobenzoic acid, which results in inhibition of bacterial growth.
Adult Dose20 mg/kg/d of trimethoprim IV divided q6h
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; megaloblastic anemia due to folate deficiency; infants <2 mo
InteractionsMay increase prothrombin time of warfarin, monitor coagulation tests and adjust dose prn; serum levels of dapsone and TMP may increase when administered concomitantly; incidence of thrombocytopenia purpura may increase when used concurrently with diuretics in elderly patients; hepatic clearance of phenytoin may be decreased and half-life prolonged when administered concurrently; sulfonamides can displace methotrexate (MTX) from plasma protein-binding sites, thus increasing free MTX concentrations; this may potentiate MTX effects in bone marrow depression; hypoglycemic response of sulfonylureas may be increased with concurrent administration of both medications; may decrease renal clearance of zidovudine, causing an increase in zidovudine levels
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsDiscontinue at first appearance of skin rash or sign of adverse reaction; obtain CBCs CBC count frequently; if significant reduction of any formed blood element is noted, discontinue therapy; goiter production, diuresis, and hypoglycemia may occur; high IV doses or prolonged infusions may cause bone marrow depression manifested as thrombocytopenia, leukopenia, or megaloblastic anemia
Exercise caution in patients with possible folate deficiency (eg, chronic alcoholism, elderly, anticonvulsant therapy, malabsorption syndrome)
Hemolysis may occur in G-6-PD deficiency; if signs of bone marrow depression occur, give leucovorin prn to restore normal hematopoiesis; oral leucovorin (5-15 mg/d) has been recommended; because of their unique immune dysfunction, patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment; administer adequate fluid to prevent crystalluria and stone formation; perform urinalyses and renal function tests during therapy

Drug NameChloramphenicol (Chloromycetin)
DescriptionBinds to 50 S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Adult Dose50-100 mg/kg/d PO/IV divided q6h for 10 d; not to exceed 4 g/d
Pediatric Dose50-75 mg/kg/d PO/IV divided q6h
ContraindicationsDocumented hypersensitivity
InteractionsAdministered concurrently with barbiturates, levels may decrease while barbiturate levels may increase, causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsUse only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (eg, aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)



Deterrence/Prevention

  • 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.



Medical/Legal Pitfalls

  • US regulatory agencies recommend a recall when L monocytogenes is detected in processed foods that are eaten without cooking.
    • The United States Department of Agriculture's Food Safety and Inspection Service has issued new regulations for ready-to-eat meat and poultry processing plants by outlining a program to control and test for L monocytogenes.11
    • Systems have not been perfected; therefore, patient education is most effective in prevention.



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Listeria Monocytogenes excerpt

Article Last Updated: Jun 23, 2008