Listeria Monocytogenes


Article Author:
Denver Rogalla


Article Editor:
Paul Bomar


Editors In Chief:
Dustin Constant
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
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Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
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Saad Nazir
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Navid Mahabadi
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John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
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Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
4/3/2019 3:09:07 PM

Introduction

Listeria monocytogenes is a gram-positive, facultative intracellular rod bacteria that is catalase positive and beta-hemolytic when grown on blood agar. There have been several historical foodborne illness breakouts involving L. monocytogenes. In 1981, L. monocytogenes was revealed to be a foodborne illness linked to a variety of foods.  In 1985, a massive outbreak of L. monocytogenes was traced to a brand of soft cheeses involving 142 cases, 28 deaths, and 20 fetal losses.[1] While L. monocytogenes is not the most common foodborne illness, it has the highest mortality rate secondary to its unique virulence factors.[2]

L. monocytogenes’ virulence factors include but are not limited to intracellular mobility via actin polymerization and the ability to replicate at refrigerator temperatures. This makes it difficult for food industries to control. Transmission of the bacteria occurs via the fecal-oral route and most commonly involves foods such as cold deli meats and unpasteurized dairy products. The number of cases involving L. monocytogenes has decreased in recent years thanks to advances in prevention, detection, and treatment.

Infection via L. monocytogenes (listeriosis) includes but is not limited to sepsis, meningitis, encephalitis, spontaneous abortion, or fever and self-limiting gastroenteritis in a healthy adult. Populations at the most risk for L. monocytogenes infection include pregnant females, infants, immunocompromised individuals, and elderly.

Etiology

Listeria commonly causes meningitis in the young (neonates), elderly, and immunocompromised patient population. Healthy individuals infected with L. monocytogenes typically have a self-limiting gastrointestinal infection with fever and diarrhea. The Listeria family consists of 10 different species with L. monocytogenes found most consistently in humans. L. monocytogenes has 13 different serotypes based on a variety of flagellar and surface antigens.  However, there are only three serotypes (1/2a, 1/2b, 4a) that inflict disease in humans.[3] In general, the infectious dose of L. monocytogenes is large, meaning one must ingest a large number to cause clinical infection, but as growth and division can continue at refrigerator temperatures, these levels can be reached despite typical food storage precautions. Host immune response also affects the infectious dose. Utilization of proton pump inhibitors or other stomach acid suppression modalities makes it easier for L. monocytogenes to pass through the stomach and invade enterocytes.

Epidemiology

According to the Center for Disease Control (CDC), approximately 1,600 people get listeriosis each year with approximately 260 people dying from the disease. The disease is most prevalent in pregnant women, infants, immunocompromised, and elderly (65 and older). Pregnant women are also at risk as they can acquire L. monocytogenes and pass it to their unborn fetus.

L. monocytogenes is ubiquitous as it can be found in soil, water, and decaying vegetation. The bacterium can also be found in the human digestive tract. Foods that have the highest rates of L. monocytogenes related infections include:

  • Raw sprouts
  • Unpasteurized milk
  • Soft cheeses
  • Cold deli meats
  • Cold hot dogs
  • Smoked seafood

Pathophysiology

Primary Virulence Factors

  • Internalins (InlA and InlB): Bacterial surface proteins for host cell attachment
  • Listeriolysin O (LLO): Helps the bacteria escape from host cell vacuole
  • Actin polymerization (ActA): Helps the bacteria move within and between cells
  • Phosphatidylinositol-specific phospholipase C (PI-PLC): Helps the bacteria escape host cell vacuole and cause membrane disruption

L. monocytogenes can grow at refrigerator temperatures.  Low temperatures induce enzymes such as RNA helicase which improves L. monocytogenes’ activity and replication at low temperatures. The ability to produce biofilms enhances L. monocytogenes ability to survive harsh environments. L. monocytogenes also utilizes flagella at lower temperatures. This mechanism enables the ability to propel itself and latch onto enterocytes early in infection, but eventually losing the flagella the longer the bacteria is exposed to higher temperatures.

L. monocytogenes has cell-surface galactose residues, lipoteichoic acids, and surface proteins called "internalins" (internalin A and B) that binds primarily to gastrointestinal epithelial cells via host protein cadherin, allowing entry into the cell. After invasion into host cells, the bacteria has a propensity to initiate a cell-mediated immune response in the host. Phagocytized L. monocytogenes can lyse the internalized vacuole via a pore-forming cytotoxic protein called "listeriolysin O," (LLO) among other phospholipase proteins which are not pore-forming.  LLO is also responsible for the beta-hemolysis seen when grown on blood agar. Once free of the vacuole, the bacteria can disrupt the normal cellular processes by moving through the cell via actin polymerization.  The bacterium surface protein, ActA, is stimulated by host intracellular proteins that innately regulate actin filaments. These actin monomers are connected asymmetrically (only at one end) utilizing host intracellular cytoskeleton filaments. This tail, often referred to as a rocket tail, gives the bacteria the ability to move swiftly through the intracellular cytosol, between cells, or disseminate hematogenously.

Cadherin is an epithelial attachment protein that is found in abundance in the blood-brain barrier as well as the placental-fetus barrier which may explain why the bacteria can infect neonates and cause meningitis. L. monocytogenes forms "rocket tails" via actin polymerization that allows the bacteria to move rapidly between cells, avoid antibody detection, and spread hematogenously.

Once the infection has occurred, L. monocytogenes can cause amnionitis, sepsis, spontaneous abortion in pregnant women, granulomatosis infantiseptica, and meningitis. Healthy individuals infected with L. monocytogenes typically have self-limiting gastroenteritis with diarrhea and vomiting.

History and Physical

Always consider treating for L. monocytogenes in the following patient populations:

  • Neonates (Usually younger than 29 days old)
  • Elderly
  • Immunocompromised
  • Pregnant women

Listeria meningitis presents with fever, neck stiffness, headache, altered mental status, neurological deficits, and other classic signs of meningitis. The patient may demonstrate a positive Brudzinski's or Kernig's sign on physical exam. The patient may have an altered mental status and may not be alert and oriented to their name, location, and date. Inquire about the use of stomach acid suppressors as they increase the risk of L. monocytogenes infection.

Pregnant women or otherwise healthy adults may present with general "flu-like" illness including fever, diarrhea, headache, chills, nausea, vomiting, myalgias. Although, some patients may be completely asymptomatic.

For additional history, ask about any food the patient has recently ingested, particularly milk, soft cheeses, and cold deli meats or hot dogs.

Evaluation

The diagnosis of L. monocytogenes requires a culture of the bacteria from the blood, cerebral spinal fluid, or placental fluid. Once in the lab, Listeria species grows on a special type of agar called Meuller-Hinton agar. Culture will reveal gram-positive rods with colonies that are beta-hemolytic.

According to the CDC, stool cultures are neither sensitive nor specific for diagnosing L. monocytogenes.

Treatment / Management

Preventing transmission of L. monocytogenes involves avoiding foods commonly contaminated with L. monocytogenes and proper hand-washing technique.

Initial presentation of the patient requires analysis of their hemodynamic status and resuscitating as needed.

If meningitis is suspected, consider doing the following:

  • Blood cultures
  • Lumbar puncture
  • Antibiotics
  • CT scan of the head, non-contrast

The antibiotic treatment of choice is intravenous (IV) ampicillin or penicillin G. An alternative treatment is trimethoprim-sulfamethoxazole if the patient has a penicillin allergy.[4] L. monocytogenes is inherently resistant to all cephalosporin antibiotics.

Since other causes of meningitis include gram-positive organisms such as Streptococcus pneumoniae and gram-negative organisms such as Neisseria meningitidis, Ceftriaxone is added as a treatment regimen. Gentamicin is utilized to mostly cover for gram-negative etiologies of meningitis such as Escherichia coli in the infant population. Finally, Vancomycin is added for Methicillin-resistant Staphylococcus aureus coverage.

For broad coverage of bacterial meningitis in populations susceptible to L. monocytogenes, consider the following regimens:

  • Less than one month old: Ampicillin plus gentamicin
  • Adults with depressed cellular immunity or older than 50 years old: Vancomycin plus ceftriaxone plus ampicillin

For prevention of L. monocytogenes in the general population, the FDA has also approved a variety of different food additives including bacteriophage (Listeria Phage P100) sprays. The spray contains a bacteriophage virus that can eliminate L. monocytogenes. The spray would be primarily utilized on deli meats and cheeses.[5]

Differential Diagnosis

Consider other infectious organisms that also cause meningitis including but not limited to herpes simplex virus, Neisseria meningitidis, and Streptococcus pneumoniae. A lumbar puncture can help distinguish between bacterial causes and viral causes. Bacterial causes of meningitis typically have a high polymorphonuclear leukocyte count.

Other causes of a headache and/or fever include but are not limited to:

  • Influenza Virus Infection
  • Strep Pharyngitis
  • Migraine headache
  • Tension headache
  • Cluster headache
  • Subarachnoid Hemorrhage
  • Acute otitis media
  • Subdural hematoma
  • Epidural hematoma
  • Mononucleosis
  • Intracranial mass/tumor

Prognosis

Studies have shown that L. monocytogenes is the third leading cause of death from food-borne illnesses in the United States, with approximately 260 deaths annually.[6] Mortality rates with confirmed L. monocytogenes infection are around 15% but can be higher depending on patient status and comorbidities.[6] Nearly 25% of pregnancy-related cases have poor outcomes including fetal demise.[8] Early recognition and treatment with ampicillin, penicillin G, or trimethoprim-sulfamethoxazole are very effective in treating L. monocytogenes.

Consultations

Infectious disease specialists should be consulted when managing patients with suspected meningitis or bacteremia secondary to L. monocytogenes infection.

Deterrence and Patient Education

If patient risk factors are present (pregnant, elderly, immunocompromised) patients should be cognizant of what foods they are ingesting. Be wary of the following foods: 

  • Raw sprouts
  • Unpasteurized milk
  • Soft cheeses
  • Cold deli meats
  • Cold hot dogs
  • Smoked seafood

Pearls and Other Issues

  • Always consider L. monocytogenes as an infectious agent in a patient that is a neonate, elderly, or immunocompromised.
  • Transmission involves the fecal-oral route. L. monocytogenes is a foodborne illness that can replicate at refrigerator temperatures.
  • Ampicillin or trimethoprim-sulfamethoxazole is the treatment of choice along with other broad-spectrum antibiotics until an infectious agent can be confirmed.
  • Early recognition is the key to an increased chance of survival.  
  • L. monocytogenes is uniformly resistant to cephalosporin antibiotics.

Enhancing Healthcare Team Outcomes

L. monocytogenes is a foodborne illness that has the propensity to cause meningitis or fetal demise in unborn infants. Primary care clinics and emergency departments are the first line of defense in diagnosing patients with meningitis and initiating appropriate therapy. Intake nurses and triage staff have an important role in recognizing unstable vital signs that might trigger systemic inflammatory response (SIRS) criteria and should alert the physician of these findings. Having a high suspicion for meningitis, performing diagnostic testing, and starting with broad-spectrum antibiotics in the emergency department to cover the most likely organisms based on patient risk factors. Early detection and diagnosis of meningitis are critical for good outcomes. If the patient is diagnosed with meningitis, this will require admission to the hospitalist team with consultation with an infectious disease physician to help narrow the spectrum of antibiotic coverage by analyzing cerebrospinal fluid and blood cultures. Infectious disease physicians and hospitalists should work closely with pharmacists to choose the correct antibiotics for the patient. After recovery and discharge, the patient should establish care or follow-up with their primary care physician. Finally, there should be hospital committees in place as well as protocols for treatment of L. monocytogenes associated infections.[6] (Level IV)

Outcomes

Currently, available data shows that the overall mortality of L. monocytogenes, when it progresses to meningitis or sepsis, is relatively high compared to other food-borne illnesses. The mortality percentage increases in patients that have more comorbidities.[7] A patient without coexisting disease has an approximately 10.7% mortality rate versus a patient with several comorbidities including diabetes and heart disease who has a mortality rate is near 24%.[6] Immunocompetence also plays a large role in overall mortality for patients.


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Listeria Monocytogenes - Questions

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Which of these organisms contains a molecule that resembles lipopolysaccharides?



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Which of the following bacteria can grow in the cold and need to be cultured in the cold?



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A 27-year-old female G1P0 15 weeks pregnant presents to the emergency department with chief complaint of neck stiffness and fever. Patient has not been feeling well for 3 days. Workup leads to meningitis caused by listeria monocytogenes. What food did she likely ingest over the last 3 days?



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A 79-year-old male presents to the emergency department with a chief complaint of headache and fever for four days. A lumbar puncture is performed, and cerebral spinal fluid cultures are obtained. Bacterial meningitis is confirmed. The bacterium responsible can translocate from cell to cell via actin polymerization. What do the gram stain results show for the bacterium?



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Which of these organisms contains a molecule that resembles lipopolysaccharide?



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A patient who is 8 weeks pregnant ate some unpasteurized cheese 2 days ago and now presents with muscle aches, diarrhea, low-grade fever, and malaise. She says the pregnancy has been uneventful, but she has persistent nausea all the time. Blood work and urinalysis are all normal. Examination of stools reveals a gram-positive organism with "tumbling motility." What is the most likely diagnosis?



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A 75-year-old male presents to the emergency department with fever, chills, headache, and neck stiffness. Meningitis is suspected, and a lumbar puncture is performed. What is the antibiotic of choice to cover for Listeria monocytogenes?



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A male with chronic lymphocytic leukemia is undergoing chemotherapy. Two weeks later, he presents with a headache, fever, and generalized malaise. He says he is not feeling well and has been having a stiff neck. Meningitis is suspected and CSF fluid is sampled. The fluid reveals diphtheroid-like gram-positive rods in CSF. What is the MOST likely organism present?



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Consumption of unpasteurized milk can lead to the acquisition of which of the following?



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What is the most likely cause of illness in a neonate who develops granulomatous lesions with microabscesses acquired through food-borne transmission from manure-contaminated cabbage, unpasteurized milk, and fresh Mexican-style cheeses?



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Which of the following antibiotics is effective against L. monocytogenes?



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A 71-year-old male with leukemia is undergoing chemotherapy. Two weeks later he presents with a headache, fever, and generalized malaise. He says he is not feeling well and has been having a stiff neck. Meningitis is suspected and CSF fluid is sampled. The fluid reveals diphtheroid-like Gram-positive rods in the CSF. What is the most likely organism?



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Which group would not receive empiric coverage for Listeria monocytogenes for presumed meningitis?



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Which organism is most commonly associated with unpasteurized milk consumption?



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A 70-year-old female presents to the emergency department with a chief complaint of fever and headache. She states that this has been sick for five days and he has never had anything like this before. She also complains of occasional blurry vision and neck stiffness. Lumbar puncture is performed, and cerebrospinal fluid analysis reveals gram-positive rods. What is a virulence factor for this organism?



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A mother brings in her 25-day old male son to the emergency department to be evaluated. She says that he has a fever of 102 F taken rectally over the last 6 hours. He is also very irritable and has not been eating or producing urine. He is breast fed. Besides cerebral spinal fluid analysis, what other lab tests can be utilized to confirm a Listeria monocytogenes infection?



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Listeria Monocytogenes - References

References

Choi MH,Park YJ,Kim M,Seo YH,Kim YA,Choi JY,Yong D,Jeong SH,Lee K, Increasing Incidence of Listeriosis and Infection-associated Clinical Outcomes. Annals of laboratory medicine. 2018 Mar     [PubMed]
Jordan K,McAuliffe O, Listeria monocytogenes in Foods. Advances in food and nutrition research. 2018     [PubMed]
Hunt K,Blanc M,Álvarez-Ordóñez A,Jordan K, Challenge Studies to Determine the Ability of Foods to Support the Growth of Listeria monocytogenes. Pathogens (Basel, Switzerland). 2018 Oct 5     [PubMed]
Komora N,Bruschi C,Ferreira V,Maciel C,Brandão TRS,Fernandes R,Saraiva JA,Castro SM,Teixeira P, The protective effect of food matrices on Listeria lytic bacteriophage P100 application towards high pressure processing. Food microbiology. 2018 Dec     [PubMed]
Temple ME,Nahata MC, Treatment of listeriosis. The Annals of pharmacotherapy. 2000 May     [PubMed]
Jackson KA,Gould LH,Hunter JC,Kucerova Z,Jackson B, Listeriosis Outbreaks Associated with Soft Cheeses, United States, 1998-2014{sup}1{/sup}. Emerging infectious diseases. 2018 Jun     [PubMed]
Ranjbar R,Halaji M, Epidemiology of Listeria monocytogenes prevalence in foods, animals and human origin from Iran: a systematic review and meta-analysis. BMC public health. 2018 Aug 23     [PubMed]

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