Table of Contents
Definition / general | Essential features | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Laboratory | Case reports | Treatment | Clinical images | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Gross V, Totten AH, Garrett EM. Listeria monocytogenes. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/microbiologylmonocytogenes.html. Accessed December 23rd, 2024.
Definition / general
- Taxonomy: genus Listeria, family Listeriaceae
- Gram positive, facultative intracellular, facultative anaerobic, nonspore forming coccobacillus
- Known etiologic agent of food borne gastrointestinal disease (listeriosis), meningitis, pregnancy associated infections (neonatal sepsis, meningitis, rarely granulomatosis infantiseptica)
Essential features
- Environmentally ubiquitous in soil, water, in association with plants and as gastrointestinal (GI) flora for many animals
- Food borne disease associated with contaminated soft cheeses, unpasteurized dairy, luncheon meats / cold cuts, raw / undercooked poultry / meats, smoked fish and prepackaged vegetables / fruit
- Beta hemolytic, catalase positive, psychrophilic bacterium capable of tolerating adverse environmental concentrations
Epidemiology
- Contaminates an estimated 15 - 70% of raw milk, cheese, raw vegetables and deli meats
- Can transiently be found in stool of 3.5 - 5% of healthy adults
- Listeriosis incidence is estimated at 0.1 - 11.3 cases per million (varying data based on geographical location) (Microbes Infect 2007;9:1236)
- Highest incidence (16 - 27% of all cases) in pregnant women
- Elderly, infant and immunocompromised patients are also at risk for invasive infection
- U.S. rates of disease suggest that 1,600 illnesses, ~1,500 hospitalizations and ~260 deaths per year can be attributed to GI listeriosis (Emerg Infect Dis 2013;19:1)
- Most common during warmer months
- > 95% of attributed listeriosis cases are due to 3 serovars (1/2b and 4b within lineage 1 and 1/2a within lineage 2) out of 13 total (Clin Microbiol Rev 2023;36:e0006019)
Sites
- GI
- Invasive disease most commonly affects blood, CNS, placenta / genitourinary (GU)
- Invasive infection uncommonly presents as septic arthritis, intra-abdominal infection
- Rarely, cutaneous infection in individuals who handle animals
- References: Procop: Koneman's Color Atlas and Textbook of Diagnostic Microbiology, 7th Edition, 2016, Clin Microbiol Rev 2001;14:584
Pathophysiology
- Infection in adults occurs by ingestion of contaminated food
- Organism can grow at 4 °C, allowing proliferation under refrigerated conditions
- Infection in neonates may occur by transplacental spread or exposure to infected amniotic fluid
- Initial infection stage mediates translocation across intestinal mucosa, followed by lymphatic spread (liver and spleen) and then systemic infection at later infection stages (Clin Microbiol Rev 2001;14:584)
- PrfA virulence regulon proteins allow for invasion at sites of infection (enterocytes in GI tract, fibroblasts, hepatocytes, etc.)
- Facultative intracellular lifestyle facilitates immune evasion (Clin Microbiol Rev 2001;14:584)
- ActA promotes actin filamentation (actin tails), which mediate localized spread, avoiding extracellular immunologic defenses
- Listeriolysin O allows vacuolar escape and cytosolic replication
- Systemic vascular spread mediates CNS and placental invasion
Clinical features
- GI listeriosis
- Generally asymptomatic or mild
- GI upset, muscle aches, headaches, fever
- Incubation time of 2 - 67 days
- Invasive listeriosis
- Usually initiated with bacteremia, sepsis with potential for hematogenous spread to other sites, including CNS
- Meningitis, often subacute, indolent, with fever, headache, nuchal rigidity
- Severe cases due to encephalitis with neurological symptoms, such as seizures and altered mental status
- Pregnancy / neonatal listeriosis
- Infection often occurs during third trimester with mild flu-like symptoms in the mother
- Can cross transplacentally and cause intrauterine fetal death, spontaneous abortion, preterm labor
- Often causes severe disease in neonates, including febrile gastroenteritis, acute sepsis, pneumonia, meningitis, granulomatosis infantiseptica (nodular skin rash)
- Can be early onset (36 - 48 hours) or late onset (1 - 2+ weeks)
- References: Procop: Koneman's Color Atlas and Textbook of Diagnostic Microbiology, 7th Edition, 2016, Clin Microbiol Rev 2001;14:584
Diagnosis
- Diagnosis primarily by isolation in culture from sterile sites (i.e., blood, cerebrospinal fluid [CSF], amniotic fluid)
- Isolation from stool may represent colonization
- CSF Gram stain is only positive in 40% of cases (Carroll: Manual of Clinical Microbiology, 12th Edition, 2019)
- CSF chemistry may show normal glucose and elevated protein levels; polymorphonuclear leukocytes may be present
- Detected by BioFire FilmArray meningitis / encephalitis multiplex PCR panel (BioMèrieux)
- Nonclinical (industrial or public health microbiology) assays exist for molecular detection of L. monocytogenes (SureTect™ Listeria monocytogenes PCR Assay, 3M Molecular Detection Listeria assay) but are not covered further
Laboratory
- Culture
- Grows optimally on sheep blood agar at 35 - 37 °C with 5% CO2 atmosphere
- Listeria selective agars include LPM, Oxford and PALCAM
- Identification
- Gram stain: small, pleomorphic gram positive coccobacilli that may be confused for Streptococcus or other gram positive cocci
- If primary Gram stain has white blood cells, organisms will be found both intracellularly and extracellularly
- Colony morphology: small, shiny, white to gray colonies with a narrow zone of beta hemolysis
- Catalase test positive
- CAMP test positive (synergistic beta hemolysis with Staphylococcus aureus)
- Motile at 20 - 25 °C with umbrella sign pattern in agar, mostly nonmotile at 35 - 37 °C
- Bile esculin positive and lack H2S production on triple sugar iron agar
- Readily identified by MALDI TOF mass spectrometry
- Gram stain: small, pleomorphic gram positive coccobacilli that may be confused for Streptococcus or other gram positive cocci
- Listeriosis is a nationally reportable condition in the U.S.
- Centers for Disease Control and Prevention (CDC) investigates outbreaks and recalls contaminated foods
- Reference: Carroll: Manual of Clinical Microbiology, 12th Edition, 2019
Case reports
- 22 year old woman with type 1 diabetes mellitus and meningitis (Am J Case Rep 2022;23:e938024)
- 28 year old pregnant woman with chorioamnionitis and subsequent neonatal listeriosis (J Natl Med Assoc 2020;112:428)
- 53 year old woman with brain abscesses and systemic lupus erythematosus (Int J Rheum Dis 2021;24:1427)
- 67 year old immunocompromised woman with periprosthetic joint infection (JBJS Case Connect 2020;10:e19.00489)
Treatment
- Beta lactams and aminopenicillins (ampicillin or amoxicillin) are primary treatment modalities
- Cephalosporins (first - third generation) have limited to no clinical effectivity due to altered penicillin binding protein 3 (PBP3)
- TMP SMX (trimethoprim sulfamethoxazole) is an alternative treatment but is contraindicated in some stages of pregnancy
- Resistance rates are typically low (1 - 2%) but have been reported against tetracycline, ciprofloxacin and more sporadically, erythromycin, chloramphenicol and others (Antimicrob Agents Chemother 2010;54:2728, Clin Microbiol Rev 2023;36:e0006019)
Differential diagnosis
- Other causes of acute bacterial meningitis in adults:
- Streptococcus pneumoniae:
- Gram positive cocci in pairs or chains, often ovoid or lancet shaped; alpha hemolytic on blood agar
- Occurs most frequently in elderly patients and may be associated with pneumonia or bacteremia
- Streptococcus agalactiae (group B):
- Gram positive cocci in chains
- Neisseria meningitidis:
- Gram negative diplococci
- Meningitis may occur with bacteremia and sepsis; onset is often rapid
- Haemophilus influenzae:
- Gram negative coccobacilli
- Occurs most frequently in patients < 5 years old or > 65 years old and may be associated with pneumonia or bacteremia
- Streptococcus pneumoniae:
- Neonatal sepsis and meningitis:
- Streptococcus agalactiae (group B):
- Gram positive cocci in chains
- Escherichia coli or other enteric gram negative rods
- Staphylococcus aureus:
- Gram positive cocci in clusters
- Streptococcus agalactiae (group B):
Board review style question #1
A 31 year old woman experiences premature labor and delivers a baby boy at 30 weeks gestation. The neonate is lethargic and has signs concerning for meningitis. Gram stain of the amniotic fluid shows small, gram positive coccobacilli. Which of the following exposures is a notable risk factor for infection with this organism in pregnant women?
- Cat litter box
- Child with itchy, blister-like rash
- Red wine
- Soft cheese
Board review style answer #1
D. Soft cheese. The Gram stain indicates a bacterial pathogen consistent with Listeria monocytogenes. L. monocytogenes is usually transmitted by ingestion of contaminated foods such as raw vegetables, dairy products and meat. The organisms can cross the placenta and cause pregnancy complications, including premature labor, spontaneous abortion and intrauterine fetal death. In neonates, this infection commonly presents as sepsis and meningitis. Answer A is incorrect because exposure to cat feces is a risk factor for toxoplasmosis, which is a parasitic infection. Answer B is incorrect because exposure to varicella zoster virus (VZV), a common cause of blister-like rashes in children, can also result in pregnancy related complications but is not bacterial. Answer C is incorrect because red wine can cause congenital defects but is not associated with bacterial infection.
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Reference: Listeria monocytogenes
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Reference: Listeria monocytogenes
Board review style question #2
Which of the following routine laboratory culture and biochemical tests / traits are most informative for the identification of Listeria monocytogenes?
- CAMP test, catalase test and alpha hemolysis on sheep blood agar
- Catalase test, satellite test, Gram stain
- Gamma hemolysis on sheep blood agar, reverse CAMP test, motility agar
- Motility agar, beta hemolysis on sheep blood agar, catalase test
Board review style answer #2
D. Motility agar, beta hemolysis on sheep blood agar, catalase test. L. monocytogenes has beta hemolysis on sheep blood agar, is catalase positive from culture and also produces distinctive (umbrella sign) motility at 20 - 25 °C. Answer A is incorrect because the organism is not gamma or alpha hemolytic but is CAMP test positive. Answer C is incorrect because the reverse CAMP test is used for differentiation of Clostridium spp. Answer B is incorrect because testing for satellitism is used in the identification of Haemophilus spp.
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Reference: Listeria monocytogenes
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Reference: Listeria monocytogenes