View source for Listeria monocytogenes

== Background ==
=== Microbiology ===
* Facultatively anaerobic, intracellular, non-sporulating, [[Catalase test::catalase-positive]], [[Oxidase test::oxidase-negative]], short, non-branching, [[Stain::Gram-positive]] [[Cellular shape::bacillus]] that grows readily on blood agar, producing incomplete β-hemolysis
** Can be [[Stain::Gram-variable]] and [[Cellular shape::pleiomorphic]]
** Can be initially misidentified as a diphtheroid
* 1 to 6 polar flagellae with '''tumbling motility''' at 25ºC
** Demonstrates "umbrella" motility in the tube
* Can grow at refrigerator temperatures, as low as 4ºC
* Doesn't grow on usual stool culture plates
* 13 serovars based on cellular O and flagellar H antigens
** Most disease from 4b, 1/2a, and 1/2b

=== Epidemiology ===
* In newborns, transmitted vertically from the mother
* In others, it is acquired from ingestion of contaminated food followed by mucosal invasion and bacteremia
* The bacterium can grow at fridge temperatures
* Both sporadic cases as well as foodborne outbreaks
** Largest outbreak in Canada was associated with deli meats in 2008
** Other outbreaks include ice cream (2015), frozen foods (2016), deli meat at a Druxy's in Princess Margaret Hospital (2018), prepackaged salads and kale (2018)
** Refer to the [http://www.inspection.gc.ca/about-the-cfia/newsroom/food-recall-warnings/eng/1299076382077/1299076493846 Canada Food Inspection Agency] for current recalls

=== Pathophysiology ===
* In gut, it is phagocytosed into endothelial cells, then disseminates hematogenously
** Endocytosis is aided by LPXTG on the mucosal cell surface and helps it to adhere, as well as E-cadherin, which activates phagocytosis
*** Some hypothesize that uptake of Listeria is increased by concurrent GI infections
** Listeriolysin O, the major virulence factor, is a pore-forming toxin that prevents T-cell response
** Listeriolysin O and phspholipases help is escape the phagosome
** Once in the cytoplasm, they activate actin to carry them to the cell membrane, where they push out and form filopods which can be phagocytosed by nearby cells
** Moves from cell to cell without time spent outside
* In the CNS, it can invade the blood-brain barrier endothelial cells directly, or it can be transported across by cirtculating white blood cells (&quot;Trojan horse&quot; mechanism), or it can be inoculated into oral tissues followed by macrophage phagocytosis and invasion of cranial nerves
** The latter may be most important for rhomboencephalitis
* Immune response primarily cell-mediated rather than antibody-mediated, since the bacterium doesn't spend any time outside of cells

=== Risk Factors ===
* Mostly around impaired cellular immunity
* Lymphoma, pregnancy, AIDS, and corticosteroid immunosuppression, especially in transplant recipients
* In AIDS and transplantation, may be prevented by ''Pneumocystis'' prophylaxis
* Use of anti-TNF-alpha medications
* Antacids that lower stomach acidity

== Clinical Manifestations ==

* Incubation period for invasive disease is [[Usual incubation period::30 days]] (range [[Incubation period range::11 to 90 days]])

=== Bacteremia ===
* Most common presentation outside of neonatal period is as a non-specific febrile illness
* Can cause non-specific febrile illness, often with a prodrome of diarrhea and nausea, myalgias

=== Febrile gastroenteritis ===
* Diarrhea, nausea, and vomiting, often with fever
* Associated with foodborne outbreaks, including chocolate milk, cold corn and tuna salad, cold smoked trout, deli meat
* Non-invasive in healthy patients
* Needs high innoculum

=== CNS infection ===
* Causes a spectrum of CNS disease from meningitis to encephalitis to rhombencephalitis to abscesses

==== Meningitis ====
* A bacterial meningitis with high mortality, usually in very young, old &gt;50 years, pregnant, or immunocompromised
** Malignancy is the most common risk factor, followed by transplantation, alcohol use disorder, immunosuppression, diabetes, and HIV
* Symptoms include subacute presention of fevers, nausea, and headache, with meningismus, and altered and fluctuating mental status
* Focal neurologic deficits
* Can sometimes have movement disorders, including ataxia, termors, and myoclonus, as well as seizures
* Two thirds have neutrophil-predominant CSF
* Mortality 15-30%
* Even if cured, can be left with permanent focal neurologic deficits

==== Encephalitis/Cerebritis ====
* Localized parenchymal infection that can lead to abscess formation
* Altered consciousness and cognitive dysfunction
* CSF cultures only positive about half the time
* Can mimic herpes encephalitis

==== Rhombencephalitis ====
* Brainstem encephalitis
* Can occur in health adults
* Diphasic illness, with prodrome of fever, headache, nausea, and vomiting lasting 4 days, followed by asymmetric cranial nerve deficits, cerebellar dysfunction, and focal neurological deficits
* Half of patients have respiratory failure
* CSF often only mildly abnormal

==== Brain abscess ====
* Often bacteremic and concurrent meningitis
* Can have abscesses in unusual locations, including subcortical abscesses of the thalamus, pons, and medulla

=== Spinal cord infection ===
* Rare cases

=== Endocarditis ===
* Can affect both native and prosthetic valves
* Mortality 50%

=== Neonatal listeriosis ===
* Stillbirth or spontaneous abortion is common, related to disseminated listeriosis called granulomatosis infantiseptica
** Widespread abscesses and granulomas, especially in liver and spleen
** ''Listeria'' can be isolated from meconium
* Can also present in prematurity as early-onset sepsis, probably acquired in utero
** ''Listeria'' can be isolated from conjunctiva, ear, nose, throat, meconium, amniotic fluid, placenta, blood, and sometimes CSF
* Can also present in term births as late-onset meningitis (~2 weeks post-partum)
** Probably acquired during delivery, since it is far less common with cesarean section

=== Other sites of infection ===
* Conjunctivitis, skin infection, and lymphadenitis
* Hepatitis, liver abscesses, cholecystitis, perintonitis, splenic abscesses, pleural and pulmonary infections, septic arthritis, osteomyelitis, necrotizing fasciitis, pericarditis, myocarditits, arteritis, and endophthalmitis

== Diagnosis ==
* Can be directly seen in blood or CSF, and cultured
** Grows on blood agar with incomplete beta-hemolysis
** Can also do cold-enrichment, incubating the plates at 4 to 10 ºC
** Growth may be inhibited by usual stool culture plates
* Serology to listeriolysin O can be helpful in non-invasive disease
* PCR is possible for CSF and tissue, detecting the ''hly'' gene that encodes listeriolysin O
* MRI can diagnose abscess (vs meningitis)

== Management ==
* Good supportive care
* It has intrinsic resistance to cephalosporins
* [[Ampicillin]] 2 g IV q4h is standard
** Delayed bactericidal activity
* [[TMP-SMX]] 5/25 mg/kg IV q8h is second-line
* If severe, can combine [[ampicillin]] and [[TMP-SMX]]
** Lower failure rate with fewer neurological sequelae than amp/gent
* [[Vancomycin]] and [[meropenem]] can be considered third-line
* [[Daptomycin]] and [[linezolid]] have in vitro activity
* Duration
** Bacteremia: 2 weeks
** CNS involvement: 3 weeks
** Rhomboencephalitis or abscess: at least 6 weeks with serial imaging
** Endocarditis: 4 to 6 weeks

== Prevention ==
* Follow good food preparation practices

=== General Recommendations ===
==== Washing and Handling Food ====
* Rinse raw produce under tap-water, including produce you later peel
* Scrub firm produce with a clean brush
* Dry it with a clean cloth

==== Clean and Safe Kitchen ====
* Wash everything
* Make sure your freezer freezes
* Clean fridge spills quickly

==== Cook Meat Well ====
* Cook it to safe internal temperature
* Use pre-packaged stuff as quickly as possible
* Use leftovers within 3 to 4 days

=== Safer Foods ===
* No unpasteurized milk or milk products

=== Higher-risk Persons ===
==== Meats ====
* No hot dogs, deli meats, fermented or dry sausages, unless they are cooked to 165ºF before serving
* Avoid getting hot dog juice or other meat juice on things
* Don't eat pate or meat spreads that aren't canned, and refridgerate after opening

==== Cheeses ====
* Only eat soft cheeses if they are made with pasteurized milk

==== Seafood ====
* No refrigerated smoked seafood unless it is cooked or canned
* Canned seafood is safe

==== Melons ====
* Wash hands after handling the melon
* Scrub the melon clean and drug it well, sanitizing the brush between uses
* Don't keep cut pieces for longer than 7 days
* Don't leave out for longer than 4 hours

{{DISPLAYTITLE:''Listeria monocytogenes''}}
[[Category:Gram-positive bacilli]]