View source for Listeria monocytogenes

==Background==
===Microbiology===

*Facultatively anaerobic, intracellular, non-sporulating, catalase [[Catalase::positive]], oxidase [[Oxidase::negative]], short, non-branching, [[Stain::Gram-positive]] [[Shape::bacillus]] that grows readily on blood agar, producing incomplete β-hemolysis
**Can be [[Stain::Gram-variable]] and [[Shape::pleomorphic]]
**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]] (especially third trimester), advanced [[HIV]], and [[Corticosteroids|corticosteroid]] immunosuppression, especially in transplant recipients
*In HIV and transplantation, may be prevented by ''[[Pneumocystis jirovecii|Pneumocystis]]'' prophylaxis
*Use of [[TNF-α inhibitors|anti-TNF-α 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 Infections===

*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===

*Infection in first and second trimester frequently result in intrauterine fetal death
*Later in pregnancy, stillbirth or spontaneous abortion is common
*Presents in prematurity or neonatal period as early-onset sepsis, likely acquired in utero during third trimester
**Disseminated listeriosis called '''granulomatosis infantiseptica'''
**Widespread abscesses and granulomas, especially in lungs, liver, and spleen
**Can have a miliary pattern on chest x-ray
**''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
*Mortality in neonatal infections is high at around 45%

===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]]