Infectiology & Obstetrics & Neurology & Family Medicine
Listeriosis
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Listeriosis is a bacterial infection caused by Listeria monocytogenes, a facultative intracellular Gram-positive bacillus that is aero-anaerobic, psychrotrophic (able to multiply at refrigeration temperatures of 1-4°C) and resistant to high concentrations of NaCl. It is a reportable disease (MADO) in all Canadian provinces, including Quebec, due to its high mortality (20-30 % of invasive forms) and foodborne epidemic potential. Invasive listeriosis is a relatively rare disease - around 3-8 cases per 1 million people per year in Canada - but is disproportionately serious in vulnerable populations: pregnant women (risk × 10-20 times greater than the general population) + newborns + adults over 65 + immunocompromised people (HIV + transplant patients + chemotherapy + prolonged corticosteroid therapy + diabetes + cirrhosis). Contamination is almost exclusively foodborne - Listeria monocytogenes is ubiquitous in the environment (soil + plants + water) and can contaminate a wide variety of foods, especially ready-to-eat foods (deli meats + unpasteurized soft cheeses + smoked seafood + prepared salads + melons) → it resists refrigeration and can multiply slowly even in the fridge. Clinical forms are dominated by meningoencephalitis (the most fatal) and maternal-fetal listeriosis (responsible for late miscarriages + premature deliveries + rapidly evolving neonatal infections). Amoxicillin (or ampicillin) combined with gentamicin is the reference treatment - cephalosporins are ineffective against Listeria.
Microbiology, epidemiology and pathophysiology
- Microbiological characteristics of Listeria monocytogenes and virulence mechanisms : bacteriological characteristics : Gram-positive bacillus + short + non-spore-forming + motile (peritrichous flagella - characteristic «tumbling» motility at 20-25°C) → catalase positive + oxidase negative → hemolysis beta (listeriolysin O - LLO) on blood agar → growth at unusually wide temperatures temperatures (1-45°C) → optimum 37°C but growth possible at 1-4°C (psychrotrophic) → salt resistance (up to 10 % NaCl) → persistence in biofilms on food industry surfaces → clinically relevant serogroups : serogroup 1/2a (L1) + 1/2b (L2) + 4b (L4) → L. monocytogenes serogroup 4b is responsible for the majority of human foodborne epidemics + virulence mechanisms and intracellular pathogenesis : Listeria is a facultative intracellular pathogen → invasion of intestinal epithelial cells (via internalins InlA + InlB → bind to E-cadherin + Met) → survival in phagolysosomes → phagosome lysis by listeriolysin O (LLO) + phospholipases (PlcA + PlcB) → access to cell cytoplasm → actin polymerization (via ActA) → intracellular «comet-tail» propulsion «(rocket propulsion) → cell-to-cell passage without contact with the extracellular compartment → »Trojan horse" strategy → crossing biological barriers → intestinal epithelium → vascular endothelium → blood-brain barrier (BBB).encephalic barrier (BBB) → placenta → key cellular mechanisms : InlA → E-cadherin → signaling pathway → endocytosis → LLO (listeriolysin O) → pH-dependent → pore in phagolysosome membrane → release into cytoplasm → ActA → WASP → Arp2/3 → actin polymerization → intracellular mobility → transcellular passage → barrier crossing + epidemiological features: reservoir: environment (soil + water + plants + feces of many mammals and birds) → non-animal → almost exclusively dietary transmission (dietary in >99 % of cases) → direct human-to-human transmission: exceptional except mother → fetus (transplacental route)
- Epidemiology, risk foods and vulnerable populations: foods at major risk of contamination by Listeria monocytogenes : soft and semi-hard cheeseshard cheeses made from raw milk (Brie + Camembert + Roquefort + unpasteurized cheeses) + cured meats and processed meats (sausages + rillettes + pâtés + sliced ham + sausage meat) → contamination possible even after cooking (recontamination in the manufacturing chain) + smoked or cold-marinated fish and seafood (smoked salmon + smoked trout) + prepared salads and bagged products (raw vegetables + coleslaw + tabbouleh) + melons and cantaloupes (surface + knife) + soy sprouts + germinated seeds + ready-to-eat foodsin general → Listeria multiplies slowly but continuously in the fridge (1-4°C) → contaminated food can become dangerous after several weeks in the fridge; individual risk factors for invasive listeriosis : pregnancy : physiological immunosuppression (fetal immune tolerance → reduced cell-mediated immunity) → listeriosis risk × 10-20 times higher + fetus and newborn lack mature adaptive immunity → age >65 years: age-related impairment of cellular immunity → hematological malignancies + lymphomas + leukemias (impaired T immunity) + HIV (especially CD4 <100/µL) + organ transplantation + stem cell transplantation (immunosuppressive therapy) + prolonged corticosteroid therapy (≥1 mg/kg/d prednisone equivalent) + antiTNF (adalimumab + infliximab) + complement inhibitors (eculizumab) → these drugs increase the risk of listeriosis → liver cirrhosis + alcoholism + poorly balanced T2DM + CKD + pregnancy (see above) → healthy people with no risk factors : may develop non-invasive febrile gastroenteritis (most common form but often undiagnosed - stool + blood cultures not taken) → variable incubation: gastroenteritis: 6-48h → invasive listeriosis: 3-70 days (median 3 weeks)
Clinical forms, diagnosis and treatment
| Clinical form / appearance | Data, criteria and protocols | Key studies and recommendations |
|---|---|---|
| Clinical forms and diagnosis Meningitis meningoencephalitis - bacteremia - rhombencephalitis - maternal-fetal listeriosis - miscarriage - prematurity - newborn - gastroenteritis - CSF - blood cultures - stool culture - PCR |
Clinical forms of invasive listeriosis: bacteremia / septicemia: most frequent invasive form → high fever + chills + myalgias + headache + altered general condition → sometimes diarrhea and nausea preceding systemic signs → diagnosis: positive blood cultures for L. monocytogenes → mortality: 10-20 % → meningitis and meningoencephalitis: 2nd most frequent + most fatal form → meningeal syndrome (headache + stiff neck + phonophobia + photophobia) + fever + encephalitic signs (confusion + disorders of consciousness + convulsions + ataxia) → CSF : predominantly lymphocytic pleocytosis (or neutrophilic in the first few days) + high protein + normal or slightly low glucose → CSF gram: visualizes gram-positive bacillus in 30-40 % of cases → CSF culture + blood cultures + multiplex CSF PCR (BioFire FilmArray MEA) → L. monocytogenes detected + suggestive feature: picture of meningoencephalitis with abnormal movements (myoclonus + trismus) in an elderly or immunocompromised subject + listerial rhombencephalitis: selective brain stem involvement (bulb + bridge + cerebellum) → severe neurological picture: diplopia + ataxia + dysarthria + paralysis of cranial nerves (VI + VII + IX + X) + hemiplegia + respiratory disorders → brain MRI: T2 hypersignal of brainstem → difficult diagnosis (rare + atypical presentation) → high mortality (30-50 %) + severe sequelae + maternal-fetal listeriosis (pregnancy): pregnant women often present with a mild flu syndrome (fever + chills + myalgias + headache + low back pain) → WITHOUT meningitis (maternal cellular immunity is insufficient but sufficient to partially protect the maternal CNS) → but: L. monocytogenes crosses placenta → severe fetal infection → complications: late miscarriage (2nd-3rd trimester) + death in utero + prematurity + granulomatosis infantiseptica (severe neonatal form) → infected newborn: two forms: early (J0-J4 - contamination in utero): disseminated granulomas + skin rash + severe respiratory failure → mortality 25-50 % + late (J5-J28 - contamination during delivery): neonatal meningitis + mortality 15-25 % + diagnosis of listeriosis: blood cultures (gold standard): 2 sets of 2 vials ++ → positive in bacteremia and meningitis (75-90 % of meningitis) → 24-72h delay → CSF culture: specific → multiplex PCR on CSF (FilmArray MEA): result in 1h → sensitivity 90-98 % for L. monocytogenes + stool culture: possible if food epidemic → rarely positive in invasive listeriosis + serology: NOT available or useful for acute diagnosis | Swaminathan 2007 - Microbes and Infection: L. monocytogenes → virulence + pathogenesis + intracellular biology + Disson 2012 - PLoS Pathogens: barrier-crossing mechanisms → InlA + E-cadherin → Silk 2012 - Clinical Infectious Diseases: listeriosis in the USA → epidemiology + clinical forms + populations at risk + de Valk 2004 - European Journal of Epidemiology: listeriosis in Europe + epidemics + food + Charlier 2017 - Lancet Infectious Diseases (MONALISA cohort): invasive listeriosis + n=818 → clinical presentation + prognostic factors + mortality + PHAC + INSPQ Quebec: listeriosis + epidemiology + food epidemics + MSSS Quebec: MADO listeriosis → 24h mandatory declaration → investigation |
| Antibiotic treatment - amoxicillin and combinations Amoxicillin ampicillin - gentamicin synergy - ineffective cephalosporins - TMP-SMX - treatment duration - meningitis - pregnancy - immunocompromised - oral IV passage - resistance - co-amoxiclav |
Antibiotic treatment of listeriosis - basic principles: L. monocytogenes is naturally resistant to all cephalosporins (cefotaxime + ceftriaxone + etc.) → cephalosporins should NEVER be used as monotherapy to cover listeriosis → this is critical in community meningitis where co-coverage of Listeria is indicated in at-risk subjects → reference treatment - amoxicillin (or ampicillin) + gentamicin: amoxicillin IV: 2 g IV × 4-6/d + gentamicin: 5 mg/kg IV × 1/d (or 1.5-2 mg/kg × 3/d depending on protocols) → bactericidal synergy → gentamicin enhances amoxicillin's bactericidal activity against Listeria (bacteriostatic alone → bactericidal in combination with aminoglycosides) → duration of treatment : simple bacteremia in immunocompetent subjects: amoxicillin ± gentamicin × 14-21 days → meningitis + meningoencephalitis: amoxicillin IV × 21 days + gentamicin × 7-14 days → Potel 1991 + Cabellos 2012: minimum duration meningitis = 21 days → rhombencephalitis: 42 days or more → listeriosis in pregnancy: amoxicillin 2 g IV × 4/d + gentamicin IV × 7-14 days → or amoxicillin PO 3 g × 2/d if mild ambulatory form → no TMP-SMX in pregnancy (folate antagonist) → newborn: ampicillin 200 mg/kg/d IV + gentamicin × 14-21 days (meningitis → 21 days); alternative if penicillin allergy: trimethoprim-sulfamethoxazole (TMP-SMX - Septra DS): 10-20 mg/kg/d of TMP IV or PO × 14-21 days → good intracellular penetration → active against Listeria → reference alternative if allergic to beta-lactams + CONTRAINDICATION in pregnancy (1st trimester: teratogenic + 3rd trimester: neonatal hyperbilirubinemia) → meropenem : active against Listeria → usable if penicillin allergy + severe meningitis → DO NOT use chloramphenicol or vancomycin (Listeria is resistant or not very sensitive to them) + corticoids in Listeria meningitis: dexamethasone 0.15 mg/kg × 4/d × 4 days → debated → recommended for all presumed bacterial meningitis → but benefit on listeriosis specifically less clear → IDSA 2004 recommendations: dexamethasone for all bacterial meningitis + stop if Listeria confirmed (according to some experts) → other guidelines → maintain; co-amoxiclav (amoxicillin-clavulanate): NO interest - clavulanate adds nothing to amoxicillin for Listeria (no beta-lactamase in Listeria) | Charlier 2017 - Lancet Infectious Diseases (MONALISA n=818): invasive listeriosis → prognostic factors + treatment → amoxicillin + gentamicin → reference + van de Beek 2004 - NEJM: bacterial meningitis + dexamethasone → reduced sequelae + Tunkel 2004 - Clinical Infectious Diseases (IDSA meningitis guidelines): listeriosis + amoxicillin + TMP-SMX + duration + IDSA 2004: bacterial meningitis → dexamethasone + cephalosporins ineffective on Listeria → Hof 2003 - Lancet Infectious Diseases: listeriosis → treatment + amoxicillin + gentamicin + synergy + PHAC + INSPQ Québec: listeriosis → treatment + duration + INESSS Québec + RAMQ: amoxicillin IV + gentamicin + TMP-SMX → reimbursed in recognized indications + MSSS Québec: treatment of invasive listeriosis + protocols |
| Food prevention, pregnancy and public health Prohibited foods immunocompromised pregnancy - pasteurization - cooking - refrigeration - cleaning - food epidemic - product recall - MADO 24h declaration - INSPQ - epidemic investigation - traceability - amoxicillin prophylaxis exposure |
Listeriosis prevention - dietary recommendations for people at risk: at-risk populations who MUST follow strict recommendations: pregnant women + adults over 65 + immunocompromised (HIV + transplant patients + chemotherapy + anti-TNF + prolonged corticosteroids) → foods to be avoided absolutely: unpasteurized soft cheeses and pasteurized soft cheeses (brie + camembert + feta + bocconcini + bleu + roquefort + artisan cheeses) → replace with hard cheeses (cheddar + gouda + emmental + parmesan) + charcuterie and ready-to-eat products (rillettes + pâtés)eat (rillettes + pâtés + uncooked sausages + sliced ham at the counter) → heat to ≥74°C before consumption if necessary + uncooked or cold-smoked fish and seafood (smoked salmon + smoked trout + fish carpaccio) → replace with cooked products → cooked surimi and seafood = acceptable if eaten hot + bagged salads + delicatessen-prepared raw vegetables + sprouted seeds → rinse thoroughly + or cook + cut melons not eaten immediately (especially cantaloupes) → refrigerate immediately + eat within 24 hours → practical food prevention measures : fully cook all meats + poultry + seafood (internal T° ≥74°C) → separate raw from ready-to-eat foods → wash hands + surfaces + knives after contact with raw food → refrigerate at 4°C or below → do not eat food that has been refrigerated for more than 4 days (even if not expired) + Health Canada: official list of foods to avoid during pregnancy → update according to current product recalls; public health in Quebec and epidemic management: listeriosis = MADO in Quebec → mandatory declaration within 24 hours to the regional health inspector → INSPQ: epidemiological surveillance + molecular typing (whole genome sequencing - WGS) of strains → WGS enables cases to be linked to a common food source with high accuracy → epidemic investigation if ≥2 linked cases → identification of food source → product recall + market withdrawal → Canadian Food Inspection Agency (CFIA): responsible for food recalls → coordination with PHAC + INSPQ + MSSS + post-exposure prophylaxis (controversial): if pregnant woman exposed to contaminated food during a recognized epidemic → amoxicillin 3 g PO × 2/d × 7-10 days → or TMP-SMX 160/800 mg × 2/d × 7 days (excluding 1st and 3rd trimester) → limited data → individualized decision with infectiologist + obstetrician | Charlier 2017 - Lancet Infectious Diseases (MONALISA): listeriosis + pregnancy + prognostic factors + Pouillot 2012 - Risk Analysis: listeriosis risk according to foods + vulnerable populations + Health Canada: foods to avoid pregnancy + listeriosis → official list + CFIA (Canadian Food Inspection Agency): food recalls + listeriosis → history of Canadian epidemics → 2008 cheese epidemic (Maple Leaf deli meats) → 22 deaths in Canada + PHAC + INSPQ Quebec: listeriosis surveillance + WGS + epidemic investigations + MSSS Québec: MADO listeriosis → 24h declaration + Silk 2012 - Clinical Infectious Diseases: listeriosis USA + epidemiology + populations at risk + de Valk 2004 - European Journal of Epidemiology: listeriosis epidemics + traceability + INESSS Québec + food epidemic management protocols |
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Cephalosporins (cefotaxime, ceftriaxone) are ineffective against Listeria monocytogenes - any suspected bacterial meningitis in a patient at risk (age >65 + pregnant woman + immunocompromised) must include coverage with amoxicillin IV in addition to the cephalosporin: Listeriosis in pregnancy often manifests itself as a simple flu-like syndrome (fever + myalgias + low back pain) without meningitis - but it can lead to late miscarriage, death in utero or severe neonatal infection. Listeriosis is a MADO in Quebec - mandatory reporting within 24 hours. Pregnant women, the elderly and the immunocompromised should avoid soft cheeses, deli meats and smoked fish.
Situations requiring urgent hospitalization
Pregnant woman with fever ≥38°C + chills + low back pain + myalgias + uterine contractions or decreased fetal movements + after consumption of high-risk foods (soft cheese + deli meats + smoked salmon) → possible maternal-fetal listeriosis → urgent blood cultures × 2 + coprocultures + CBC + CRP + genital smear → amoxicillin 2 g IV × 4/d + gentamicin IV → fetal monitoring → obstetric consultation + infectiology → 24h MADO declaration → DO NOT wait for confirmation to treat.
Elderly + immunocompromised patient (lymphoma + corticoids + anti-TNF + HIV) with meningitis (fever + headache + stiff neck + confusion) + or rhombencephalitis (diplopia + ataxia + dysarthria + cranial nerve palsy) → CNS listeriosis → urgent lumbar puncture (if no signs of HTIC) + blood cultures + multiplex CSF PCR → amoxicillin 2 g IV × 6/d + gentamicin IV + dexamethasone 0.15 mg/kg × 4/d × 4 days → DO NOT treat with cefotaxime or ceftriaxone alone → urgent neuroimaging if rhombencephalitis suspected → 24h MADO declaration.
Newborn presenting in the first hours or days of life: respiratory distress + fever + poor feeding + rash + mother with fever during pregnancy → early neonatal listeriosis (granulomatosis infantiseptica) → neonatal emergency → blood cultures + LP + gastric fluid culture → ampicillin 200 mg/kg/d IV + gentamicin → neonatal intensive care.
Consult at Clinique Omicron
Les médecins de Clinique Omicron conseillent les femmes enceintes et les personnes immunodéprimées sur les mesures de prévention alimentaire (aliments à éviter + hygiène alimentaire), reconnaissent les signes de listériose invasive (syndrome grippal fébrile chez la femme enceinte + méningite chez l'immunodéprimé), prescrivent les hémocultures et orientent en urgence vers l'hospitalisation, assurent la déclaration MADO obligatoire dans les 24h, et participent à l'investigation des foyers épidémiques. Des consultations sont disponibles dans plusieurs points de service au Québec et en télémédecine. Pour prendre rendez-vous, Choose your online service.
The contents of this page are provided for information purposes only and do not replace the advice of a physician or infectious disease specialist. Listeriosis is a reportable disease (MADO) in Quebec with a 24-hour delay. Any bacterial meningitis in a patient at risk of listeriosis must include coverage with IV amoxicillin in addition to the standard cephalosporin.
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