Infectiology & Obstetrics & Neurology & Family Medicine
Listeriosis
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
Clinique Omicron's physicians advise pregnant women and immunocompromised people on food prevention measures (foods to avoid + food hygiene), recognize the signs of invasive listeriosis (febrile flu syndrome in pregnant women + meningitis in immunocompromised people), prescribe blood cultures and refer urgent cases to hospital, ensure mandatory MADO reporting within 24 hours, and participate in the investigation of epidemic outbreaks. Consultations are available at several points of service in Quebec, and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
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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