Listeriosis Prevention & Treatment (PDF)

Listeriosis Listeria monocytogenes • Gram-positive rod, non-spore forming, nonbranching, aerobic. • Catalase positive • Grows well at refrigerator temperature (4 – 10 oC) : Cold enrichment • May look like diphtheroids, cocci, diploccocci. • Tropism for nervous system • Facultative intracellular or...

Listeriosis Listeria monocytogenes • Gram-positive rod, non-spore forming, nonbranching, aerobic. • Catalase positive • Grows well at refrigerator temperature (4 – 10 oC) : Cold enrichment • May look like diphtheroids, cocci, diploccocci. • Tropism for nervous system • Facultative intracellular organism Listeria monocytogenes • Grows well on Blood Agar, narrow zone of hemolysis . • Characteristic motility: • ‘Tumbling motility’:end - over- end at room temp.(25oC) • Umbrella motility seen in stab cultures of semisolid agar. • Biochemical tests to confirm id: Glucose, VP & Esculin positive Listeria monocytogenes on SBA Umbrella motility of Listeria in semisolid agar Listeria selective agar Listeria Epidemiology • Important zoonoses. • Of the seven Listeria species, only L. monocytogenes affects humans • Common in soil, decaying vegetation, fecal flora of many mammals (including 15% of healthy adults) • Foods: raw vegetables, raw milk, fish, poultry, meats, esp. deli meats (15-70%) Listeria hysteria Several reported food borne Listeria outbreaks: • Coleslaw, milk, soft cheeses (Brie,camembert,blue vein) • Deli ready meats, especially chicken, had highest rates of contamination • CDC study: – 11% of all refrigerator food samples were contaminated – 32% of sporadic cases can be attributed to soft cheeses or deli meats – 64% of pts had at least one contaminated food Populations at risk Impaired cell-mediated immunity: • Infants < 1 mo old (10% of patients) • Pregnant women (30% of patients; 60% of cases between 10-40 years old) • Adults > 60 years old • Hematologic malignancy patients • HIV patients • Organ transplantation recipients • Corticosteroid therapy recipients Listeria epidemiology • Human-to-human infection not documented except in: – Vertical transmission mother to fetus – Cross-contamination in delivery room – Nosocomial infection in newborn nursery • Contaminated mineral oil • Most cases foodborne Listeria mechanism of pathogenesis Ingestion of Listeria from food Intestine Mean incubation period: 31 days L. monocytogenes crosses mucosal barrier bloodstream Hematogenous dissemination Brain, placenta and other sites Listeria virulence factors • Internalin: allows attachment to host epithelial cells • Listeriolysin O: enables listeriae to escape from host cell phagosome • Act A: allows recruitment of host cell actin filaments • Siderophores: allow scavaging of iron from transferrin Listeria mechanism of pathogenesis • Listeria’s surface protein “internalin” interacts with Ecadherin, a receptor on epithelial cells. • Phagocytosis induced. Listeria mechanism of pathogenesis • Listeriolysin O lyses the phagolysosomal membrane. • Bacterium escapes into cytoplasm and avoids intracellular killing. Listeria mechanism of pathogenesis • In cytoplasm, bacteria divides. • Doubling time ~ 1 hr Listeria mechanism of pathogenesis • Listeria uses virulence factor Act A to induce host cell actin polymerization. • Actin filaments propel the bacteria to the host cell membrane. • Listeria has successfully hijacked the contractile system of the host cell for cell to cell migration. Listeria mechanism of pathogenesis • Bacteria push against cell membrane to form “filopods”. • Filopods are ingested by adjacent cells. Listeria mechanism of pathogenesis • The life cycle begins again in the new cell. • Listeria has moved from cell to cell without being exposed to antibodies, complement, or neutrophils. Listerial infections Infection in Pregnancy • 26-30 weeks gestation: decline in cellmediated immunity • Listeria may proliferate in placenta – Acute febrile illness – Arthralgia – Headache – Backache Infection in Pregnancy • Result of infection in pregnancy: – Stillbirth, neonatal death (22%) – Premature labour – Spontaneous abortion if amnionitis • Untreated bacteremia self-limited • Early antimicrobial therapy results in healthy infant • CNS infection rare in pregnancy Neonatal infection 1. Granulomatosis infantiseptica • • • • Disseminated listerial infection Caused by in utero infection Infant stillborn or dies within hours of birth Widespread microabscesses and granulomas, especially in liver and spleen • Listeria visible in meconium Neonatal infection 2. Early-onset sepsis syndrome • Acquired in utero • Associated with prematurity • Bacteria found everywhere, but highest concentrations in newborn lung and gut, suggesting acquisition from infected amniotic fluid rather than hematogenous spread. Neonatal infection 3. Late-onset meningitis • Acquired from birth canal at delivery • Occurs at ~2 weeks of age in term infants CNS Infection • Listeria has a tropism for the brain, especially brainstem, and meninges • Meningitis most frequent listerial infection • 5th most common cause of bacterial meningitis, but has highest mortality (22%) • 3rd major cause of neonatal meningitis • 2nd major cause of meningitis in elderly • Most common cause bacterial meningitis in pts with immuno-compromise Unique features of Listeria meningitis • Presentation may be subacute • Neck rigidity less common (only 80% of adults) • Movement disorders more common (ataxia, tremors, myoclonus) (15-20%) • Seizures more common (25%) • Fluctuating mental status common • Positive blood cultures more likely (75%) Unique features of Listeria meningitis • CSF findings: – Negative gram stain (60%) – Glucose level not low (normal in >60%) – Mononuclear cells predominate (30% cases) CT brain of a normal 3 week old Plain CT of a 2 week old baby with Listeria meningitis Periventricular enhancement suggests ventriculitis Diffuse parenchymal hypodensity. Edema. Other Listeria infections • Endocarditis – Affects both native and prosthetic valves – 7.5% of adult listerial infections – Rarely seen in children • Febrile gastroenteritis – In healthy, nonpregnant pts: self-limited diarrhea, nausea, vomiting, fever • Local infections – Seen in vets and farmers handling poultry Listeriosis Diagnosis Consider Listeria in: • Neonatal sepsis or meningitis • Meningitis/ parenchymal brain infection in: – – – – Pt with HIV, hematologic malignancy, transplant, steroids Subacute presentation Adults >50 years Gram-positive bacilli or “diptheroids” in CSF or blood • Subcortical brain abscess • Fever during pregnancy • Foodborne outbreak of febrile gastroenteritis in which routine cultures fail to yield a pathogen Listeriosis diagnosis • Isolation of L. monocytogenes from CSF, blood • MRI superior to CT for identifying parenchymal brain involvement, especially in the brainstem Listeriosis Treatment Listeriosis treatment • Meningitis: – Ampicillin + gentamicin x 21 days – or TMP-SMX (Trimethoprim/sulfamethoxazole) x 21 days – Avoid corticosteroid therapy (?) to avoid impairment of cellular immunity • Bacteremia only: – Amp + gent (or TMP-SMX) x 14 days Listeriosis treatment • Rhombencephalitis or brain abscess: – treat minimum 6 weeks – Follow with serial MRI or CT scans • Listerial endocarditis: – treat 4-6 weeks Listeriosis treatment • Always include ampicillin in empiric tx for septicemia or meningitis in infants < 3 mo. • Withhold iron replacement tx during listeriosis infection • ? Combination of TMP-SMX + amp may have lower rate of tx failure with fewer neurologic sequelae than amp + gent. No cheese please! Listeriosis prevention For everyone: • Thoroughly cook raw food from animals • Thoroughly wash raw vegetables • Keep uncooked meats separate from other foods • Avoid raw milk • Wash hands, knives, cutting boards after handling uncooked foods Listeriosis prevention In immunocompromised, elderly, pregnancy: • Avoid soft cheeses (feta, Brie, Camembert) • Reheat left-overs and ready-to-eat foods (e.g. hot dogs) until steaming hot before eating • +/- avoid deli foods and reheat cold cuts before eating