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Listeriosis

- CSF - Gram stain: small gram-positive rods or coccobacillary forms with tumbling motility - Cell count: neutrophil or monocyte predominance - Protein: normal to moderately elevated - Glucose: normal (60% of cases) - CSF culture: need ≥10 mL for culture

- Gross: multiorgan miliary granulomatosis - Microscopic - Nodular focal abscess - Increased tissue macrophages - Gram-positive bacilli

- Precautions - Cephalosporins have higher failure rates, as do chloramphenicol and vancomycin.

para>Infected fetuses are often stillborn or premature.

Up to 50% mortality in treated neonates

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EPIDEMIOLOGY

Incidence

  • 2008: general U.S. population of foodborne listeriosis: 0.29/100,000 people
  • 2011: A 28-state outbreak from contaminated cantaloupes infected 146 people, with 30 deaths.
  • Particularly affects neonates (<1 month) and elderly (>60 years)Predominant sex: male > female500 annual deaths from listeriosis in the United States20 " ô65% of all foodborne infection " ôrelated deaths in the United States are due to listeriosis.Pregnant women account for 27% of all Listeria cases and ~60% of cases in the age range 10 to 40 years.~70% of nonperinatal infections occur in immunocompromised patients.Neonates can have early (<7 days) or late onset (>7 days) infection.Most cases of listeriosis are sporadic (not associated with an outbreak).Listerial meningitis has a mortality rate of 20%.

Prevalence

  • Pregnancy is ~20 times more likely to manifest symptoms.
  • In AIDS patients, listeriosis is ~300 times more likely than in general population (up to 1,000 times more likely in age-matched population studies).

ETIOLOGY AND PATHOPHYSIOLOGY

  • L. monocytogenes, a small gram-positive bacillus is the primary pathogen; infection with other Listeria species is rare.
  • There are at least 13 serotypes of L. monocytogenes, but most disease is due to types 4b, 1/2 a, and 1/2 b.
  • Incubation period for invasive illness is not well established and is highly variable because it depends on bacterial load and host immunity.
  • Listeria replicates best at room temperature but can grow at refrigerator temperatures.
  • Listeria is a unique pathogen due to its intracellular life cycle.
  • After entering GI tract, Listeria is phagocytosed by active endocytosis and enters host without disturbing the normal GI mucosal structure.
  • Hematogenous dissemination occurs through the bloodstream. Crosses placental and blood " ôbrain barriers
  • Illness begins 2 to 70 days after eating contaminated food.
  • Extremely common in food supply: Listeria recovered from 15 " ô70% of raw vegetables, fish, meat, ice cream, and unpasteurized milkDeli meat is the highest risk ready-to-eat food source for L. monocytogenes; retail-sliced deli meats have higher rates than prepackaged.
  • Isolated in stool of 5% of asymptomatic adults
  • Resistance to Listeria infection is cell mediated.

RISK FACTORS

  • Age: fetus, neonate, elderly
  • Metastatic malignant disease
  • HIV infection; alcoholism
  • Renal hemodialysis
  • Immunosuppression (including corticosteroid therapy)
  • Exposure to infected animals (veterinarians, butchers); animal-to-human transmission is rare.
  • Ingesting contaminated food or drink (soft cheeses, milk, butter, pate, cold-smoked trout, hot dogs, ready-to-eat pork, and deli meats)
  • Pregnancy; fetal and neonatal disease have high mortality; difficult to diagnose in pregnancy, as patients are often asymptomatic or present with a flulike illness; requires prompt treatment to prevent fetal transfer
  • Use of proton pump inhibitors
  • Prior to hospitalization; 40% of cases exposed to high-risk foods during hospitalization (1)[C]
  • Colonoscopy

GENERAL PREVENTION

  • Counseling of pregnant women regarding the increased risk of listeriosis during pregnancy (2)[C]
  • Check http://www.usda.gov/wps/portal/usda/usdahome for recalled foods, particularly for pregnant, elderly, or immunocompromised patients.
  • Avoid handling livestock.
  • Avoid contaminated silage and sewage.
  • Avoid raw/unpasteurized dairy products.
  • Avoid soft cheeses (Mexican and feta).
  • Wash all raw vegetables carefully.
  • Wash hands after handling uncooked foods.
  • Cook leftovers, hot dogs, cold cuts, and deli meats adequately before eating.
  • Listeriosis can be effectively prevented with trimethoprim-sulfamethoxazole in organ transplant and AIDS patients (3)[B].

COMMONLY ASSOCIATED CONDITIONS

  • Pregnancy
  • Immunodeficiency; diabetes
  • Cirrhosis; hemochromatosis and iron overload (Iron is a virulence factor for Listeria.)
  • Lymphomas and leukemia
  • Solid tumors; organ transplant recipients
  • Chronic renal disease
  • Alcoholism
  • Age >60 years

DIAGNOSIS

HISTORY

  • Common symptoms: fever, watery diarrhea, nausea, headache, myalgias, joint aches
  • Severe headache, fever, stiff neck, seizures
  • Irritability, lethargy, poor feeding in neonates
  • Illness duration typically 5 to 10 days

PHYSICAL EXAM

  • May have photophobia or focal cerebral deficits/cranial nerve palsy and (rarely) meningeal signs
  • Complete neurologic exam
  • Cardiopulmonary exam to assess hemodynamic stability
  • Abdominal exam

DIFFERENTIAL DIAGNOSIS

  • Viral, bacterial, or fungal (cryptococcal) meningitis
  • Brain abscess or neoplasm
  • Tuberculosis
  • Cerebral toxoplasmosis
  • Lyme disease
  • Influenza
  • Viral or bacterial gastroenteritis
  • Infantile listeriosis, Escherichia coli infection, group B streptococci infection
  • Infectious mononucleosis
  • Sarcoidosis
  • Other infections: Staphylococcus, gram-negative Klebsiella, Candida, viruses

DIAGNOSTIC TESTS & INTERPRETATION

No (Listeria-specific) investigation is required for healthy patients with normal immune function. é á

  • Stool cultures are not very useful and are usually negative unless specifically looking for Listeria.
  • Blood cultures (75% positive)
  • Not identified well on Gram stain; in clinical specimens, Listeria can be gram variable. Commonly misidentified as diphtheroids, streptococci, or enterococci
  • Isolation of a diphtheroid from blood or CSF should prompt consideration of Listeria.

Initial Tests (lab, imaging)

  • CSFGram stain: small gram-positive rods or coccobacillary forms with tumbling motilityCell count: neutrophil or monocyte predominanceProtein: normal to moderately elevatedGlucose: normal (60% of cases)CSF culture: need ≥10 mL for culture
  • Other tests:Blood culturesStool (low sensitivity and specificity), amniotic fluid, and other body fluid culturesCBC may show neutrophilia or left shift.Other cultures in newborn: cervical, vaginal secretions, and lochia from the mother; cord blood; grossly abnormal portions of the placenta, meconium, and exudate expressed from an incised skin papule of the neonate
  • Submit serologies to certified public health laboratory. In outbreaks, serotyping is desirable.
  • Notify laboratory of concern for listeriosis and send specimens promptly.
  • Antibodies to listeriolysin O have low clinical use.
  • MRI with contrast superior to CT for patients with CNS symptoms
  • Transesophageal echocardiogram if endocarditis is suspected

Follow-Up Tests & Special Considerations

Repeat CSF analysis in 48 hours for patients not responding to appropriate antimicrobial therapy. é á

Diagnostic Procedures/Other

Lumbar puncture é á

Test Interpretation

  • Gross: multiorgan miliary granulomatosis
  • MicroscopicNodular focal abscessIncreased tissue macrophagesGram-positive bacilli
  • Bacilli with "tumbling motility " Ł on CSF wet mounts

TREATMENT

MEDICATION

  • No definitive drug of choice or duration of therapy.
  • Most healthy, nonpregnant individuals with suspected Listeria gastroenteritis require only supportive therapy (4)[A].
  • Antibiotic resistance patterns for listeriosis appear relatively stable (5).

First Line

  • Ampicillin at 4 to 6 g/day in divided doses is the first-line treatment; the dose is doubled to 8 to 12 g/day in divided doses for meningitis or severe infection. Pediatric dosing is 100 to 200 mg/kg/day in divided doses and 300 to 400 mg/kg/day in divided doses for meningitis. (Penicillin G also may be used as a first-line medication.)
  • Ampicillin is generally preferred to penicillin G.
  • Prolonged use of high-dose ampicillin (in pregnancy) improves neonatal outcome (6)[A].
  • Gentamicin and ampicillin are synergistic in vitro and are often combined for severe infections. Consider combining ampicillin with IV gentamicin: loading dose 2 mg/kg, then 1.7 mg/kg q8h until cultures negative and patient is clinically improved.
  • A minimum of 3 weeks is recommended to treat Listeria meningitis.
  • Contraindications: allergy to penicillins
  • Other regimens:High-dose ampicillin for 4 to 6 weeks is recommended for Listeria endocarditis.Patients with rhombencephalitis or brain abscess should be treated for at least 6 weeks and followed with serial MRIs.
  • PrecautionsCephalosporins have higher failure rates, as do chloramphenicol and vancomycin.

Second Line

  • Trimethoprim " ôsulfamethoxazole (8 mg/kg/day TMP PO/IV divided q6h or q12h) (Bactrim, Septra) (7)[C]
  • Other: imipenem: 2 g IV q8h in adults; 120 mg/kg/day in 3 divided doses in children; maximum dose 6 g/day
  • Listeria species are capable of transferring antimicrobial resistance (8)[C].

ADDITIONAL THERAPIES

Supportive care é á

ISSUES FOR REFERRAL

  • Maternal " ôfetal medicine and neonatologist if patient is pregnant
  • Infectious disease specialist if not improving with first-line treatment
  • Neurologist if CNS involvement

INPATIENT CONSIDERATIONS

Start IV antibiotics as soon as diagnosis is suspected. é á

Discharge Criteria

  • Clinical improvement
  • Negative CSF and blood cultures

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

  • Vitals, temperature
  • Repeat lumbar puncture at 5 to 7 days in CNS-affected patients.
  • Repeat blood cultures if endocarditis.
  • Repeat imaging studies if initially abnormal.

PATIENT EDUCATION

CDC Listeriosis Web site: http://www.cdc.gov/listeria/ é á

PROGNOSIS

High mortality rate for fetal, neonatal, and infections involving the CNS; a high rate of CNS sequelae for survivors é á

COMPLICATIONS

  • Premature delivery, stillbirth, miscarriage, neonatal death, amnionitis
  • Rhombencephalitis
  • Meningitis
  • Septicemia
  • Brain, pulmonary, hepatic, placental, lymph node, or splenic abscess
  • Endocarditis (accounts for about 7% of adult cases of endocarditis)
  • Peritonitis
  • Osteomyelitis

REFERENCES

11 Dalton é áCB, Merritt é áTD, Unicomb é áLE, et al. A national case-control study of risk factors for listeriosis in Australia. Epidemiol Infect. 2011;139(3):437 " ô445.22 Smith é áMA, MacLaurin é áTL. Who is telling pregnant women about listeriosis? Can J Public Health. 2011;102(6):441 " ô444.33 Fern â ández-Sabe é áN, Cervera é áC, L â │pez-Medrano é áF, et al. Risk factors, clinical features, and outcomes of listeriosis in solid-organ transplant recipients: a matched case-control study. Clin Infect Dis. 2009;49(8):1153 " ô1159.44 Ontario Ministry of Health and Long-Term Care. Listeria Monocytogenes: A Clinical Practice Guideline. Toronto, Canada: Ministry of Health and Long-Term Care; 2008. http://www.health.gov.on.ca. Accessed 2014.55 Prieto é áM, Mart â şnez é áC, Aguerre é áL, et al. Antibiotic susceptibility of Listeria monocytogenes in Argentina. [published online ahead of print May 11, 2015]. Enferm Infecc Microbiol Clin.66 Lamont é áRF, Sobel é áJ, Mazaki-Tovi é áS, et al. Listeriosis in human pregnancy: a systematic review. J Perinat Med. 2011;39(3):227 " ô236.77 Bouza é áE, Mu â ▒oz é áP. Monotherapy versus combination therapy for bacterial infections. Med Clin North Am. 2000;84(6):1357 " ô1389.88 G â │mez é áD, Az â │n é áE, Marco é áN, et al. Antimicrobial resistance of Listeria monocytogenes and Listeria innocua from meat products and meat-processing environment. Food Microbiol. 2014;42:61 " ô65.

ADDITIONAL READING

  • Bierhoff é áM, Krutwagen é áE, van Bommel é áEF, et al. Listeria peritonitis in patients on peritoneal dialysis: two cases and a review of the literature. Neth J Med. 2011;69(10):461 " ô464.
  • Centers for Disease Control and Prevention. Listeriosis (Listeria infection). http://www.cdc.gov/listeria/index.html. Accessed 2015.
  • Centers for Disease Control and Prevention. Vital signs: Listeria illnesses, deaths, and outbreaks " öUnited States, 2009 " ô2011. MMWR Morb Mortal Wkly Rep. 2013;62(22):448 " ô452.
  • Endrikat é áS, Gallagher é áD, Pouillot é áR, et al. A comparative risk assessment for Listeria monocytogenes in prepackaged versus retail-sliced deli meat. J Food Prot. 2010;73(4):612 " ô619.
  • Mook é áP, O 'Brien é áSJ, Gillespie é áIA. Concurrent conditions and human listeriosis, England, 1999 " ô2009. Emerg Infect Dis. 2011;17(1):38 " ô43.

CODES

ICD10

  • A32.9 Listeriosis, unspecified
  • P37.2 Neonatal (disseminated) listeriosis
  • A32.89 Other forms of listeriosis
  • A32.11 Listerial meningitis
  • A32.81 Oculoglandular listeriosis
  • A32.7 Listerial sepsis
  • A32.12 Listerial meningoencephalitis
  • A32.0 Cutaneous listeriosis
  • A32.82 Listerial endocarditis

ICD9

  • 027.0 Listeriosis
  • 771.2 Other congenital infections specific to the perinatal period

SNOMED

  • Listeriosis (disorder)
  • Neonatal disseminated listeriosis (disorder)
  • Congenital listeriosis
  • Listeria meningitis (disorder)
  • Disseminated infantile listeriosis (disorder)

CLINICAL PEARLS

  • Listeriosis is most common at the extremes of age.
  • In immunocompetent patients, 2 weeks of antibiotic therapy is sufficient for bacteremia. At least 3 weeks of therapy is required for CNS infection.
  • Diagnosis of listeriosis requires a high degree of clinical suspicion, particularly in pregnancy (where prompt recognition and treatment is critical).
  • For questions regarding safety of deli meat, contact the U.S. Department of Agriculture, 800-535-4555; http://www.cdc.gov/foodnet/index.html