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 > female
- 500 annual deaths from listeriosis in the United States
- 20 " 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 milk
- Deli 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)
- 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
- Other tests:
- Blood cultures
- Stool (low sensitivity and specificity), amniotic fluid, and other body fluid cultures
- CBC 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
- Microscopic
- Nodular focal abscess
- Increased tissue macrophages
- Gram-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.
- Precautions
- Cephalosporins 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