Listeriosis

Listeriosis is an infection caused by Listeria monocytogenes, a Gram positive, facultatively intracellular bacterium. It is acquired through consumption of contaminated food. Unusually among foodborne pathogens, it can grow at refrigeration temperatures, which is clinically important.

Disease occurs predominantly in specific high risk populations, namely pregnant women, neonates, the elderly and immunocompromised individuals.

This reflects the organism's capacity to cause severe invasive disease specifically where cell mediated immunity is impaired or immature.

Pathophysiology and food sources

• The organism's facultative intracellular lifestyle allows it to spread directly from cell to cell, evading humoral immune defences. This explains its particular virulence in hosts with impaired cell mediated immunity.
• Its ability to cross both the placental and blood brain barriers accounts for the two most clinically significant manifestations, namely materno fetal infection and central nervous system disease.
• Recognised food sources include unpasteurised dairy products and soft cheeses, deli meats, pâté, smoked fish, and pre prepared refrigerated salads.
• Contamination and subsequent bacterial multiplication are favoured by the organism's ability to grow, albeit slowly, even at standard refrigeration temperatures.

• In pregnancy, maternal infection frequently presents as a mild, non specific febrile illness with malaise and myalgia, sometimes with gastrointestinal symptoms.
• It carries a disproportionately serious risk to the fetus, including miscarriage, stillbirth, preterm labour and severe early onset neonatal infection. The clinical significance far exceeds the generally mild maternal symptoms.
• Neonatal listeriosis presents in two recognised patterns.
• Early onset disease is acquired transplacentally and presents within the first days of life with sepsis, respiratory distress and disseminated granulomatous lesions (granulomatosis infantiseptica).
• Late onset disease typically presents after the first week of life with meningitis. It is thought to reflect acquisition during passage through the birth canal or, in some cases, nosocomial or environmental transmission.
• Central nervous system infection occurs predominantly in the elderly and immunocompromised. It presents particularly as meningitis and, distinctively, rhombencephalitis.
• Rhombencephalitis is brainstem encephalitis with cranial nerve palsies, ataxia and altered consciousness. It is relatively specific to Listeria among bacterial causes of central nervous system infection.
• Bacteraemia without an identified focus presents with fever and systemic upset without localising features. It occurs particularly in immunocompromised and elderly patients.
• Gastrointestinal illness with fever, watery diarrhoea and abdominal cramping can occur as a milder, self limiting presentation following ingestion of a heavily contaminated food source, generally in otherwise healthy individuals.

• Blood culture is the key diagnostic investigation for invasive disease.
• Cerebrospinal fluid culture and Gram stain confirm central nervous system involvement. The Gram stain shows characteristic Gram positive bacilli, though these can be subtle and easily mistaken for diphtheroid contaminants if not specifically considered.
• Cerebrospinal fluid analysis in Listeria meningitis can show a variable picture. Pleocytosis is sometimes more modest and the cell picture mixed neutrophil and lymphocyte, compared with typical bacterial meningitis.
• This is important given the potential for diagnostic confusion with a viral or partially treated bacterial process.
• Placental and, where relevant, amniotic fluid culture in suspected materno fetal infection supports diagnosis, alongside neonatal blood and cerebrospinal fluid culture where neonatal infection is suspected.
• Seek a relevant dietary history, specifically regarding high risk food consumption, in any pregnant woman, elderly or immunocompromised patient presenting with a compatible febrile illness.
• A negative history does not exclude the diagnosis, given the potentially long incubation period, which can extend up to several weeks.

• Amoxicillin (or ampicillin) is first line treatment, given intrinsic resistance of Listeria to cephalosporins.
• This is a critical point: standard empirical meningitis and sepsis regimens built around cephalosporins do not cover this organism. Amoxicillin or ampicillin must be specifically added to any empirical regimen where Listeria is a possible cause.
• This is standard practice in neonates, pregnant women, patients over fifty and immunocompromised patients presenting with suspected meningitis.
• Bacteraemia is treated with amoxicillin 2 g intravenously every four hours (or ampicillin at the equivalent dose) for a minimum of two weeks.
• Gentamicin (typically 5 mg per kg once daily, dosed and monitored according to renal function) is frequently added for the initial period of treatment, given evidence of synergistic bactericidal activity. This is particularly important given the relatively poor bactericidal activity of beta lactams alone against this intracellular organism.
• Central nervous system infection (meningitis or rhombencephalitis) requires a longer course. Give amoxicillin or ampicillin at the same high dose intravenously for a minimum of three weeks, combined with gentamicin for at least the first one to two weeks.
• This reflects the more severe nature of central nervous system involvement and the recognised risk of relapse with shorter courses.
• Trimethoprim with sulfamethoxazole (co trimoxazole) is the standard alternative for patients with significant penicillin allergy, dosed according to the site and severity of infection. It has reliable activity against Listeria and good central nervous system penetration.
• Neonatal listeriosis is treated with amoxicillin or ampicillin combined with gentamicin at neonatal weight and postnatal age adjusted doses. Duration is guided by the clinical presentation (typically fourteen to twenty one days). Manage within a specialist neonatal unit given the potential severity.
• Materno fetal infection identified antenatally is treated with high dose intravenous amoxicillin or ampicillin, with close obstetric monitoring and multidisciplinary input given the significant fetal risk.
• Treat any pregnant woman with a compatible febrile illness and relevant dietary exposure history promptly and empirically pending culture confirmation, given the potentially severe fetal consequences of delayed treatment.
• Prevention through dietary advice for high risk groups (pregnant women, elderly and immunocompromised individuals) is an important and often underemphasised measure. Advise avoidance of unpasteurised dairy products and soft cheeses, deli meats unless thoroughly reheated, pâté and smoked fish.
• Communicate this clearly during antenatal care, given the frequently mild maternal presentation but serious potential fetal consequences.