Listeria monocytogenes is an uncommon infection in an immunocompetent population. Listeria is known to veterinarians since the early 1900s as a cause of spontaneous abortions in many species and of circling disease or basilar meningitis in sheep. Of seven Listeria species, only Listeria monocytogenes is pathogenic for humans.¹ Recently, the whole genome of L. monocytogenes was sequenced.²

Since 1980, three major outbreaks of human listeriosis were reported in North America,^3,4,5 and a fourth was reported in Switzerland.⁶ In all outbreaks, a commercial food product was implicated as the source of infection. These outbreaks raised widespread public concern. In a Centers for Disease Control (CDC) study, 11% of all refrigerator food samples were contaminated with listeria.^7,8

Listeria has a unique predilection for otherwise healthy pregnant women, but it also affects neonates and other immunocompromised hosts, including the elderly. Pregnant women have a 12-fold increased risk to acquire listeriosis after consumption of contaminated food, compared with a normal population.⁹ Immunosuppression associated with pregnancy results in suppression of cell-mediated immunity in the placenta, perhaps from a high concentration of maternal hormones and other mechanisms.^10,11 In addition, women with multiple pregnancies have a four-fold greater risk of listeriosis than those with singletons.¹² Congenital infection can result in either stillbirth or early-onset neonatal listeriosis. Early onset neonatal listeriosis has a poor prognosis. Late-onset listeriosis acquired at delivery has a better prognosis for the newborn.¹³

A national food-monitoring practice and laboratory surveillance was put in place in 1992. A population-based active surveillance project by the CDC estimated the incidence of perinatal listeriosis decreased between 1989 and 1993 from 17.4 to 8.6 per 100,000 births.¹⁴ In the Los Angeles epidemic in 1985, 65.5% of 142 cases of listeriosis involved pregnant women.¹⁵ As a result of the human listeriosis outbreak in Los Angeles, this infection was made reportable in California. Among the elderly (older than age 70 years) the incidence is almost 12 cases per 10 million. The overall mortality in the general adult population was 35%, but it ranges from11% in persons younger than age 40 years to 63% in persons older than age 60 years. Mortality for the three recent epidemics in North America for adults and neonates ranged from 27% to 33%.¹⁶

Only L. monocytogenes is an important human pathogen. All listeria are short (.5 × 1 to 2 micrometers), regular, Gram-positive, catalase-positive, nonacid-fast, nonsporulating, facultative anaerobic rods. Morphologically, they are indistinguishable from diphtheroids and are, therefore, sometimes mistaken for contaminants. They generally occur singly or in short chains, but palisade and Y-form arrangements can lead to confusion with Corynebacterium. The occasional rod more than 10 micrometers in length resembles Erysipelothrix. Coccoid forms, often seen in broth cultures or smears from infected tissue, can be mistaken for streptococci. Gram stains from older cultures and incompletely treated clinical cases may even appear Gram-negative.

Listeria are not capsulated and exhibit a characteristic tumbling motility at 20 °C to 25 °C but not at temperatures above 35 °C. This motility is produced by approximately six flagella, which are absent from cultures at 37 °C. Carbohydrates are required for growth. All pathogenic strains of Listeria (L. monocytogenes, Listeria ivanovii, and some Listeria seeligeri) produce β-hemolysis on most types of blood agar.

Many aspects of the epidemiology of listeriosis are unclear because of the lack of a sensitive method for strain identification, the several-week incubation period of the disease (11 to 70 days), the sometimes mild or asymptomatic nature of infection, and the fact that listeriosis was not a reportable disease in the United States until 1986 and, since then, it was reportable only in California.¹² Despite the implication of food sources in the recent epidemics, the mode of transmission remains obscure. L. monocytogenes has been recovered from dust, soil, water, sewage, decaying vegetation, at least 42 species of wild and domestic mammals, and 17 avian species, crustaceans, pond trout, ticks, and flies. Among food sources (Table 1), milk products (particularly soft cheese), and uncooked vegetables, fish and shellfish, ready-to-eat meat products, ground beef, and poultry have all been found to contain the organism.¹⁶ In addition, a human reservoir is suggested by isolation of the organism from human feces at rates ranging from .6% to 16% of the population at any given time.¹⁷ In longitudinal studies, up to 70% of the population harbor the organism in their gastrointestinal tract for short periods.¹⁶

Table 1. Dietary Recommendations for Preventing Foodborne Listeriosis

The great ubiquity of the organism suggests that exposure usually does not result in disease. Greater epidemiologic knowledge may allow identification of primary sources of infection and control of disease clusters but may not greatly affect the incidence of sporadic disease. An understanding of the pathogenesis of listeriosis will help explain why disease occurs as a result of some exposures and not others, and which persons may be at increased risk

The portal of entry of the organism is variable, but recent implication of food sources of infection has focused attention on the gastrointestinal tract. Two studies using an in vitro system of human colon carcinoma cells demonstrate the ability of pathogenic listeria to induce their own phagocytosis and replicate readily within these enterocyte-like cells.^18,19 These activities appear to be dependent on two virulence factors of the organism. An extracellular 60-kd protein appears essential to trigger endocytosis of Listeria by nonprofessional phagocytic cells.²⁰ Listeria is a bacteria that is able to survive and multiply in every nucleated cell of the body. Using factors such as internalin A, Listeria produces hemolysin and phospholipases inside the host cell to promote their entry into the cytoplasm from the phagosomal compartment. In the cytoplasm, Listeria polymerizes actins from the host cell cytoskeleton to permit movement of the bacteria around the host cell until it localizes under the host cell wall to produce a bacterial surface protein, ActA. As a reaction to the presence of bacteria, the host cell membrane produces extrusions that penetrate neighboring cells and serve as a bridge to pass L. monocytogenes to other cells. This cell-to-cell spreading mechanism evades the host cell's defense mechanisms.^21,22

Once bacteria enter the bloodstream, three types of host responses occur in immunocompetent adult animals. Initially, approximately 90% of invading organisms are taken up and destroyed by the resident tissue macrophages of the liver and spleen. However, surviving organisms can multiply within susceptible macrophages and grow in the liver and spleen. During this time a nonspecific, T cell-independent natural host resistance occurs. Monocytosis-producing agent, an extractable lipid of L. monocytogenes, induces the production of host factors (e.g., factor-inducing monocytopoiesis and endogenous factor) that cause the proliferation of bone marrow monocyte precursors. This results in an exodus of young macrophages from the bone marrow that contain increased bactericidal activity over older fixed tissue macrophages. This phase is under genetic control, and certain inbred strains of mice lack the ability to mount this response.²² Such animals are not able to control the multiplication of organisms, and by day 2 or 3 they generally die of fulminating infection before specific immunity develops.²³ Some humans also may have this genetic defect.

The number of viable bacteria decreases 3 or 4 days after the onset of infection as acquired resistance develops. T cell-dependent activity that can be seen by day 5 results in a rapid increase in the number of activated macrophages in infected tissues. This process has been well studied in the mouse.²⁴ Listeria are initially phagocytized by blood monocytes and tissue macrophages, which process the bacterial antigen and subsequently produce a variety of cytokines. Interleukin-12 (IL-12), secreted by the macrophage, causes natural killer (NK) cell activation, thereby producing interferon gamma, which stimulates a proinflammatory response. The release of tumor neurosis factor alpha (TNF-) by monocytes and macrophages, in turn, stimulates polymorphonuclear leukocytes and other macrophages. Macrophages with Listeria also release interleukin-1 (IL-1), which induces lymphocyte to proliferation and activation.²⁴ The characteristic granulomas of listeriosis are the pathologic manifestations that encompass this entire process and provide the microenvironment to develop acquired resistance against Listeria.

The likelihood that exposure to Listeria causes infection depends on the inoculum size, host resistance, and virulence factors of the particular species. Recognized virulence determinants of L. monocytogenes include listeriolysin O, catalase, superoxide dismutase, and the surface components' monocytosis-producing activity, immunosuppressive activity, delayed-type hypersensitivity protein, and protein p60²⁵. Protein p60 and listeriolysin O are accepted as essential virulence factors

Pregnancy is associated with a certain degree of depressed cell-mediated immunity to prevent rejection of the fetal allograft. Concentrations of estradiol, progesterone, and hydrocortisone are three-times to 250-times greater in pregnant than in nonpregnant women. Corticosteroids suppress both lymphokine activation of macrophages and their phagocytic activity.²⁶ Alpha-fetoprotein (AFP) at physiologic concentrations inhibits macrophage expression of class II gene products of the major histocompatibility complex in vitro (Ia in the mouse).²⁷ AFP also generates suppressor cells. Acute thymic involution can occur with stress-induced increases, particularly with the already increased corticosteroid levels that exist in the latter half of gestation. With thymic involution, T cells are mobilized from thymus to spleen resulting in an increased ratio of suppressor to helper T cells.²⁶ Several other factors such as human chorionic gonadotropin (HCG), pregnancy-associated 2-glycoprotein, and IgG blocking antibody have been linked to a selective decrease in cell-mediated immunity during pregnancy. The result of these changes in pregnancy is an increased susceptibility to Listeria.

A pregnancy-associated defect in cell-mediated immunity seems to predispose rodents toward infection with Listeria. In a rat model, pregnant animals demonstrated a lower LD50 to the organism than nonpregnant controls.²⁸ In pregnant mice, the mortality after primary infection with L. monocytogenes was significantly greater and death occurred earlier than in virgin mice. Bacterial growth kinetics in the murine model implicates a pregnancy-related decrease in T cell-dependent acquired resistance.²⁹

The reported mechanisms of depression of cell-mediated immunity in human pregnancy could certainly be responsible for the increased susceptibility of pregnant women to listeriosis. Additionally, factors common to pregnancy such as iron supplementation and antacid use may also predispose to infection.³⁰ Listeria grows more rapidly and to greater numbers in iron-treated mice than in nontreated controls, which results in a mean reduction in LD50 of more than 2 × 10³ organisms.³¹ Antacid use also may be a risk factor. Antacids increase the gastric pH, which may increase the inoculum by allowing more organisms to survive after ingestion. Antacids were associated with an outbreak of L. monocytogenes.³²

The immune system of the human neonate is not fully competent at birth. Some of the developmentally determined immune defects appear to predispose the neonate to infection with Listeria. Newborn serum has negligible IgM and low concentrations of classical complement pathway factors. Listeria is opsonized primarily by IgM in the classical complement pathway³³ and the organism may have an advantage over the newborn host, particularly in the lung and cerebrospinal fluid (CSF), which are characteristic sites of neonatal infection. Unrestricted growth of Listeria in these sites can overwhelm the newborn's defenses.

Neonatal T cells produce decreased amounts of IFN-γ in comparison with adult cells because of intrinsic limitations and regulatory influences not present in adults.³⁴ This would limit the production of activated macrophages so essential to eradicate Listeria in vivo. In addition, monocyte-derived macrophages from human neonates release significantly less superoxide anion in response to lipopolysaccharide priming than those of adults.³⁵ This may reflect a decreased functional ability of newborn activated macrophages to kill bacteria. NK cells also may play a role in acquired resistance to Listeria, because migration of NK cells into mouse peritoneum occurs at the same time as destruction of the organism. NK activity in humans is low at birth and increases gradually with age. However, NK cells are not required during a Listeria infection,³⁶ because macrophages provide an alternative pathway to kill Listeria.

An age-related susceptibility of rats occurs with L. monocytogenes, and the greater susceptibility of the young animals is attributed to a defect in acquired resistance. This conclusion was based on a similar bacterial count in tissues, bacterial clearance from blood, and mononuclear cell response between young and older animals for the first 3 days after infection, but a marked improvement among older animals at 5 days.²⁸ The cause of this defect in acquired resistance or T cell-mediated immunity among newborn animals has been explored in limited detail. Neonatal mice have a profound deficit of Ia-bearing, antigen-presenting, peritoneal macrophages and splenic accessory cells that results in markedly diminished helper T cell activity. AFP is a potent suppressor of Ia expression and may be responsible for this phenomenon in mice, because the decrease in AFP levels mirrors increases Ia-bearing cells.²⁷ Failure of phagocytic cells to effectively present antigen to helper T cells results in no activation of macrophages or immunologic memory cells. In 15 mother–infant pairs followed-up 12 to 18 months after a perinatal Listeria infection, mothers demonstrated increased humoral and cell-mediated responses to Listeria over noninfected control mothers, while infected infants had no increase in a specific immune response to Listeria. This observation suggests that human neonates are particularly susceptible to Listeria infection because of a deficit in acquired resistance, although the exact mechanisms remain to be defined.

Although listeriosis is 100-times to 300-times more common in patients with AIDS than in an age-matched non-HIV-infected population,^7,39 listeriosis remains an uncommon in this group. The low incidence of listeriosis in AIDS seems surprising because T lymphocytes are crucial to develop acquired resistance against Listeria and CD4 T lymphocytes are reduced in HIV infection. The reasons for this are not clear, but several experimental findings may be relevant. Human blood monocytes and neutrophils have an innate ability to kill Listeria without helper T cell activation. Further, CD8 T cells possess the ability to protect against Listeria, independent of CD4 lymphocytes. Also, there is some evidence for the existence of a T cell-independent, IFN-γ-dependent pathway for macrophage activation that would partially inhibit Listeria growth. Perhaps in combination these mechanisms provide a sufficient defense against listeriosis in most patients with AIDS and compensate for the defect in the CD4 T lymphocyte population.⁴⁰

Listeriosis is most frequently diagnosed during the third trimester, although cases have been documented throughout pregnancy. The increase of listeriosis as pregnancy progresses maybe related to the decline in cell-mediated immunity that occurs in pregnancy.⁴¹ Maternal symptoms may be mild and nonspecific and bacterial cultures are not routinely performed on all aborted or stillborn fetuses, so it is unclear how often Listeria is responsible for early pregnancy loss. One French study cultured L. monocytogenes from 1.6% of such pregnancies.¹⁶

The disease generally manifests itself in pregnancy as a flu-like illness with fever, headache, and myalgias, although 25% of culture-positive patients report no symptoms. The fever may be low-grade or significant, ranging from 97.8°F to 104.2°F.⁴² Gastrointestinal symptoms, including diarrhea and abdominal cramping, may also occur but are less common. This prodrome marks a bacteremic phase and probably represents the point at which the organism hematogenously disseminates across the placenta. Labor often follows the bacteremic phase by 2 to 14 days.²⁴ Although maternal symptoms may have resolved by labor, recurrent fever in labor is common. White blood cell counts are generally normal to mildly elevated without monocytosis.⁴² Meconium-stained amniotic fluid is common.²⁴

Listeriosis is rarely serious for the pregnant woman and symptoms generally resolve after delivery with or without antibiotic therapy. Termination of the pregnancy not only eliminates the principle reservoir of infection but also allows the mother's immune system to return to full competency. Case reports of untreated maternal listeriosis demonstrate that infection of the fetus is not invariable.⁴³ However, early antepartum treatment clearly improves neonatal outcome.⁴² Antibiotic therapy may also eradicate asymptomatic carriage in the mother, because L. monocytogenes can persist in cervical/vaginal secretions for several weeks after perinatal listeriosis.⁴⁴ This may be more important for infection control than maternal welfare. Rarely, Listeria produces more severe manifestations during pregnancy such as meningitis,⁴⁵ adult respiratory distress syndrome,⁴⁶ and endocarditis.⁴⁷

There is no convincing evidence that L. monocytogenes is an etiologic agent of habitual abortion in humans,³⁰ as it is in rabbits. In a 1960 study, the organism was cultured from the cervical/vaginal secretions of 25 of 34 women with recurrent abortion and none of 87 control women,⁴⁸ but these results were not replicated in several subsequent studies.^49,50,51

Listeriosis in infants has two different presentations that undoubtedly represent different modes of acquisition. Early-onset disease occurs within the first 7 days of life in most cases or soon after birth. The majority of affected infants are premature as a result of an in utero infection acquired by hematogenous dissemination from the mothers across the placenta. Infection from the maternal genital tract has also been described.⁵² Preceding maternal illness is common, with flu-like symptoms presenting most commonly. Blood cultures from these mothers are often positive for L. monocytogenes. Cervical and rectal cultures also are often positive. Clustering of cases in an outbreak of epidemic listeriosis is also a common in early-onset disease.

Newborns with early-onset listeriosis generally have passed meconium in utero and may have fetal distress on intrapartum fetal heart rate (FHR) tracings,⁵³ but uniformly lack FHR accelerations.⁴² Cyanosis, apnea, and respiratory distress are presenting symptoms, and a radiographically nonspecific pneumonia is common. Severe infection called granulomatosis infantisepticum causes skin lesions of slightly elevated, 1- to 2-mm pale patches on a bright erythematous base best seen on the infant's back and lumbar area. Disseminated granuloma abscesses involve the liver, spleen, adrenal glands, lungs, esophagus, the posterior pharyngeal wall, and placenta. Although not pathognomonic, the gross and microscopic picture of the placenta in listeriosis is sufficiently distinctive to permit a presumptive diagnosis. Gram-positive rods are seen within the necrotic centers of villous and decidual microabscesses and within the membranes and umbilical cord.²⁴

Laboratory features of early-onset listeriosis are nonspecific and do not help distinguish this from early-onset group B streptococcal or any other bacterial infection. Leukocytosis with immature cells may be present, although neutropenia is more characteristic of severe infection. Thrombocytopenia sometimes occurs and anemia is common, probably secondary to the hemolysin listeriolysin O.

Late-onset neonatal infection occurs from 1 to 8 weeks of life and typically affects full-term infants of mothers with uncomplicated pregnancies. The infants are usually healthy at birth and symptoms manifest at a mean of 14 days of life.¹⁶ This feature strongly implicates a postpartum acquisition of the organism from the maternal genital tract. Clusters of late-onset listeriosis in nurseries or associated with delivery rooms imply horizontal and nosocomial transmission are possible.¹⁶

In more than 95% of late-onset cases, meningitis is the predominant manifestation with fever and irritability the presenting clinical symptoms. Often infants do not appear excessively ill. Laboratory features do not distinguish Listeria from other causes of bacterial meningitis. The cell count in the CSF is usually high, with polymorphonuclear leukocytes predominating, but monocytosis may be present in long-standing disease. Gram stain of the CSF is not diagnostic because of infrequent detection and of atypical morphology of the organism. Mortality of late-onset listeriosis is low, except in severe disease or when diagnosis and treatment are delayed. Morbidity and long-term sequelae are also uncommon.²⁴

In nonpregnant adults and children beyond the neonatal period, listeriosis is principally a disease of the immunocompromised patients with cancer or AIDS, transplant recipients, and others using immunosuppressive therapy including corticosteroids, the elderly, and those with diabetes, alcoholic and nonalcoholic liver disease, chronic renal disease, and/or collagen vascular diseases. However, 30% to 54% of adults with listeriosis have no apparent immune system compromise.

From 30% to 55% of nonperinatal cases of listeriosis present with meningitis. Nuchal rigidity is seen in 85% of cases, fever is common, but most have subacute illness. The CSF white blood cell count can vary from 100 to 10,000 per millimeter.^15,16

Polymorphonuclear leukocytes predominate in the CSF in 70% of cases, but monocytes and macrophages can occur.²⁴ Protein levels in the CSF are usually elevated and high values are a poor prognostic sign. Glucose levels in the CSF are reduced in half of cases and low glucose levels are also a poor prognostic sign. Gram stains of spinal fluid demonstrate Listeria in less than 40% of cases, although CSF cultures are usually positive. Listeria on Gram stains an easily be confused with pneumococci or diphtheroids. Blood cultures yield the organism in 60% to 75% of patients with a central nervous system (CNS) Listeria infection.

The less common, nonmeningitis infections of the CNS include cerebritis, brain stem abscesses, and spinal cord encephalitis. In these forms, fever is common but nuchal rigidity is rare. Patients may present with symptoms ranging from subtle personality changes to ataxia, tremors, seizures, and coma. Fewer than 50% of spinal fluid cultures are positive in these infections and diagnosis is generally based on a positive blood culture.¹⁶ Magnetic resonance imaging can identify the location and degree of CNS involvement.

Endocarditis can occur in patients with a prosthetic valve. Focal Listeria infections occur primarily in the immunocompromised host and include endophthalmitis, septic arthritis, liver abscess, cholecystitis, peritonitis, and pleuropulmonary infections.¹⁶ These infections result from a bacteremic phase that can go undetected because of nonspecific symptomatology. Focal cutaneous infections occur in veterinarians, farmers, and laboratory workers from direct exposure to the organism.

Culture of L. monocytogenes is the only reliable means to implicate the organism as the cause of infection. In the clinical setting of bacteremia or sepsis, blood cultures are mandatory, and with meningitis, CSF culture is necessary. Vaginal and rectal cultures should also be obtained in symptomatic patients. In perinatal listeriosis, culture can be obtained of urine, amniotic fluid, cervical material, meconium, gastric aspirate, placenta or fetal membranes, pus from skin lesions, and tissue obtained at autopsy. Blood, CSF, and pus should be submitted to the laboratory without any additives. Recovery of the organism from other clinical specimens may be enhanced by Stuart's pH-stabilizing transport medium. Specimens not sent to the laboratory immediately should be refrigerated.

L. monocytogenes can be identified on most bacteriologic culture media. Recovery from contaminated specimens is more difficult. Because Listeria species are not nutritionally demanding, selective media that suppress the growth of other organisms is more useful than enrichment media. Most workers in the field now recommend addition to culture medium of nalidixic acid and potassium thiocyanate to inhibit Enterobacteriaceae and acridine dye (e.g., acriflavine) to inhibit Streptococcus faecalis. The presence of short, Gram-positive rods by Gram stain in placental or CSF specimens supports a presumed diagnosis of listeriosis, but the organism is easily confused with streptococci, diphtheroids, and even Haemophilus. Serologic tests are not reliable enough to diagnose listeriosis, and culture of the organism remains the only reliable method to identify infection.

No prospective clinical therapeutic trials have been performed for listeriosis. However, Listeria is sensitive to many antibiotics and antibiotic resistance is rare. Ampicillin (6 g per day) or penicillin is recommended as the treatment of choice, but these antibiotics have a delayed response in the CSF. Thus, gentamicin is added to ampicillin or penicillin for synergy in serious infection, especially with CNS infection.^16,54 Ampicillin and gentamicin are synergistic in laboratory studies and are bactericidal against most strains of L. monocytogenes tested.⁵⁴ Trimethoprim-sulphamethoxazole (TSM-SMX) is bactericidal and reaches good CSF levels.⁵⁵ TSM is contraindicated in the first trimester of pregnancy for teratogenic concerns, and the displacement of bilirubin from albumin by sulphamethoxazole can cause kernicterus in later gestation if delivery is imminent.⁵⁶

Once infection with Listeria is diagnosed in pregnancy, intravenous therapy should be initiated with ampicillin 4 to 6 g per day in four divided does with gentamicin in three divided doses. Gentamicin doses can then be adjusted based on drug level monitoring because levels are unpredictable in pregnancy. Gentamicin can be discontinued after 1 week or with clinical improvement. Ampicillin should be continued for 2 weeks. Those with CNS infection should be treated for 6 to 8 weeks. Once maternal and amniotic fluid cultures have become negative, therapy may be continued orally with ampicillin 2 to 3 g per day.²⁴ With lack of clinical improvement or failure of the CSF to sterilize, additional drug therapy may be contemplated guided by sensitivity testing of the organism. TMP-SMX is bactericidal against isolates of L. monocytogenes at concentrations readily achievable in serum and CSF, and clinical reports have documented success with this drug combination.^57,58 Doses up to 5 mg/kg of sulfamethoxazole and 25 mg/kg of trimethoprim every 8 hours¹⁶ could be used in the clinical setting of severe resistant infection with Listeria. Imipenem and meropenem are recently approved for pediatric meningitis. Erythromycin, chloramphenicol, vancomycin, and cephalosporins are less effective. Scanning procedures might be helpful in this situation to clarify any degree of CNS parenchymal involvement. If an abscess is demonstrated, surgical drainage is an essential component of therapy.

The combination of TMP-SMX, like ampicillin and gentamicin, is synergistic and bactericidal against most strains of L. monocytogenes. In addition, both components cross the placenta producing potentially therapeutic levels in the fetus.^59,60 Actually, no case of kernicterus has ever been reported in a newborn after administration of a sulfonamide to the mother.^61,62 Treatment of bacteremia caused by L. monocytogenes in the late second or third trimester in a pregnant woman with a true penicillin allergy raises a risk-versus-benefit analysis. Maximum benefit to the fetus accrues from the eradication of Listeria and TMP-SMX best meets this objective. If an infant delivered of a woman treated with TMP-SMX is suspected to have significant bilirubin displacement, the plasma pH should be corrected to slightly above normal to decrease free bilirubin binding to tissues, intravenous albumin with minimal stabilizers should be administered to increase the available albumin binding sites, and exchange transfusion should be performed to remove excess unconjugated bilirubin and drug from the neonatal circulation.⁶³ The mortality in early-onset listeriosis is as high as 50%¹⁶ and some of the risk involved with the prevention of the disease is justifiable.

Ampicillin combined with an aminoglycoside is the preferred chemotherapy for early-onset neonatal listeriosis. Drug doses and dosing intervals are determined by age and weight of the infant.²⁴ Fourteen days of treatment is recommended routinely, with a longer course in the uncommon event of early-onset infection with meningitis.

Meningitis is the usual presentation in late-onset listeriosis in which the organism is generally more difficult to eradicate. Ampicillin, 200 to 400 mg/kg per day is recommended in 4 to 6 equal doses with an aminoglycoside. Lumbar punctures should be performed daily to monitor therapy. If the CSF does not become sterile after 2 days of therapy, further investigation by MRI is warranted. Additional drug therapy may be considered based on sensitivity testing of the recovered organism but, as in adults, experience with other drugs is limited.

Pregnant women should always be advised to consume only thoroughly cooked meat and washed vegetables, pasteurized milk and dairy products, and to avoid soft cheese to prevent listeriosis (see Table 1). In the event an outbreak of listeriosis occurs in the community, providers of health care for pregnant women must be especially vigilant because of the enhanced susceptibility of this population.

In an outbreak setting, a low threshold should exist to obtain blood, vaginal, and rectal cultures from any gravid patient with signs of sepsis or even mild flu-like symptoms suggestive of listeriosis. Cultures also should be obtained from CSF or amniotic fluid if an infection is suspected. Vaginal and rectal cultures are generally not indicated in asymptomatic individuals unless requested for epidemiologic purposes. Symptomatic women should be treated after culture; asymptomatic pregnant culture-positive patients should also be treated. Culture-negative patients who remain asymptomatic should be observed and another culture should be performed. Asymptomatic patients should be reassured.

If L. monocytogenes is recovered from an otherwise sterile medium, local health department officials should be notified to initiate an appropriate epidemiologic investigation. If a food source has been identified, those who care for pregnant women should make a special effort to inform their patients of this food risk factor.

L. monocytogenes has gained recognition as a human pathogen because of the increasing incidence and diagnosis of infections. Special measures undertaken by the Food and Drug Administration to monitor dairy products for L. monocytogenes and by the CDC to monitor sporadic cases of listeriosis result in voluntary recalls of contaminated products. The United States Department of Agriculture has a strict policy against contaminated foods. These efforts have significantly lowered the incidence of perinatal listeriosis from 17.4 per /100,000 births in 1989, to 8.6 per 100,000 in 1993.¹⁴ However, sporadic outbreaks are expected to continue, and continued vigilance is needed for this infection.

1. Boerlin P, Rocourt J, Piffaretti J-C: Taxonomy of the genus Listeria by using multilocus enzyme electrophoresis. Int J Syst Bacteriol 41:59-64, 1991

2. Glaser P et al: Comparative genomics of listeria species. Science 294:849, 2001

3. Schlech WF, Lavigne PM, Bortolusse R et al: Epidemic listeriosis: Evidence for transmission by food. N Engl J Med 308:203, 1983

4. Flemming DW, Cochi SL, MacDonald KL et al: Pasteurized milk as a vehicle of infection in an outbreak of listeriosis. N Engl J Med 312:404, 1985

5. Linnan MJ, Mascola L, Xiao DL et al: Epidemic listeriosis associated with Mexican-style cheese. N Engl J Med 319:823, 1988

6. Bula CJ, Bille J, Glauser MP: An epidemic of food-borne listeriosis in western Switzerland: Description of 57 cases involving adults. Clin Infect Dis 20:66, 1995

7. Schuchat A, Deaver KA, Wenger JD et al: Role of foods in sporadic listeriosis. I. Case-control study of dietary risk factors JAMA 267:2041, 1992

8. Pinner RW, Schuchat A, Swaminathan B et al: Role of foods in sporadic listeriosis. II. Microbiologic and epidemiologic investigation JAMA 267:2046, 1992

9. Hof H: History and epidemiology of listeriosis. FEMS Immunol Med Microbiol 35:199, 2003

10. Redline RW, Lu CY: Role of local immunosuppression in murine feto-placental listeriosis. J Clin Invest 79:1234, 1987

11. Redline RW, Lu CY: Specific defects in the anti-listerial immune response in discrete regions of the murine uterus and placenta account for susceptibility to infection. J Immunol 140:3947, 1988

12. Mascola L, Ewert DP, Eller A: Listeriosis: a previously unreported medical complication in women with multiple gestations. Am J Obstet Gynecol 170:1328-1332, 1994

13. Hof H, Lampidis R: Retrospective evidence for nosocomial Listera infection. J Hosp Infect 48:321-322, 2001

14. Tappero J, Schuchat A, Deaver KA et al: Reduction in the incidence of human listeriosis in the United States. J Am Med Assoc 272:1118-1122, 1995

15. Linnan MJ, Mascola L, Lou XD et al: Epidemic listeriosis associated with Mexican-style cheese. N Engl J Med. 319:823, 1988

16. Gellin BG, Broome CV: Listeriosis. JAMA 261:1313, 1989

17. Lamont RJ, Postlethwaite R: Carriage of Listeria monocytogenes and related species in pregnant and non-pregnant women in Aberdeen, Scotland. J Infect 13:187, 1986

18. Gaillard JL, Berche P, Mounier J et al: In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocyte-like cell line Caco-2. Infect Immun 55:2822, 1987

19. Mounier J, Ryter A, Coquis-Rondon M et al: Intracellular and cell-to-cell spread of Listeria monocytogenes involves interaction with F-actin in the enterocyte cell line Caco-2. Infect Immun 58:1048, 1990

20. Kuhn M, Goebel W: Identification of an extracellular protein of Listeria monocytogenes possibly involved in intracellular uptake by mammalian cells. Infect Immun 57:55, 1989

21. Vazquez-Boland JA, Kuhn M, Berche P et al: Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev 14:584, 2001

22. Rouquette C, Berche P: The pathogenesis of infection by Listeria monocytogenes. Microbiologia 12:245, 1966

23. Kongshavn PAL: Genetic control of resistance to Listeria infection. Curr Top Microbiol Immunol 124:67, 1986

24. Bortolussi R, Schlech WF: Listeriosis. In: Remington JS, Klein JO (eds): Infectious Diseases of the Fetus and Newborn Infant. pp 1157-1177, Philadelphia, WB Saunders, 2001

25. Jones D: Foodborne listeriosis. Lancet 336:1171, 1990

26. Weinberg ED: Pregnancy-associated depression of cell-mediated immunity. Rev Infect Dis 6:814, 1984

27. Lu CY, Changelian PS, Unanue ER: a-Fetoprotein inhibits macrophage expression of Ia antigens. J Immunol 132:1722, 1984

28. Bortolussi R, Campbell N, Krause V: Dynamics of Listeria monocytogenes type 4b infection in pregnant and infant rats. Clin Invest Med 4:273, 1984

29. Luft BJ, Remington JS: Effect of pregnancy on resistance to Listeria monocytogenes and Toxoplasma gondii infections in mice. Infect Immun 38:1164, 1982

30. Lorber B: Listeriosis. Clin Infect Dis 24:1, 1997

31. Sword CP: Mechanisms of pathogenesis in Listeria monocytogenes infection. I. Influence of iron J Bacteriol 92:536, 1966

32. Ho JH, Shands KN, Friedland G et al: An outbreak of type 4b Listeria monocytogenes infection involving patients from eight Boston hospitals. Arch Intern Med 146:520, 1986

33. Bortolussi R, Issekutz A, Faulkner G: Opsonization of Listeria monocytogenes type 4b by human adult and newborn sera. Infect Immun 52:493, 1986

34. Wilson CB, Westall J, Johnston L et al: Decreased production of interferon-gamma by human neonatal cells. J Clin Invest 77:860, 1986

35. Speer CB, Ambruso DR, Grimsley J et al: Oxidative metabolism in cord blood monocytes and monocyte-derived macrophages. Infect Immun 50:919, 1985

36. Barber EM, Pollard JW: The uterine NK cell population requires IL-15 but these cells are not required for pregnancy nor the resolution of a L. monocytogenes infection J Immun 171:37, 2003

37. Issekutz TB, Evans J, Bortolussi R: The immune response of human neonates to Listeria monocytogenes infection. Clin Invest Med 7:281, 1984

38. Jurado RL, Farley MM, Pereira E et al: Increased risk of meningitis and bacteremia due to Listeria monocytogenes in patients with HIV infection. Clin Infect Dis 17:224, 1993

39. Ewert DP, Lieb L, Hayes PS et al: Listeria monocytogenes and serotype distribution among HIV-infected persons in Los Angeles County, 1985–92. J Acquir Immune Defic Syndr and Human Retrovirol 8:461, 1995

40. Kaufmann SHE: Listeriosis: New findings–current concern. Microb Pathogen 5:225, 1988

41. Weinberg ED: Pregnancy-associated depression of cell-mediated immunity. Rev Infect Dis 6:814, 1984

42. Boucher M, Yonekura ML: Perinatal listeriosis (early onset): Correlation of antenatal manifestations and neonatal outcome. Obstet Gynecol 68:593, 1986

43. Hume OS: Maternal Listeria monocytogenes septicemia with sparing of the fetus. Obstet Gynecol 48:(S):33S-34S, 1976

44. Gray ML, Killinger AH: Listeria monocytogenes and listeria infections. Bacteriol Rev 30:309, 1966

45. Boucher M, Yonekura ML: Listeria meningitis during pregnancy. Am J Perinatol 1:312, 1984

46. Boucher M, Yonekura ML, Wallace RJ et al: Adult respiratory distress syndrome: A rare manifestation of Listeria monocytogenes infection in pregnancy. Am J Obstet Gynecol 149:686, 1984

47. Katz VL, Weinstein L: Antepartum treatment of Listeria monocytogenes septicemia. South Med J 75:1353, 1982

48. Rappaport F, Rabinovitz M, Toaff R et al: Genital listeriosis as a cause of repeated abortion. Lancet 1:1273, 1960

49. Lawler FC, Wood WS, King S et al: Listeria monocytogenes as a cause of fetal loss. Am J Obstet Gynecol 89:915, 1964

50. Ruffolo EH, WIlson RB, Weed LA: Listeria monocytogenes as a cause of pregnancy wastage. Obstet Gynecol 19:533, 1962

51. Rabau E, David A: Listeria monocytogenes in abortion. Lancet 1:228, 1963

52. Filice GA, Cantrell HF, Smith AB et al: Listeria monocytogenes infection in neonates: Investigation of an epidemic. J Infect Dis 138:17, 1978

53. Koh KS, Cole TL: Listeria amnionitis as a cause of fetal distress. Am J Obstet Gynecol 136:261, 1980

54. Scheld WM: Evaluation of rifampin and other antibiotics against Listeria monocytogenes in vitro and in vivo. Rev Infect Dis 5:(S3):593, 1983

55. Southwick F, Purich D: Intracellular pathogenesis of listeriosis. N Engl J Med 334:770, 1996

56. Silver HM: Listeriosis during pregnancy. Obstet Gynecol Survey 53:737, 1998

57. Boisivan A, Guimar C, Carbon C: In vitro bactericidal activity of amoxicillin, gentamicin, rifampin, ciprofloxacin and trimethoprim-sulfamethoxazole alone or in combination against Listeria monocytogenes. Eur J Clin Microbiol Infect Dis 9:206, 1990

58. Spitzer PG, Hammer SM, Karchmer AW: Treatment of Listeria monocytogenes infection with trimethoprim-sulfamethoxazole: Case report and review of the literature. Rev Infect Dis 8:427, 1986

59. Reid DWJ, Caille G, Kaufmann NR: Maternal and transplacental kinetics of trimethoprim and sulfamethoxazole, separately and in combination. Can Med Assoc J 112:67S, 1975

60. Silverman WA, Anderson DH, Blanc WA et al: A difference in mortality rate and incidence of kernicterus among premature infants allotted to two prophylactic antibacterial regimens. Pediatrics 18:614, 1956

61. Scholer HJ, Leimer R, Richle R: Sulphonamides and sulfones. In: Peters W, Richards WHG (eds): Antimalarial Drugs. II. Current Antimalarials and New Drug Developments, II. Handbook of Experimental Pharmacology p 141, vol 68:Berlin, Springer-Verlag, 1984

62. Kantor HI, Sutherland DA, Leonard JT et al: Effect on bilirubin metabolism in the newborn of sulfisoxazole administered to the mother. Obstet Gynecol 17:494, 1961

63. Brodersen R: Prevention of kernicterus based on recent progress in bilirubin chemistry. Acta Paediatr Scand 66:625, 1977