INTRODUCTION — Listeria monocytogenes is an important bacterial pathogen in neonates, immunocompromised patients, older adults, pregnant patients, and occasionally, previously healthy individuals.
The treatment and prognosis of listerial infection will be reviewed here. The epidemiology, pathogenesis, clinical manifestations, and diagnosis of listerial infection are discussed separately. (See "Epidemiology and pathogenesis of Listeria monocytogenes infection" and "Clinical manifestations and diagnosis of Listeria monocytogenes infection".)
CLINICAL SYNDROMES — Treatment varies with the different clinical syndromes of listerial infection:
●Infection in pregnancy
●Central nervous system infection (meningoencephalitis, cerebritis, rhombencephalitis)
The clinical manifestations of Listeria infection are discussed in greater detail separately. (See "Clinical manifestations and diagnosis of Listeria monocytogenes infection".)
ANTIBIOTIC THERAPY — The antibiotics of choice for Listeria infection are ampicillin and penicillin G. Gentamicin is used for synergy in some patients (eg, patients with central nervous system [CNS] infection, neonates).
Regimens without gentamicin may be preferable for patients who have impaired renal function or are taking other nephrotoxic drugs, such as cyclosporine. If gentamicin cannot be used, we generally favor the combination of ampicillin plus trimethoprim-sulfamethoxazole (TMP-SMX; TMP-SMX 10 to 20 mg/kg [based on the TMP component] intravenously [IV] per day divided every 6 to 12 hours, with the higher end of the dosing range used in patients who are severely ill). (See 'Alternatives to ampicillin or penicillin' below.)
Data informing the use of specific and combination regimens for Listeria infection are mainly from observational and in vitro studies. In the MONALISA study, a nationwide prospective cohort study in France that included patients with CNS, bloodstream, and pregnancy-associated Listeria infection, the use of an active beta-lactam (eg, amoxicillin, which is available in an IV formulation in Europe) or an aminoglycoside were each associated with reduced three-month mortality on multivariate analysis (beta-lactam: 69 versus 31 percent; odds ratio [OR] 0.10, 95% CI 0.04-0.26; aminoglycoside: 66 versus 31 percent; OR 0.60, 95% CI 0.38-0.94) compared with regimens that did not include each of those agents . Amoxicillin-aminoglycoside combination therapy longer than three days had an independent protective effect on survival compared with no combination therapy (80 versus 20 percent; OR 0.35, 95% CI 0.22-0.56).
Listeria are similarly susceptible in vitro to ampicillin and penicillin, and acquired resistance to the most commonly used drugs is rare [2,3]. However, ampicillin and penicillin G demonstrate delayed in vitro bactericidal activity at concentrations attainable in the cerebrospinal fluid (CSF) . As a result, for listerial CNS infections, we add gentamicin, which is bactericidal, to ampicillin or penicillin to achieve synergy [1,5-7]. Since listerial bloodstream infections carry the risk of seeding the CNS, we similarly treat them with combination therapy as well.
Regimens containing TMP-SMX have also been described in observational studies [1,8]. In the MONALISA study described above, TMP-SMX was also associated with reduced three-month mortality (OR 0.49, 95% CI 0.26-0.92) compared with non-TMP-SMX-containing regimens . A retrospective study in 22 patients with meningoencephalitis suggested that the combination of ampicillin and TMP-SMX may be more effective than the combination of ampicillin and gentamicin .
Alternatives to ampicillin or penicillin — The approach to alternative regimens depends on the contraindication to ampicillin or penicillin.
●Patients with a suspected immunoglobulin (Ig)E mediated penicillin allergy (eg, urticaria, anaphylaxis, angioedema) can either be skin tested and desensitized if necessary or treated with an alternative regimen. Consultation with an allergy specialist may be useful to determine the best approach. (See "Rapid drug desensitization for immediate hypersensitivity reactions".)
●Patients who have a penicillin allergy that is non-IgE mediated, who otherwise cannot be desensitized to their penicillin allergy, or who require another regimen while completing the desensitization should be treated with an alternative regimen.
The primary alternative regimen is TMP-SMX (10 to 20 mg/kg [based on the TMP component] IV per day divided every 6 to 12 hours, with the higher end of the dosing range used in patients who are severely ill). When used for CNS or bloodstream infection, TMP-SMX should be coadministered with gentamicin (table 1). TMP-SMX is bactericidal against Listeria, achieves adequate levels in serum and CSF, and has documented clinical efficacy [8-12].
If neither a penicillin-based regimen (ie, ampicillin) nor TMP-SMX can be used, we usually administer meropenem (2 g IV every 8 hours in adults; 120 mg/kg per day in 3 divided doses in children, maximum dose 6 g/day) with careful monitoring for efficacy. Meropenem should be coadministered with gentamicin (table 1). In patients who have a history of an IgE mediated reaction to penicillin, meropenem can be given by a test dose procedure (algorithm 1); meropenem should generally be avoided, however, in patients who have had a serious delayed type penicillin reaction (eg, Stevens-Johnson syndrome). Meropenem has excellent in vitro activity against Listeria and has been used successfully to treat listeriosis. However, clinical failure of meropenem has also been reported [13-15]. In a retrospective study, definitive therapy of invasive listeriosis with meropenem was associated with higher mortality than treatment with penicillin .
Linezolid is also active against Listeria, but clinical experience is limited to case reports [13,17]. In addition, prolonged therapy is associated with hematologic toxicity and other adverse effects.
Avoidance of delay — Untreated bloodstream and CNS listerial infections are associated with high mortality rates; thus, prompt antibiotic therapy is important. In particular, among patients with CNS listeriosis, delay in initiation of therapy has been associated with poor outcomes. In a small retrospective case-control study that included 36 patients with Listeria meningitis, delaying appropriate antimicrobial therapy for more than six hours was associated with increased mortality (hazard ratio 2.78, 95% CI 1.13-6.87) . In a multicenter retrospective study of 100 cases of CNS listeriosis, delay in treatment was associated with neurologic sequelae and death .
The evidence supporting early initiation of empiric therapy in patients with bacterial meningitis is discussed in greater detail separately. (See "Initial therapy and prognosis of bacterial meningitis in adults", section on 'Effects of delay'.)
Duration of therapy — The optimal duration of therapy is unknown, we individualize duration based on patient characteristics, disease severity, and response to treatment. Specifically, the duration of ampicillin or penicillin (or the primary alternative antibiotic used) varies by type of infection:
●For bacteremia, we treat for at least two weeks in immunocompetent patients and for at least three to six weeks in immunocompromised patients . In the rare event that endocarditis is present, antibiotics should generally be given for four to six weeks.
●For CNS infection, we treat for at least three to four weeks in immunocompetent patients and for at least four to eight weeks in immunocompromised patients [4,5,20]. Longer durations of at least six to eight weeks are typically warranted for patients with cerebritis or brain abscesses. If initially abnormal, brain imaging findings should be substantially improved before treatment is discontinued.
Gentamicin may not need to be continued for the entire duration of ampicillin or penicillin therapy, particularly in patients at higher risk for renal and/or vestibular toxicity (eg, older adults, impaired renal function, concurrent nephrotoxins). Gentamicin is generally continued until the patient improves (usually 7 to 14 days) or, in poor responders, for up to three weeks as long as there is no nephrotoxicity or ototoxicity.
Gastroenteritis — Listerial febrile gastroenteritis is a presumptive diagnosis based on clinical manifestations and presumptive exposure in the setting of an outbreak. (See "Clinical manifestations and diagnosis of Listeria monocytogenes infection", section on 'Gastroenteritis'.)
The approach to antibiotic therapy for patients with presumed listerial febrile gastroenteritis in the absence of bacteremia depends upon the host:
●For immunocompetent patients up to age 65 with isolated listerial febrile gastroenteritis, we recommend not administering antibiotic therapy. In such patients, the illness has usually resolved (typical duration ≤2 days) by the time the organism is identified .
●For immunocompromised patients or adults older than age 65 with isolated listerial febrile gastroenteritis, we suggest oral amoxicillin (500 mg 3 times daily for adults or 875 mg 2 times daily) or TMP-SMX (1 double-strength tablet twice daily for adults) . For children >3 months, the dosing of amoxicillin is 25 to 50 mg/kg per day divided every 8 hours (maximum dose 500 mg/dose); for children ≥2 months, the dosing of TMP-SMX is 6 to 12 mg/kg of the TMP component per day divided every 12 hours (maximum single dose 160 mg TMP/dose). We usually give antibiotics for 7 days.
For patients with presumed listerial gastroenteritis in the absence of fever, we do not administer antibiotic therapy.
Invasive infection such as meningitis, meningoencephalitis, or bacteremia as a complication of gastrointestinal listeriosis is overall rare, but the risk is greatest in immunocompromised, pregnant, and older adult patients ; we thus favor treatment in these populations. However, there are no systematic data that demonstrate a reduced risk of complications with therapy of gastroenteritis. We favor oral amoxicillin over oral ampicillin (which is preferentially used in some other gastrointestinal infections) because it is better tolerated and has better systemic absorption for bloodstream protection; the lower colonic levels achieved with amoxicillin are not an issue since listeriosis is not a colonic infection.
Focal infection — A number of focal manifestations of listerial infection have been described, including oculoglandular (Parinaud's) syndrome, lymphadenitis, pneumonia, empyema, myocarditis, vascular infections (eg, mycotic aneurysms, renal hemodialysis access device infections), septic arthritis, and osteomyelitis. (See "Clinical manifestations and diagnosis of Listeria monocytogenes infection", section on 'Focal infection'.)
Treatment of patients with focal listerial infection should be individualized after considering the location of infection, immune status, drug allergies, and renal and hepatic function. Although there are no prospective studies to guide the optimal therapy of these rare manifestations, we generally favor the use of ampicillin or penicillin, each combined with gentamicin for listerial vascular and bone and joint infections (table 1). We treat all other focal listerial infections with ampicillin or penicillin alone.
The duration of therapy should be informed by the usual course of antibiotic treatment for the given condition.
Specifically, bone and joint infections often require prolonged therapy for cure. Patients with such infections should receive at least two weeks of parenteral therapy. Subsequently, the patient can be switched to oral therapy with TMP-SMX (5 mg/kg, based on the TMP component, orally every 6 to 12 hours) or amoxicillin (500 mg three times daily) to complete a total of 3 to 4 weeks for septic arthritis and 6 to 8 weeks for osteomyelitis. The precise timing of the transition to oral therapy depends upon the severity of illness, response to therapy, and the immune status of the patient. In addition, clinical judgment should be used to determine whether treatment should be extended beyond the durations described above (eg, in patients with prosthetic joints in whom a strategy of debridement with retention of the prosthesis is attempted). This decision should be made on a case-by-case basis depending upon the response to treatment. For patients with prosthetic joint infection, removal or replacement of the joint is also usually necessary . (See "Nonvertebral osteomyelitis in adults: Treatment" and "Prosthetic joint infection: Treatment".)
Pregnant patients — There are no randomized trials to assess the optimal type, efficacy, and duration of antibiotic treatment; most data are based on reports of clinical experience [24-26].
Empiric management — For pregnant patients with exposure to foods with high risk of Listeria contamination (table 2), to foods that have been recalled due to Listeria contamination, or to foods that have been implicated in an outbreak of listeriosis, the approach to empiric management depends on the clinical presentation.
While the prognosis of pregnant patients with Listeria infection is favorable, there is substantial morbidity and mortality for the fetus and neonate. (See "Clinical manifestations and diagnosis of Listeria monocytogenes infection", section on 'Pregnant patients' and "Clinical manifestations and diagnosis of Listeria monocytogenes infection", section on 'Fetal and neonatal infection'.)
Given the nonspecific findings associated with listeriosis, identifying pregnant patients requiring testing and/or treatment is difficult. In one review including 117 women with clinically suspected listeriosis, none had culture-confirmed infection; however, a separate group of 7 women with cultures obtained for evaluation of fever and preterm labor had culture-confirmed listeriosis . These findings emphasize the importance of considering listeriosis in pregnant woman with fever, particularly with signs of early onset labor and elevated inflammatory markers (high white blood cell count, high C-reactive protein); in the study above, 5 of 7 missed opportunities to consider and treat listeriosis early had these markers. Despite monitoring for clinical symptoms, providers often fail to recognize all patients needing treatment, reinforcing the importance for a high index of suspicion for maternal listeriosis and a low threshold to begin treatment in women with suspected infection.
Febrile illness — For pregnant patients with presumptive Listeria exposure (see 'Empiric management' above), relevant symptoms (including myalgia, abdominal or back pain, nausea, vomiting, or diarrhea), and fever ≥38.1°C (100.6°F), in the absence of a known alternative cause of illness, empiric antibiotic therapy should be initiated while diagnostic studies are pending. (See "Clinical manifestations and diagnosis of Listeria monocytogenes infection", section on 'Pregnant patients'.)
Subsequent management is guided by blood culture results:
●If blood cultures are positive, further management is discussed below. (See 'Bloodstream infection' below.)
●If blood cultures are negative and no alternative diagnosis is established, the optimal approach is uncertain; the decision should take into account obstetric factors and symptom severity. In general, we favor completion of a 7-day course of antibiotic therapy with oral amoxicillin (500 mg 3 times daily or 875 mg 2 times daily). TMP-SMX (1 double-strength tablet twice daily) may be used as an alternative agent; however, TMP-SMX should be avoided during the first trimester, since folic acid metabolism may be affected, and during the last month of pregnancy to avoid kernicterus in the fetus.
We favor fetal surveillance for patients with a diagnosis of listeriosis; such surveillance is also prudent in the setting of presumptive exposure and maternal fever. The optimal approach to timing and frequency of monitoring is uncertain; weekly ultrasonography during the third trimester is reasonable . There are no definitive data to guide management.
Mild illness — For pregnant patients with presumptive Listeria exposure (see 'Empiric management' above) and relevant symptoms (including myalgia, abdominal or back pain, nausea, vomiting, or diarrhea) but absence of fever ≥38.1°C (100.6°F), the optimal approach to empiric antibiotic management while cultures are pending is uncertain. In general, we suggest initiating empiric antibiotic treatment with oral amoxicillin (500 mg three times daily or 875 mg two times daily), although it is unclear whether this will improve fetal outcomes . TMP-SMX (one double-strength tablet twice daily) may be used as an alternative agent; however, TMP-SMX should be avoided during the first trimester, since folic acid metabolism may be affected, and during the last month of pregnancy to avoid kernicterus in the fetus .
Subsequent management is guided by blood culture results:
●If blood cultures are negative and no alternative diagnosis is established, the optimal approach is uncertain; the decision should take into account obstetric factors and symptom severity. In general, we favor completion of a seven-day course of antibiotic therapy with oral amoxicillin; TMP-SMX may be used as an alternative agent.
Decisions regarding fetal surveillance for patients with mild illness should be individualized based on maternal-fetal clinical status; there are no definitive data to guide management .
No symptoms — For asymptomatic pregnant patients with presumptive Listeria exposure, no empiric antibiotic treatment is warranted . Such patients should be advised to return for evaluation if symptoms develop. There is no need to alter or begin fetal surveillance in asymptomatic pregnant patients who have had a known or presumed exposure to Listeria.
Bloodstream infection — Pregnant patients with established listerial bacteremia should be treated with ampicillin (2 g IV every four hours) or penicillin (4 million units IV every four hours) . We do not typically add gentamicin to the regimen because of potential toxicity and the low risk of CNS involvement in immunocompetent pregnant patients. The duration of therapy is 14 days.
In the MONALISA study, a nationwide prospective cohort study in France that included 107 patients with pregnancy-associated Listeria infection, 85 percent received IV amoxicillin, and only 28 percent received it in combination with gentamicin for a median duration of three days; differential outcomes by regimen were not calculated among this subgroup  . Parenteral amoxicillin is not widely available, but IV ampicillin is thought to be comparable.
The main option for penicillin-allergic patients is TMP-SMX (10 to 20 mg/kg [based on the TMP component] IV per day divided every 6 to 12 hours, with the higher end of the dosing range used in patients who are severely ill). However, among pregnant patients, this drug should be avoided during the first trimester, since it may affect folic acid metabolism, and during the last month of pregnancy to avoid kernicterus in the fetus. For pregnant patients who cannot take TMP-SMX, meropenem may be appropriate. (See 'Alternatives to ampicillin or penicillin' above.)
Neonates — We usually give ampicillin plus gentamicin for neonates with listeriosis. Treatment of neonates should be exclusively by the parenteral route. Dosing is summarized in the table (table 1). Once the infant is clinically improved, gentamicin may be discontinued if the CSF is sterile; the remainder of the antibiotic course (14 to 21 days) is completed with ampicillin monotherapy.
Issues related to management of neonates are discussed further separately. (See "Bacterial meningitis in the neonate: Treatment and outcome", section on 'Other pathogens' and "Management and outcome of sepsis in term and late preterm infants", section on 'Listeria monocytogenes' and "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation".)
Antibiotic agents to avoid — Certain antibiotics are suboptimally effective against Listeria and should therefore be avoided:
●Vancomycin has been used as an alternative agent , but failures have been reported. In a case report of a hematopoietic cell transplant recipient with Listeria bacteremia who failed to respond to empiric vancomycin therapy, the causative pathogen was found to be a vancomycin-resistant species, Listeria grayi, a rare cause of invasive listeriosis . The bacteremia cleared after the treatment was changed to ampicillin.
●Both erythromycin and tetracyclines have in vitro activity against Listeria; however, they are bacteriostatic, their clinical efficacy is uncertain, and plasmid-mediated resistance has been reported . We do not recommend either agent.
●Cephalosporins are inactive in vitro and ineffective clinically . This is important because the empiric therapy of acute bacterial meningitis in immunocompromised patients should include drugs that are active against Listeria. Thus, monotherapy with an extended-spectrum cephalosporin is not adequate to cover the possibility of an infection due to Listeria.
OTHER MANAGEMENT CONSIDERATIONS
Discontinue dexamethasone — If dexamethasone is initiated for bacterial meningitis, it should be discontinued once Listeria is identified, since it has not been proven to be of benefit for Listeria meningitis . Furthermore, in a nationwide prospective study in France (the MONALISA study) that included 252 cases of central nervous system (CNS) listeriosis, its use was associated with increased mortality . (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)
Adjust immunosuppression — In patients treated with immunosuppressive drugs (eg, because of solid organ transplantation), decreasing the level of immunosuppression is desirable, although many such patients have been successfully treated for listeriosis without changing the immunosuppression regimen . In cases of invasive listerial infections (eg, CNS infection, bacteremia), we favor decreasing the dose of immunosuppressive drugs whenever feasible, particularly if there is not a prompt clinical response to initial antimicrobial therapy.
MONITORING DURING THERAPY — The response to therapy should be monitored clinically (temperature, clinical signs, and symptoms). Follow-up lumbar puncture is not routinely indicated if patients are improving as expected clinically.
In patients who fail to improve clinically (eg, are persistently febrile) after several days of therapy, we repeat blood cultures. In patients with central nervous system infection who are not improving, we repeat cerebrospinal fluid (CSF) cultures and magnetic resonance imaging. If blood or CSF cultures are persistently positive, we add trimethoprim-sulfamethoxazole to the treatment regimen (ie, use a combination regimen of ampicillin, gentamicin, and trimethoprim-sulfamethoxazole).
PREVENTION OF FOODBORNE INFECTION — The epidemiology of Listeria infection is discussed separately. (See "Epidemiology and pathogenesis of Listeria monocytogenes infection".)
We are in agreement with precautions recommended by the United States Centers for Disease Control and Prevention (CDC) as summarized below (table 2) . The general recommendations intended for all individuals include:
●Make sure that the label of queso fresco and other soft cheeses says, "Made with pasteurized milk." Be aware that Hispanic-style cheeses made from pasteurized milk, such as queso fresco, have caused Listeria infections, most likely because they were contaminated during cheese-making.
●Eat cut melon immediately or refrigerate it. Keep cut melon refrigerated at 41°F (5°C) or colder and for no more than seven days. Discard cut melon left at room temperature for more than four hours.
●Do not let juice from hot dog or lunch meat packages get on other foods, utensils, or food preparation surfaces. Wash hands after handling hot dogs, lunch meats, or deli meats.
●Store opened hot dog packages for no longer than one week in the refrigerator and unopened packages for no longer than two weeks in the refrigerator.
●Store factory-sealed, unopened lunch and deli meat packages for no longer than two weeks in the refrigerator. Store opened lunch and deli meat packages and meat sliced at a local deli for no longer than three to five days in the refrigerator.
●A food is called shelf-stable if it can be safely stored at room temperature or "on the shelf." Eating canned and shelf-stable tuna, salmon, and other fish products is not considered to increase your chance of getting sick from Listeria. However, not all canned foods are shelf-stable. Some canned foods are labeled "Keep refrigerated." Examples of such items include refrigerated smoked seafood, such as salmon, trout, whitefish, cod, tuna, and mackerel. Refrigerated smoked seafood items are often labeled as "nova-style," "lox," "kippered," "smoked," or "jerky" and typically found at seafood or deli counters of grocery stores and delicatessens.
●Unpasteurized milk from any animal is widely known as "raw milk." Unpasteurized milk may be contaminated with Listeria and a variety of other human pathogens. Raw milk used in the production of soft cheese, ice cream, and yogurt has similar risks. Thus, consumers should verify that these products are labeled as being made from pasteurized milk.
●Keep milk and milk products refrigerated at 40°F (4.4°C) or colder.
Additional recommendations for individuals at higher risk, including pregnant patients, older adults, and people with weakened immunity include:
●Avoid eating soft cheese, such as queso fresco, queso blanco, panela (queso panela), brie, Camembert, blue-veined, or feta, unless it is labeled as being made with pasteurized milk.
As soft cheeses labeled as having been made from pasteurized milk (especially the Mexican-style cheese, queso fresco) have been implicated in outbreaks of listeriosis , we suggest that pregnant and immunocompromised patients avoid not only soft cheeses made from unpasteurized milk but also soft cheeses made from pasteurized milk. Note that this recommendation extends beyond those of the CDC. (See "Epidemiology and pathogenesis of Listeria monocytogenes infection", section on 'Food epidemiology and outbreaks'.)
●Do not eat raw or lightly cooked sprouts of any kind (including alfalfa, clover, radish, and mung bean sprouts). Cook sprouts thoroughly. When eating out or buying a ready-made sandwich, avoid raw sprouts. Note that rinsing sprouts will not remove bacteria.
●Avoid eating hot dogs, lunch meats, cold cuts, other deli meats (such as bologna), or fermented or dry sausages unless they are heated to an internal temperature of 165°F (74°C) or until steaming hot just before serving.
●Do not eat refrigerated pâté or meat spreads from a deli or meat counter or from the refrigerated section of a store.
●Foods that do not need refrigeration, like canned or shelf-stable pâté and meat spreads, are safe to eat. Refrigerate these foods after opening.
●Do not eat refrigerated smoked seafood unless it is canned or shelf-stable or it is in a cooked dish, such as a casserole.
●The general recommendations given above regarding raw milk and other products made from raw milk are especially important for individuals at high risk. They include:
•Only consume pasteurized milk and milk products, including soft cheese, ice cream, and yogurt. Look for the word "pasteurized" on the label. If in doubt, don’t buy it.
•Keep milk and milk products refrigerated at 40°F (4.4°C) or colder.
General food safety recommendations can be found at FoodSafety.gov.
Nonpregnant patients — Among foodborne infections in the United States, Listeria has the third highest reported mortality rate (approximately 16 percent compared with 35 percent with Vibrio vulnificus) and accounts for approximately 19 percent of all deaths from foodborne infection . However, it should be noted that mortality rates are often subject to reporting bias. Since it is more likely that severe or fatal cases are reported and that mild cases are unreported, the actual case-fatality rate is probably lower than 16 percent. Nonperinatal listeriosis-associated deaths in the United States decreased between 1990 and 2005, paralleling the decreasing trend in incidence . (See "Epidemiology and pathogenesis of Listeria monocytogenes infection", section on 'Incidence of infection'.)
The mortality associated with Listeria infection is highly variable, being determined by the patient's underlying immune status, the site of infection, and the presence or absence of early diagnosis and early initiation of appropriate therapy when indicated.
In the MONALISA study, a nationwide prospective observational cohort study from France, three-month mortality was 45 percent in patients with bacteremia (194 of 427 patients) and 30 percent in those with central nervous system (CNS) infection (75 of 252 patients); there were no deaths among 107 pregnant patients . The strongest predictors for mortality in those with bacteremia or CNS infection were ongoing cancer, multiorgan failure, aggravation of pre-existing organ dysfunction, and monocytopenia. In those with CNS infection, mortality was higher in those who received dexamethasone and in those with positive blood cultures.
CNS infection is an important risk factor for mortality and morbidity . As an example, patients with meningoencephalitis or rhombencephalitis in different series had a 100 percent mortality if untreated and 13 to 43 percent if treated [1,20,40]. In the MONALISA study, among patients with CNS listeriosis, patients with encephalitis had threefold higher mortality than those without encephalitis (72 of 218 patients with encephalitis [33 percent] versus 3 of 34 patients without encephalitis [9 percent]) . Furthermore, neurologic sequelae are common among the survivors of CNS infection [20,22,41]. In reports of 62 patients with rhombencephalitis  and 38 patients with brain abscess , 61 percent of survivors had persistent neurologic sequelae. In the MONALISA study, among patients with CNS listeriosis, the presence of encephalitis-associated signs was the strongest parameter associated with persistent neurologic impairment (in 78 of 149 with encephalitis signs [52 percent] versus 1 of 32 without encephalitis signs [3 percent]) .
Adults with no underlying disease almost always do well. In two series of 281 and 74 patients, for example, there were no deaths in otherwise healthy patients compared with an overall mortality rate of 22 to 32 percent in patients at increased risk [40,42]. In the larger series, which excluded patients with perinatal infection, risk factors for mortality included nonhematologic malignancy, alcoholism, age ≥70 years, glucocorticoid use, and kidney disease . In a study of 30 solid organ transplant recipients with listeriosis, the 30-day mortality was 27 percent .
Listeria meningitis may serve as a marker for cancer in older patients. In a nationwide cohort study from Denmark, adult survivors of Listeria meningitis had increased cancer-related mortality during the five-year period after the diagnosis of meningitis, and the subset over 50 years of age had a twofold increased risk of being diagnosed with cancer during the same time period . Screening for underlying malignancy was recommended by the authors, especially in patients over 50 years of age.
In two prospective nationwide cohort studies from the Netherlands conducted from 1998 to 2002 and from 2006 to 2012 that included 92 adults with community-acquired Listeria meningitis, the rate of unfavorable outcomes increased from 27 to 61 percent between the earlier and later time periods . L. monocytogenes genotype sequence type 6 (ST6) increased substantially between the two periods, causing 4 percent of cases between 1998 and 2002 and 29 percent of cases between 2006 and 2012. Dexamethasone use also increased between the two periods (from 0 to 53 percent). On multivariate analysis, infection with L. monocytogenes ST6 was the sole predictor of unfavorable outcome (odds ratio 3.8, 95% CI 1.1-13.3).
Pregnant patients and neonates — Outcomes for the pregnant patients with Listeria are typically good; in the MONALISA study there were no deaths among 107 pregnant patients .
Fetal and neonatal infections can be severe, leading to fetal loss, preterm labor, neonatal sepsis, meningitis, and death [1,45-51]. In one series including more than 200 cases of pregnant patients with listeriosis, approximately one in five pregnancies complicated by listeriosis resulted in spontaneous abortion or stillbirth; approximately two-thirds of surviving infants developed neonatal listeriosis .
Fetal and neonatal adverse effects are less common if infection occurs at later gestational age . Among 11 cases of Listeria infection during pregnancy, the two cases that occurred before the third trimester (at 17 and 18 weeks gestation) resulted in fetal death, one following spontaneous abortion and the other immediately after delivery . Six of the nine patients infected during the third trimester delivered preterm and had neonates with listerial infection. The remaining three-term infants were not infected. (See "Clinical manifestations and diagnosis of Listeria monocytogenes infection", section on 'Fetal and neonatal infection'.)
Similarly, in a study from Israel of 166 cases of pregnancy-related listeriosis (which accounted for 35 percent of all Listeria cases in a ten year period), survival of the fetuses correlated with trimester, with 0, 29, and 95 percent survival with infection during the first, second, and third trimester, respectively .
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bacterial meningitis in adults" and "Society guideline links: Bacterial meningitis in infants and children" and "Society guideline links: Infectious encephalitis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Listeria (The Basics)")
SUMMARY AND RECOMMENDATIONS
•CNS or bloodstream infection – Invasive listerial infection involving the central nervous system (CNS) or bloodstream requires prompt treatment with antibiotic therapy in order to avoid poor outcomes. For nonpregnant patients (including neonates) with invasive infection, we suggest intravenous (IV) ampicillin or penicillin, each with gentamicin for synergy (table 1) (Grade 2C). Options for penicillin-allergic patients include desensitization or treatment with trimethoprim-sulfamethoxazole (TMP-SMX). (See 'Invasive disease' above and 'Neonates' above.)
For patients taking immunosuppressive agents, the level of immunosuppression should be decreased, if possible, particularly if there is not a prompt clinical response to initial antimicrobial therapy. If dexamethasone had been initiated for empiric management of bacterial meningitis, it should be discontinued once Listeria is identified. (See 'Adjust immunosuppression' above and 'Discontinue dexamethasone' above.)
In immunocompetent patients we give the primary antibiotic (eg, ampicillin) for a minimum of two weeks for bacteremia and three to four weeks for CNS infection. In immunocompromised patients, we give the primary antibiotic for three to six weeks for bacteremia and four to eight weeks for CNS infection. We continue gentamicin until the patient improves (usually 7 to 14 days) except for poor responders, whom we treat for up to three weeks, as long as there is no nephrotoxicity or ototoxicity. (See 'Duration of therapy' above.)
•Gastroenteritis – Most immunocompetent patients with presumed listerial gastroenteritis do not require antibiotics; such illnesses are almost always self-limited and invasive complications are rare. For immunocompromised patients and adults older than age 65, we suggest antibiotic therapy (Grade 2C). In such cases, oral amoxicillin or TMP-SMX are appropriate; we typically give these for seven days. (See 'Gastroenteritis' above.)
●Pregnant patients – For pregnant patients with exposure to foods with high risk of Listeria contamination (table 2), to foods that have been recalled due to Listeria contamination, or to foods that have been implicated in an outbreak of listeriosis, the approach to empiric management depends on the clinical presentation (algorithm 2). The major clinical syndromes are bloodstream infection and gastroenteritis; CNS disease is not usually seen in pregnant patients.
•Empiric management of febrile illness – While the prognosis of pregnant patients with Listeria infection is favorable, there is substantial morbidity and mortality for the fetus and neonate. Therefore, for pregnant patients with presumptive Listeria exposure (table 2), relevant symptoms (including myalgia, abdominal pain, back pain, nausea, vomiting, or diarrhea), and fever ≥38.1°C (100.6°F), in the absence of a known alternative cause of illness, we recommend administration of antibiotic therapy (Grade 1C). In such cases, we suggest initiation of empiric parenteral ampicillin rather than other antibiotic regimens (Grade 2C). (See 'Febrile illness' above.)
-If blood cultures remain negative and no alternative diagnosis is established, the optimal approach is uncertain. We complete a seven-day course of antibiotic therapy with oral amoxicillin; TMP-SMX may be used as an alternative agent but should be avoided during the first trimester and during the last month of pregnancy. (See 'Febrile illness' above.)
•Empiric management of mild symptoms – For pregnant patients with presumptive Listeria exposure (table 2) and relevant symptoms but no fever, we suggest initiating empiric antibiotic treatment (Grade 2C). In such cases, we suggest initiation of empiric oral amoxicillin rather than other antibiotic regimens (Grade 2C) (See 'Mild illness' above.)
-If blood cultures are negative and no alternative diagnosis is established, the optimal approach is uncertain. We favor completion of a seven-day course of antibiotic therapy with oral amoxicillin; TMP-SMX may be used as an alternative agent, but should be avoided during the first trimester and during the last month of pregnancy.
•Empiric management of no symptoms – For pregnant patients with presumptive Listeria exposure (table 2) who are asymptomatic, we suggest not initiating empiric antibiotic treatment (Grade 2C). (See 'No symptoms' above.)
•Bloodstream infection – For pregnant patients with listerial bloodstream infection, we suggest treatment with IV ampicillin or penicillin rather than other antibiotic regimens (Grade 2C). The duration of therapy is 14 days. TMP-SMX is an alternative in penicillin-allergic patients; however, it should be avoided in the first trimester and the last month of pregnancy. During those periods, meropenem is another alternative agent. (See 'Bloodstream infection' above.)
●Follow-up evaluation – Follow-up blood cultures are not necessary in patients who are improving as expected. In patients who fail to improve clinically (eg, are persistently febrile) after several days of therapy, we repeat blood cultures. In patients with CNS infection who are not improving, we repeat cerebrospinal fluid cultures and magnetic resonance imaging. (See 'Monitoring during therapy' above.)
●Avoiding exposure – Food products implicated in Listeria outbreaks include unpasteurized soft cheeses, melon, hot dogs, and deli meat (table 2). Milk products should be pasteurized and refrigerated at 40°F (4.4°C) or colder. Immunocompromised and pregnant patients should avoid soft cheeses even if labeled as pasteurized, deli meats, hot dogs, and raw or lightly-cooked sprouts. More extensive food safety precautions for prevention of listeriosis are summarized above. (See 'Prevention of foodborne infection' above.)