The Israeli Survey

Of the 24 general (acute-care) hospitals in Israel, 11 are large, with 500-1,200 beds, 8 have 300-499 beds, and 5 have <300 beds. Information on Lm infections was collected by contacting infectious disease specialists in each of the 19 larger hospitals. The specialists were asked to identify retrospectively all patients with listeriosis (as defined below) from the period 1995-1999 in their hospitals and to complete a questionnaire on each. Questionnaires were completed from 17 of the hospitals (11 large, 6 intermediate), and complementary information was retrieved from the MOH passive and active surveillance files on 4 additional hospitals (1 intermediate and 3 small). These 21 hospitals represented approximately 95% of the total acute-care beds in Israel during the study period.

One hundred sixty-one patients with Lm infection were identified. Clinical information was available for all patients except five (3%: two with positive blood cultures and one with a positive vaginal culture who were not hospitalized, and two with positive blood cultures whose hospital charts could not be retrieved).

Lm isolates were identified by standard methods in the microbiology laboratory in each medical center, then sent to the Reference Laboratory for Listeria in Jerusalem for confirmation.

Listeriosis was defined as the growth of Lm (as confirmed at the reference laboratory) from any body site. An infection in a pregnant woman and her fetus or neonate was considered a single perinatal event.

Worldwide Review

We conducted aPubmed search for studies describing nonselective, population-based surveys of Lm infections in the English language literature of the last decade (1990-2000). All case series describing at least 15 nonperinatal, nongastroenteritis infections were included in the review of nonperinatal listeriosis. All case series describing at least 15 perinatal cases were included in the review of perinatal listeriosis.

The Israeli Survey (1995-1999)

Figure 1

Figure 1. . Number of cases of perinatal and nonperinatal Listeria monocytogenes infection, Israel, 1995-1999.

Figure 2

Figure 2. . Seasonal occurrence of Listeria monocytogenes infection, Israel, 1995-1999.

The 161 cases identified during the 5-year study period included 91 (57%) nonperinatal and 70 (43%) perinatal infections. The average annual incidence during the study period was 0.6/100,000 population. The marked increase in 1998 (Figure 1) was exclusively in perinatal cases; the reason for the increase remains unclear. There were no clusters in place during any of these years. Infection occurred throughout the year, but more often during summer and fall, with 70% of cases occurring from May to October (Figure 2).

<H3>Nonperinatal Cases

Figure 3

Figure 3. . Age distribution of 87 nonperinatal cases of Listeria monocytogenes infection by immune-status group, Israel, 1995-1999.

The mean age of the 87 nonperinatal cases with available clinical information was 67 years (range 4-91), 66 (76%) were ≥60 years of age (Figure 3); 56 (64%) were male. Sixty-four patients (74%) had severe immunocompromising conditions (Table 1). Of 45 patients (52%) with malignant disease, most had received chemotherapy, steroid therapy, or both during the month before the Lm infection. Other immunocompromising conditions were chronic renal failure (11 patients, 4 of whom were on hemodialysis), chronic liver disease (10 patients, mostly with cirrhosis), and diabetes mellitus (13 patients). Some of these patients had additional immunocompromising conditions (Table 1). Twenty-three patients (26%) were not immunocompromised. Most (19 [83%] of 23) were ≥63 years of age; some had concomitant conditions not considered to be immunocompromising, including three patients with valvular heart disease, predisposing them to endocarditis. Only four immunocompetent patients were <60 years of age, including a 4-year-old girl and a 38-year-old man with primary bacteremia, a 22-year-old woman with typical pyelonephritis and Lm cultured from blood only, and a 51-year-old man who had gastroenteritis and positive blood cultures (stool was not cultured for Lm).

Clinical syndromes in the 87 nonperinatal cases were primary bacteremia in 41 (47%), meningitis in 24 (28%), bacteremia with a focal infection in 18 (21%), and focal infection without bacteremia in 4 (5%) (Table 2). Six patients with meningitis had Lm isolated from both blood and cerebrospinal fluid (CSF). Two patients with primary bacteremia had symptoms suggestive of meningitis (confusion, aggressiveness), but they died shortly after admission without having a lumbar puncture performed.

The case-fatality rate in the nonperinatal group was 38% (33 of 87). Twelve of the 33 deaths occurred within 48 hours of admission or disease onset. We observed a lower mortality rate (6 [19%] of 31) among persons who received a penicillin (mostly ampicillin) as empiric therapy, compared with those who received a penicillin only after culture results were reported (9 [30%] of 30), but this difference was not statistically significant (p=0.25). The difference in death rates in immunocompromised (28 [44%] of 64) compared with immunocompetent patients (5 [22%] of 23) had borderline statistical significance (p=0.05). There was no correlation between death and age for the whole group; however, all five immunocompetent patients who died were >80 years of age.

Worldwide Review (1990-2000)

Nine case-series of nonperinatal listeriosis and five case-series of perinatal infection matched the inclusion criteria. These reports and our study provided 1,250 cases of nonperinatal and 494 cases of perinatal listeriosis for analysis (Tables 4 and 5). Nonperinatal infection constituted, on average, 65% (1,025 of 1,583) of cases among studies that supplied this information (Table 4). In total, 1,250 cases of nonperinatal infections were reviewed; information about mortality was provided for 1,129 patients. The patients’ ages ranged from <1 year to >90 years, but most were >60 years of age. The mean ages in the different series ranged from 50 to 67 years; 60% were male. Annual incidence rate varied widely (i.e., 0.1-1.1 per 10⁵), not only between countries but also between consecutive years in the same setting. Most authors also described seasonal variation, with a peak incidence in summer possibly related to seasonal consumption of specific food products (8) or to more frequent breakdowns in food handling in higher temperatures.

Most (74%) of the persons affected in the reported cases (Table 4) were immunocompromised. Malignancy, chemotherapy, steroid therapy, organ transplantation, alcoholism, liver disease, renal insufficiency, and diabetes mellitus were most commonly reported, with few cases of acquired immunodeficiency syndrome.

With regard to clinical syndromes, the most common (47%) site of infection was the central nervous system (CNS) (Table 4), frequently associated with bacteremia. An additional 48% of patients were bacteremic without CNS involvement.

Perinatal infection constituted 34% (470 of 1,378) of cases among studies that supplied this information (Table 5). In total, 494 cases of perinatal infections were reviewed. Infection during the first two trimesters of pregnancy was almost invariably fatal to the fetus. One hundred six (21%) of the 494 pregnancies reviewed here resulted in intrauterine death.

Two hundred seventy-eight (56%) live-born infants had neonatal listeriosis and survived. Most of this neonatal infection was of early onset (209 cases), but the definition of early onset varied (from ≤5 to ≤7 days), and information concerning day of onset was incomplete in some series (Table 5). Almost all the late-onset infections (69 cases) were of the CNS. An additional 61 infants (12%) with neonatal listeriosis died from the infection in the postnatal period, for an overall intrauterine and postnatal mortality rate of 34% (167 of 494). In 49 (10%) of the affected pregnancies, the infant was born alive and without evidence of listeriosis.