Characteristics and Outcomes of Neonates With Blood Stream Infection Due to Listeria monocytogenes.

BACKGROUND: Infection due to Listeria monocytogenes (LM) is rare in neonates; thus, its clinical presentation and outcomes are not commonly reported, especially in low- and middle-income countries. In 2017, South Africa had an outbreak due to LM. OBJECTIVE: To determine demographic characteristics, clinical and laboratory findings and outcomes of all neonates infected with LM during the outbreak period. METHODS: This is a retrospective analytic study. Clinical and laboratory records of neonates admitted at Chris Hani Baragwanath Academic Hospital from January 2017 to May 2018 with positive blood and cerebrospinal fluid culture with LM were reviewed for demographic characteristics, clinical presentation, ancillary laboratory test results and outcomes at hospital discharge. RESULTS: There were 42 neonates with positive cultures due to LM. Thirty-four (81%) were born preterm. Mode of delivery was vaginal in 78.6% and 31.0% were HIV exposed. All patients presented within the first 6 days of life as an early-onset disease. Common clinical presentation was respiratory depression (52.4%) and respiratory distress (38.1%) with 69% requiring invasive or noninvasive respiratory support. Common abnormal laboratory findings were high C-reactive protein (77.1%) followed by leukopenia (23.8%). Fourteen patients (40%) had features of meningitis based on blood and cerebrospinal fluid findings (4 culture proven). There were 11 deaths at hospital discharge, giving a mortality rate of 26.2%. CONCLUSIONS: The majority of neonates infected with LM were born preterm, raising the possibility that LM itself may have been responsible for preterm labor. All presented in the first 6 days of life and most presented with respiratory distress or depression. A high proportion had meningitis, and there was a high-mortality overall.

Listeria monocytogenes infections: Analysis of 41 patients / Infección por Listeria monocytogenes: análisis de 41 pacientes

OBJECTIVE: We describe and analyze Listeria-related demographics and clinical features to determine the predisposing conditions for severe infections. METHODS: We performed a retrospective study using positive isolation of Listeria monocytogenes from blood, cerebrospinal fluid, and other organic fluids. Electronic health records were used to determine the epidemiological and clinical features of infections caused by L. monocytogenes. Mortality and sepsis were considered dependent variables in the statistical analyses. RESULTS: We included 41 patients in an observation period of 15 years (2003-2018), with an annual incidence rate of 1.3 cases per 100,000 population. Three main population profiles were identified: newborns, pregnant women, and other adults (17.1%, 12.2%, and 82.9%, respectively). Neuroinvasive infection was present in 17 patients (41.5%). In both univariate and multivariate analyses, neurological infections, whether meningoencephalitis, rhombencephalitis, or brain abscesses, were the main risk factors for severe forms of Listeria-related infections (odds ratio 1.8, 95% CI 1.52-2.14, p = 0.01). Malignancies, whether solid tumors or hematological neoplasms, immunosuppression, and chronic diseases were not related to either mortality or severe clinical syndromes. CONCLUSION: Infections caused by L. monocytogenes were uncommon but could cause severe sepsis and mortality, especially in susceptible populations. Our study focused on neurological involvement and severe invasive forms of listeriosis. Neuroinvasive forms were the most important risk factors for severe illness but not for mortality

INTRODUCCIÓN: Describir y analizar las características demográficas y clínicas de las infecciones por Listeria para determinar los factores predisponentes para infecciones severas. MÉTODOS: Diseñamos un estudio retrospectivo utilizando los aislamientos positivos de Listeria monocytogenes en sangre, líquido cefalorraquídeo u otros fluidos orgánicos. Se obtuvieron los registros electrónicos para conseguir las características clínicas y epidemiológicas de las infecciones causadas por L. monocytogenes. Mortalidad y sepsis fueron las variables dependientes en los análisis estadísticos. RESULTADOS: Se incluyeron 41 pacientes en un período de 15 años (2003-2018), con una incidencia anual de 1,3 casos por cada 100.000 habitantes. Identificamos tres perfiles de población: neonatos, mujeres embarazadas y resto de adultos (el 17,1%, el 12,2% y el 82,9%, respectivamente). Las formas neuroinvasivas se identificaron en 17 pacientes (41,5%). Tanto en los análisis univariados como en los multivariados, las infecciones neurológicas, bien meningoencefalitis, rombencefalitis o abscesos cerebrales, fueron los principales factores de riesgo para considerar formas severas de infección por Listeria (odds ratio 1,8; IC 1,52-2,14, p = 0,01). Las neoplasias sólidas o hematológicas, la inmunosupresión o las enfermedades crónicas no estuvieron relacionadas ni con la mortalidad ni con la presencia de severidad en la infección. CONCLUSIÓN: Las infecciones causadas por L. monocytogenes son infrecuentes, pero son causa de sepsis severa y mortalidad en poblaciones susceptibles. Nuestro estudio estuvo dirigido a la infección neuroinvasiva y otras formas graves. La forma neuroinvasiva fue el factor de riesgo más importante asociado a la infección severa, pero no a la mortalidad

Tumor Necrosis Factor-α, Interleukins-12(p40), 6, and 10 levels in cerebrospinal fluid and outcome prediction in Ossimi sheep with encephalitic listeriosis.

Encephalitic listeriosis in sheep is a life-threatening disease. However, little is known about the cytokine response and their predictive value in this disease. The aim of present study was to assess the prognostic significance of Tumor Necrosis Factor-α (TNF-α), Interleukin-12(p40) (IL-12 p40), Interleukin-6 (IL-6), and Interleukin 10 (IL-10) levels in cerebrospinal fluid (CSF) in sheep with encephalitic listeriosis. Fifty-nine ewes in 14 flocks were diagnosed clinically as having listeriosis. CSF was collected and subjected to bacteriological examination and estimation of selected cytokines. Twenty-eight ewes were confirmed to be infected with Listeria monocytogenes. Based on antimicrobial sensitivity test, sheep were treated and the outcome was recorded as survivors (n=10) and non-survivors (n=18). Cutoff points for CSF cytokines were determined by Receiver operating characteristic analysis (ROC). Association between levels of CSF cytokines and outcome of listeriosis was assessed by logistic regression. TNF-α, IL-6 and IL-12(p40) levels as well as TNF-α/IL-10 ratio were significantly higher in non-survivors than survivors (p=0.002, 0.0021, 0.0033, and 0.001, respectively). However, IL-10 level was significantly lower in non-survivors than survivors (p=0.0058). ROC analysis revealed that IL-6 and TNF-α/IL-10 ratio had the highest AUC values (0.98, 0.984, respectively). Final multivariate logistic regression model showed that TNF-α/IL-10 ratio was the only variable that has predictive value for mortality in diseased sheep (p: 0.001; OR: 7.2; 95% CI: 5.7-9.8). TNF-α showed a positive correlation with IL-12ß (r=0.917) and IL-6 (r=0.965). IL-12 (p40) showed also a positive correlation with IL-6 (r=0.906). However, IL-10 showed a negative correlation with TNF-α (r=-0.915), IL-12(p40) (r=-0.790), and IL-6 (r=-0.902). In conclusion, TNF-α/IL-10 ratio may provide predictive information about outcome of encephalitic listeriosis in sheep.

Delayed cerebral thrombosis in bacterial meningitis: a prospective cohort study.

PURPOSE: To study the incidence and clinical characteristics of delayed cerebral thrombosis in bacterial meningitis patients. METHODS: We assessed the incidence and clinical characteristics of delayed cerebral thrombosis in adults with cerebrospinal fluid (CSF) culture-proven community-acquired bacterial meningitis included in a prospective nationwide study in The Netherlands performed from 2006 to 2012. RESULTS: Delayed cerebral thrombosis occurred in 11 of 1,032 episodes (1.1%). CSF culture yielded Streptococcus pneumoniae in ten patients and Listeria monocytogenes in one. Adjunctive dexamethasone therapy was administered before or with the first dose of antibiotics in 9 of 11 patients; two patients were initially not treated with dexamethasone. All patients made good initial recovery, followed by sudden deterioration after 7-42 days. Cranial imaging studies showed multiple cerebral infarctions in all patients. The outcome was unfavorable in all but one patient. In an explorative analysis, patients with delayed cerebral thrombosis had eightfold higher complement C5a CSF concentrations on the diagnostic lumbar puncture as compared in those without delayed cerebral thrombosis (p = 0.04). CONCLUSION: Delayed cerebral thrombosis is a rare but devastating complication of bacterial meningitis. Adjunctive dexamethasone therapy seems to predispose patients with bacterial meningitis to this complication. We found some evidence that this thrombotic complication is associated with activation of the complement system.

High level of heterogeneity among Listeria monocytogenes isolates from clinical and food origin specimens in Greece.

In order to examine the genetic variation of clinical and food isolates of Listeria monocytogenes in Greece, a total of 61 L. monocytogenes non-duplicate isolates, recovered from clinical specimens (n=19) and food (n=42), were serotyped and genotyped using two different Random Amplification of Polymorphic DNA (RAPD) protocols and Multiple Locus Variable Number Tandem Repeat Analysis (MLVA). Serotype group 4b, 4d, 4e prevailed (39.4%), among both clinical and food isolates, followed by serotype group 1/2a, 3a (23.0%), which nevertheless was detected only among food isolates. The most discriminatory typing protocol was MLVA, which grouped four isolates into two pairs, while the remaining isolates produced unique fingerprints. Similar results were obtained when taking into account the combination of the two RAPD protocols (Simpson index 0.999); six isolates were grouped into three pairs, two of which were the pairs that were identified also by MLVA. Single use of each RAPD protocol resulted in inferior discrimination (Simpson index 0.978 and 0.997, respectively). In conclusion, the two molecular procedures, MLVA, and the combined RAPD protocols, produced similar results, showing that L. monocytogenes isolates from clinical and food specimens were highly heterogenous and that clustering was very uncommon.

Severe invasive listeriosis--case report.

Listeriosis is a rare food borne infection which, in the invasive form, presents as bloodstream infection, central nervous system infection, materno-fetal infection, or focal infection. Certain immunosuppressive conditions have been identified as risk factors for severe invasive disease. The invasive forms of listeriosis are associated with a high case fatality rate. We present the case of a 62-year-old male with an unremarkable medical history admitted to the Iasi Infectious Diseases Hospital for fever. headache, ataxia, and diplopia. Physical examination revealed high temperature, confusion, relative bradycardia, and signs of meningeal irritation. Laboratory test showed leukocyt osis with neutrophilia. pathological CSF findings (high WBC count with predominance of neutrophils, low glucose and high protein levels), increased liver enzymes (ALAT, ASAT, AP, gammaGT), and important renal impairment (normal levels at presentation). No abnormalities at chest x-ray, cranial CT and abdominal ultrasound. CSF and blood cultures were positive for Listeria monocytogenes. Under antibiotics (ampicillin and ciprofloxacin), the course was marked by respiratory failure requiring mechanical ventilation, coma, hypotension, tachycardia. and death 12 days after admission. The particularity of this case consists in the association of the two classical forms of invasive listeriosis, meningitis and bacteriemia, with a focal infection. acute hepatitis, and a course marked by multiple organ dysfunction syndromes and exitus in a previously apparently healthy individual.

Listeria monocytogenes encephalitis in France.

PURPOSE: The authors had for aim to describe the characteristics of listeriosis encephalitis patients enrolled in a national study. METHODS: Listeria monocytogenes was identified as the forth etiology of encephalitis, in a prospective study in France, in 2007. We analyzed 12 cases with confirmed listeriosis (seven with rhombencephalitis, five with encephalitis) and compared them with encephalitis of other etiologies and with listeriosis encephalitis, mandatorily notified during the same year. RESULTS: L. monocytogenes strains were genoserotyped as IVb (n=6), IIa (n=3), and IIb (n=3). Cerebrospinal fluid (CSF) median protein level was 2.5g/L and the median WBC counts was 367cells/mm(3). Among twelve patients, seven patients had ongoing comorbidities. The case fatality rate during hospitalization was 50%. Patients presenting with listeriosis enrolled in the study did not differ from those reported to the mandatory surveillance system according to their demographical characteristics and comorbidities. They were older, presented more frequently with cancer, or were more often under corticosteroid treatment than patients presenting with encephalitis due to other etiologies. CONCLUSIONS: Neurolisteriosis has a poor prognosis, thus it should be considered early in patients presenting with encephalitis to improve its management.

CD8+ T cells primed in the periphery provide time-bound immune-surveillance to the central nervous system.

After vaccination, memory CD8(+) T cells migrate to different organs to mediate immune surveillance. In most nonlymphoid organs, following an infection, CD8(+) T cells differentiate to become long-lived effector-memory cells, thereby providing long-term protection against a secondary infection. In this study, we demonstrated that Ag-specific CD8(+) T cells that migrate to the mouse brain following a systemic Listeria infection do not display markers reminiscent of long-term memory cells. In contrast to spleen and other nonlymphoid organs, none of the CD8(+) T cells in the brain reverted to a memory phenotype, and all of the cells were gradually eliminated. These nonmemory phenotype CD8(+) T cells were found primarily within the choroid plexus, as well as in the cerebrospinal fluid-filled spaces. Entry of these CD8(+) T cells into the brain was governed primarily by CD49d/VCAM-1, with the majority of entry occurring in the first week postinfection. When CD8(+) T cells were injected directly into the brain parenchyma, cells that remained in the brain retained a highly activated (CD69(hi)) phenotype and were gradually lost, whereas those that migrated out to the spleen were CD69(low) and persisted long-term. These results revealed a mechanism of time-bound immune surveillance to the brain by CD8(+) T cells that do not reside in the parenchyma.

[Listeriosis in Tunis: seven cases reports]. / Les infections à Listeria monocytogenes à Tunis: à propos de sept cas.

Listeria monocytogenesis a Gram positive facultative intracellular bacterium that can be responsible for severe infections, affecting essentially pregnant women, immunocompromised patients at the early and later stages of life. In Tunisia, invasive L. monocytogenes infections are thought to be exceptional and limited data are available about listeriosis. We reported seven cases (five newborn children and two infants) of human listeriosis that occurred in Tunis from 2000 to 2008. The newborn children were hospitalized for suspicion of maternofoetal infections. The two infants were hospitalized for fever associated with digestive signs in one case and neurological signs in the other. L. monocytogenes-was isolated from culture of cerebrospinal fluid in four cases, peripheral samples in two cases and from blood culture in one case. Isolates identification was based on conventional methods. Antimicrobial susceptibility was realized according to the recommendation of the "Comité de l'antibiogramme de la Société française de microbiologie". All L. monocytogenes isolates were sensitive to amoxicillin and aminoside but resistant to 3rd generation cephalosporins. Investigations of the immune system were realized for the two infants including phenotypic analysis of peripheral blood cells by flow cytometry, lymphocyte proliferation assays, phagocytic cell functions and measurement of immunoglobulins as well as complement. All these explorations were normal for both infants. The outcome was fatal in only one case (a newborn child), and all the other patients recovered after adapted antibiotic treatment. In conclusion, our study shows that listeriosis is not exceptional in Tunis. Thus, it is necessary to know how to evoke this diagnosis, at any age, in order to establish an early and adapted antibiotic treatment and to avoid fatal outcome.

Antibiotic treatment for bacterial meningitis caused by Listeria monocytogenes in a patient with multiple myeloma.

Multiple myeloma is a hematolymphoid malignancy, and patients with this disorder are frequently complicated by infection. An 80-year-old woman with multiple myeloma was complicated by bacterial meningitis, and was admitted to our hospital in August 2007. She initially received ceftriaxone, but culture of cerebrospinal fluid detected Listeria monocytogenes. Ampicillin was administered, but headache and pyrexia persisted for 2 weeks, and on cerebrospinal fluid examination, the proliferation of polymorphonuclear leukocytes had not resolved. After medication with meropenem was started, the clinical symptoms completely disappeared, and the abnormalities on cerebrospinal fluid examination resolved. The patient ultimately received meropenem for 27 days, resulting in a cure. In conclusion, meropenem is useful to treat bacterial meningitis caused by L. monocytogenes. This agent is indicated when ampicillin shows inadequate effect or if the patient has an allergy to ampicillin.

Multiplex-PCR serotyping of Listeria monocytogenes isolated from human clinical specimens

The genus Listeria is composed of six species of which Listeria monocytogenes is considered the single pathogenic species that causes listeriosis in humans. Of the 13 serovars of L. monocytogenes, 1/2a, 1/2b and 4b are responsible for the majority of clinical cases. The aim of this work was to detect L. monocytogenes in the cerebrospinal fluid sample of premature newborns and to characterize this sample using biotyping, serotyping and molecular typing. The results indicated the presence of L. monocytogenesin the clinical sample studied. Moreover, the isolate was identified as the 4b serovar that was characterized by the presence of a unique 691 bp band after analysis using the Multiplex-PCR technique. The results of repeated Multiplex-PCR and sequencing have indicated that the L. monocytogenes isolate was an atypical 4b serovar, which is the first time this finding has been reported.

Activity of daptomycin against Listeria monocytogenes isolates from cerebrospinal fluid.

We tested the activity of daptomycin against 76 Listeria monocytogenes isolates from cerebrospinal fluid by broth dilution and Etest methods. For the broth dilution method, the MIC range was 1.0 to 8.0 and the MIC at which 90% of the isolates tested were inhibited (MIC(90)) was 4.0 mg/liter. For the Etest method, the MIC range was 1.0 to 4.0 and the MIC(90) was 4.0 mg/liter. Presently, daptomycin cannot be recommended for the treatment of L. monocytogenes meningitis.

Multiplex-PCR serotyping of Listeria monocytogenes isolated from human clinical specimens.

The genus Listeria is composed of six species of which Listeria monocytogenes is considered the single pathogenic species that causes listeriosis in humans. Of the 13 serovars of L. monocytogenes, 1/2a, 1/2b and 4b are responsible for the majority of clinical cases. The aim of this work was to detect L. monocytogenes in the cerebrospinal fluid sample of premature newborns and to characterize this sample using biotyping, serotyping and molecular typing. The results indicated the presence of L. monocytogenesin the clinical sample studied. Moreover, the isolate was identified as the 4b serovar that was characterized by the presence of a unique 691 bp band after analysis using the Multiplex-PCR technique. The results of repeated Multiplex-PCR and sequencing have indicated that the L. monocytogenes isolate was an atypical 4b serovar, which is the first time this finding has been reported.

Sepsis and meningitis due to Listeria monocytogenes.

PURPOSE: This study focused on the effect of immuno-compromising conditions on the clinical presentation of severe listerial infection. PATIENTS AND METHODS: Nine human listeriosis cases seen from 1991-2002 were reviewed. All adult patients, from whose blood, peritoneal fluid or cerebrospinal fluid (CSF) the L. monocytogenes was isolated, were included in this retrospective study. RESULTS: Listeriosis presented as primary sepsis with positive blood cultures in 5 cases and meningitis with positive CSF cultures in 4 cases. All of these patients had at least one underlying disease, most commonly, hematologic malignancy, diabetes mellitus, amyloidosis and hepatic cirrhosis; 55.6% had received immunosuppressive or corticosteroid therapy within a week before the onset of listeriosis. The patients were adults with a mean age of 60 years. Fever, night sweats, chills and lethargy were the most common symptoms; high temperature (> 38 degrees C), tachycardia, meningeal signs and poor conditions in general were the most common findings on admission. The mortality rate was 33.3% and was strictly associated with the severity of the underlying disease. Mortality differences were significant between sepsis (20%) and meningitis (50%) patients. CONCLUSION: Listeriosis as an uncommon infection in our region and that immuno- suppressive therapy is an important pre-disposing factor of listeriosis. Sepsis and meningitis were more common in this group of patients and had the highest case-fatality rate for food-borne illnesses.

Neonatal listeriosis.

In Western developed countries, Listeria monocytogenesis not an uncommon pathogen in neonates. However, neonatal listeriosis has rarely been reported in Taiwan. We describe two cases collected from a single medical institute between 1990 and 2005. Case 1 was a male premature baby weighing 1558 g with a gestational age of 31 weeks whose mother had fever with chills 3 days prior to delivery. Generalized maculopapular rash was found after delivery and subtle seizure developed. Both blood and cerebrospinal fluid culture collected on the 1st day yielded L. monocytogenes. In addition, he had ventriculitis complicated with hydrocephalus. Neurologic development was normal over 1 year of follow-up after ventriculoperitoneal shunt operation. Case 2 was a 28-weeks' gestation male premature baby weighing 1180 g. Endotracheal intubation and ventilator support were provided after delivery due to respiratory distress. Blood culture yielded L. monocytogenes. Cerebrospinal fluid showed pleocytosis but the culture was negative. Brain ultrasonography showed ventriculitis. Sudden deterioration with cyanosis and bradycardia developed on the 8th day and he died on the same day. Neonatal listeriosis is uncommon in Taiwan, but has significant mortality and morbidity. Early diagnosis of perinatal infection relies on high index of suspicion in perinatal health care professionals.

Listeria monocytogenes encephalitis mimicking West Nile encephalitis.

We present a case of a 50-year-old man who presented to Winthrop-University Hospital in the midst of the 2002 West Nile encephalitis (WNE) outbreak with the cardinal clinical findings of WNE, ie, fever, encephalopathy, weakness, and muscle tremors. During the summer of 2002, several cases of aseptic meningitis/viral encephalitis were admitted to our emergency room weekly. In addition, cases of WNE were being admitted at the same time. During this period we had 3 cases of WNE. Our patient presented with the clinical findings of WNE. However, laboratory and radiologic findings suggested the possibility of Listeria monocytogenes encephalitis. The cerebrospinal fluid findings included red blood cells, which, in the absence of a traumatic tap or HSV encephalitis, argue against the diagnosis of WNE but are consistent with L. monocytogenes encephalitis. Computed tomography scan showed communicating hydrocephalus, which also suggests the possibility of L. monocytogenes and argued against the diagnosis of WNE. Clinicians should be vigilant for the mimics of WNE in geographical areas where WNE outbreaks are occurring.