Neural Injury and Repair in a Novel Neonatal Mouse Model of Listeria Monocytogenes Meningoencephalitis.

To improve the therapy of neonatal central nervous system infections, well-characterized animal models are urgently needed. The present study analyzes neuropathological alterations with particular focus on neural injury and repair in brains of neonatal mice with Listeria monocytogenes (LM) meningitis/meningoencephalitis using a novel nasal infection model. The hippocampal formation and frontal cortex of 14 neonatal mice with LM meningitis/meningoencephalitis and 14 uninfected controls were analyzed by histology, immunohistochemistry, and in situ tailing for morphological alterations. In the dentate gyrus of the hippocampal formation of mice with LM meningitis/meningoencephalitis, an increased density of apoptotic neurons visualized by in situ tailing (p = 0.04) and in situ tailing plus immunohistochemistry for activated Caspase-3 (p < 0.0001) was found. A decreased density of dividing cells stained with an anti-PCNA-antibody (p < 0.0001) and less neurogenesis visualized by anti-calretinin (p < 0.0001) and anti-calbindin (p = 0.01) antibodies were detected compared to uninfected controls. The density of microglia was higher in LM meningitis (p < 0.0001), while the density of astrocytes remained unchanged. Infiltrating monocytes and neutrophilic granulocytes likely contributed to tissue damage. In conclusion, in the brains of LM-infected mice a strong immune response was observed which led to neuronal apoptosis and an impaired neural regeneration. This model appears very suitable to study therapies against long-term sequelae of neonatal LM meningitis.

Listeria meningitis complicated by hydrocephalus in an immunocompetent child: case report and review of the literature.

BACKGROUND: Listeria monocytogenes is a Gram-positive bacteria transmitted to human by animal stools, contaminated water and food. In children, Listeria monocytogenes typically affects newborns and immunocompromised patients often leading to invasive syndromes including sepsis, brain abscesses, meningitis, meningoencephalitis and rhombencephalitis. In healthy and immunocompetent children, Listeria meningitis is rare, but can progress rapidly and may be associated with severe complications (hydrocephalus, ventriculitis, cranial nerves palsy and cerebrospinal abscesses) and high mortality rate. CASE PRESENTATION: We describe a very uncommon case of meningoencephalitis due to Listeria monocytogenes in a 11-month-old immunocompetent girl. Cerebrospinal fluid (CSF) culture was positive on the second day. Antibiotic therapy was promptly started but the disease was complicated by neurological deterioration and decompensated hydrocephalus. The child required a very demanding pediatric and neurosurgical management and was discharged after 40 days without major sequelae. CONCLUSION: Listeria is difficult to isolate and it is not susceptible to first-line treatment for bacterial meningitis with extended-spectrum cephalosporins. Early recognition is therefore crucial for a positive outcome. Pediatricians have to perform close clinical monitoring of these children and be aware of possible complications. A review of all cases of Listeria meningitis complicated by hydrocephalus in healthy children has been performed, to provide an overview on clinical features, treatment options and outcome.

Characterization of a Listeria monocytogenes meningitis mouse model.

BACKGROUND: Listeria monocytogenes is a common cause of bacterial meningitis. We developed an animal model of listerial meningitis. METHODS: In survival studies, C57BL/6 mice received intracisternal injections with different L. monocytogenes sequence type 1 (ST1) colony forming units per milliliter (CFU; n = 48, 105, 106, 107, 108, and 109 CFU/ml). Second, mice were inoculated with 108 CFU/ml ST1 and sacrificed at 6 h and 24 h (n = 12/group). Outcome parameters were clinical score, CFUs, cyto- and chemokine levels, and brain histopathology. Third, 84 mice were inoculated (109 CFU/ml ST1) to determine optimal antibiotic treatment with different doses of amoxicillin and gentamicin. Fourth, mice were inoculated with 109 CFU/ml ST1, treated with amoxicillin, and sacrificed at 16 h and 24 h (n = 12/group) for outcome assessment. Finally, time point experiments were repeated with ST6 (n = 24/group). RESULTS: Median survival time for inoculation with 108 and 109 CFU/ml ST1 was 46 h and 40 h; lower doses of bacteria led to minimal clinical signs of disease. Brain levels of IL-6, IL-17A, and IFN-γ were elevated at 24 h, and IL-1ß, IL-6, IL-10, IFN-γ, and TNF-α were elevated in blood at 6 h and 24 h. Histopathology showed increased meningeal infiltration, vascular inflammation of meningeal vessels, hemorrhages, and ventriculitis. In the treatment model, brain levels of IL-6 and IL-17A and blood levels of IL-6 and IFN-γ were elevated. Compared to ST6, infection with ST1 led initially to higher levels of IL-1ß and TNF-α in blood and more profound neuropathological damage. At 16 h post inoculation, IL-1ß, IL-10, and TNF-α in blood and IL-6, IL17A, TNF-α, and IFN-γ levels in brain were higher in ST1 compared to ST6 without differences in CFUs between STs. At 24 h, neuropathology score was higher in ST1 compared to ST6 (p = 0.002) infected mice. CONCLUSIONS: We developed and validated a murine model of listerial meningitis. ST1-infected mice had a more severe inflammatory response and brain damage as compared to ST6-infected mice.

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.

[Listeriosis of the central nervous system: epidemiological and diagnostic aspects--own observations]. / Listerioza osrodkowego ukladu nerwowego: aspekty epidemiologiczne i diagnostyczne--obserwacje wlasne.

UNLABELLED: The aim of the study was to evaluate clinical and laboratory findings and predisposing factors for Listeria monocytogenes (Lm) meningitis. METHODS: 17 intensive care unit patients (12 M, 5 F), aged 54.4 +/- 15.3 yrs, were studied. CNS listeriosis was confirmed by culture of cerebrospinal fluid (CSF) or CSF pleocytosis coupled with Lm bacteriemia. RESULTS: The frequency of central nervous system (CNS) listeriosis among patients with bacterial meningitis was 5.5%. Meningeal signs were present in all patients. 15 patients had impaired level of consciousness. Possible predisposing factors occurred in 15 patients. The average CSF white blood cell count was 1034 +/- 1064 cells/microl. CONCLUSION: Symptoms and signs of patients with CNS listeriosis were not different from those usually found in other bacterial meningitis. A trend toward fewer WBC in CSF was revealed. Most patients with Lm meningitis were immunocompromised.

Listeria monocytogenes meningitis associated with rhabdomyolysis and acute renal failure.

INTRODUCTION: Numerous systemic infections are capable of inducing myositis and rhabdomyolysis. Clinical course of the disease is in the great majority of patients benign and without development of renal dysfunction. However, serious consequences are possible if acute renal failure (ARF) occurs, especially in critically ill patients. METHODS: Patient with Listeria monocytogenes meningitis associated with rhabdomyolysis and acute non-oliguric ARF is presented. RESULTS: Sixty-nine-year-old white male was admitted to our intensive care unit because of listerial meningitis. The course of the disease was complicated with rhabdomyolysis and non-oliguric ARF. After antimicrobial treatment with parenteral trimethoprim-sulfamethoxazole and 4 days of continuous veno-venous hemodiafiltration (CVVHDF) the patient recovered. CONCLUSION: We report a case of listerial meningitis complicated with non-oliguric ARF. Rhabdomyolysis should be considered in all patients with infection and increased CK, especially if consciousness is impaired is altered. Furthermore, despite the normal diuresis ARF could be present and result in adverse consequences. We infer that timely diagnosis and treatment should improve the outcome of infection-induced rhabdomyolysis and could prevent a proportion of associated ARF.

Brainstem and cranial nerve abnormalities: listeriosis, otitis media/interna, and pituitary abscess syndrome.

This article reviews three disorders associated with multiple asymmetric cranial nerve deficits in ruminants: encephalitic listeriosis,otitis media/interna, and pituitary abscess syndrome. Emphasis is placed on encephalitic listeriosis, an infectious disease of the brainstem and cranial nerves caused by Listeria monocytogenes. The epidemiology, pathophysiology, clinical manifestations, diagnosis,and treatment of encephalitic listeriosis are reviewed, and differences between cattle and small ruminants are noted. Physical and neurologic examination findings that distinguish otitis media/interna and pituitary abscess syndrome from encephalitic listeriosis are highlighted.

Listeria and atypical presentations of Listeria in the central nervous system.

Listeria monocytogenes infection of the central nervous system is often not recognized and treated appropriately in the crucial early stages of the disease. Most consider patients with underlying disease or immunocompromised states to be at risk, although healthy individuals may present with a neurologic syndrome caused by L. monocytogenes. Earlier suspicion and treatment remains our best means of reducing the morbidity and high mortality rate of this treatable disease. In addition to meningitis and meningoencephalitis, infection of the brainstem (rhomboencephalitis) is challenging to recognize and therefore initiate appropriate early therapy. Cerebritis and abscess can also occur. Furthermore, empirical therapy for meningitis or the other manifestations of nervous system involvement is often inadequate. This review addresses the clinical microbiology, pathogenesis, spectrum of neurological involvement, and treatment of central nervous system infection related to L. monocytogenes.

Central nervous system infection with Listeria monocytogenes. 33 years' experience at a general hospital and review of 776 episodes from the literature.

We reviewed 776 previously reported and 44 new cases of CNS listeriosis outside of pregnancy and the neonatal period, and evaluated the epidemiologic, diagnostic, and therapeutic characteristics of this infection. Among patients with Listeria meningitis/meningoencephalitis, hematologic malignancy and kidney transplantation were the leading predisposing factors, but 36% of patients had no underlying diseases recognized. The infection occurred throughout life, with a higher incidence before the age of 3 and after the age of 45-50 years. Fever, altered sensorium, and headache were the most common symptoms, but 42% of patients had no meningeal signs on admission. Compared with patients with acute meningitis due to other bacterial pathogens, patients with Listeria infection had a significantly lower incidence of meningeal signs, and the CSF profile was significantly less likely to have a high WBC count or a high protein concentration. Gram stain of CSF was negative in two-thirds of cases of CNS listeriosis. One-third of patients had focal neurologic findings, and approximately one-fourth developed seizures over their course. Mortality was 26% overall, and was higher among patients with seizures and those older than 65 years of age. Relapse occurred in 7% of episodes. Ampicillin for a minimum of 15-21 days (with an aminoglycoside for at least the first 7-10 days) remains the treatment of choice. Cerebritis/abscess due to L. monocytogenes, without meningeal involvement, is less common but may be diagnosed by blood cultures and CNS imaging, or by stereotactic biopsy. Longer antibiotic therapy (at least 5-6 weeks) is needed in the presence of localized CNS involvement.

Listeria meningitis: a case study.

This case illustrates that L monocytogenes should always be considered as a potential cause of clinical meningitis, especially in an immunocompromised patient. The incidence of undetected or misdiagnosed Listeria organisms (as revealed in autopsies) is high enough that extra caution should be taken to ensure that an organism is not simply disregarded as a contaminant.

Listerial meningitis. Which patients are vulnerable?

The physician's index of suspicion for infection with Listeria monocytogenes should be elevated if a patient presents with symptoms of meningitis and has impaired cell-mediated immunity. Although diagnosis is aided by detection of an elevated white blood cell count and protein level in the cerebrospinal fluid, it requires isolation of the organism from the cerebrospinal fluid. Appropriate antibiotic treatment leads to recovery in most cases.

Listeria monocytogenes meningitis in adults. Sixteen consecutive cases 1973-1982.

16 adult patients with Listeria monocytogenes meningitis were reviewed to see whether clinical features or initial laboratory findings could discriminate between these patients and patients with purulent meningitis of other causes. Six patients suffered from known predisposing diseases and 4 were alcoholics. The initial clinical picture was indistinguishable from meningitis of other causes. Microscopy of cerebrospinal fluid (CSF) was negative in all cases but 2 where gram-positive rods were seen. CSF cytology and biochemistry could not discriminate from other causes of purulent meningitis although a low leucocyte content and a low percentage of neutrophils were often present. All L. monocytogenes strains isolated were sensitive to ampicillin and aminoglycosides whereas susceptibility to other antibiotics was low or varying. In adult patients suffering from purulent meningitis initial therapy should include ampicillin until an etiological diagnosis is established. The same is true in some cases of febrile encephalopathy with low content of neutrophils in CSF, especially when the glucose content is low.