Meningitis por Listeria: serie de casos en un hospital de tercer nivel y utilidad de las nuevas técnicas de diagnóstico microbiológico / Listeria meningitis: case series in a tertiary level hospital and the usefulness of new microbiological diagnostic techniques

Introducción: La meningitis por Listeria monocytogenes (MLM) es una entidad grave con complicaciones a corto plazo. La reacción de polimerasa en cadena (RPC) puede ayudar a mejorar su diagnóstico y pronóstico. Objetivos: Conocer las características de los pacientes diagnosticados de meningitis por L. monocytogenes en los últimos años, a través de diferentes métodos microbiológicos. Pacientes y Métodos: Serie de casos de pacientes adultos ingresados con MLM en el Hospital Clínico San Carlos, Madrid, España, durante doce años (2009-2021). Se describieron variables epidemiológicas, clínicas, microbiológicas, radiológicas y terapéuticas. Resultados: Se registraron doce pacientes con MLM (edad media 67,5 años, 75% varones). En ocho se obtuvo un cultivo positivo a L. monocytogenes. La RPC en líquido cefalorraquídeo (LCR) fue positiva en los dos casos en los que se realizó la prueba. El tratamiento dirigido en todos los casos fue ampicilina durante 21 días. Se registraron complicaciones en un cuarto de los casos. Del total de pacientes uno falleció. Conclusiones: La MLM es una enfermedad poco frecuente y de difícil diagnóstico. En nuestra serie de casos los dos pacientes diagnosticados por RPC tuvieron resultado de cultivo de LCR negativo, y presentaron buena evolución. La determinación de RPC podría permitir diagnosticar un mayor número de casos y con mayor precocidad.

Background: Listeria monocytogenes meningitis (LMM) is a serious entity with short-term complications. Polymerase chain reaction (PCR) can help to improve its diagnosis and prognosis. Aim: To know the characteristics of patients diagnosed with meningitis by L. monocytogenes in recent years, through different microbiological methods. Methods: Case series of adult patients admitted with LMM at the Hospital Clínico San Carlos of Madrid, Spain, during twelve years (2009-2021). Epidemiological, clinical, microbiological, radiological and therapeutic variables were described. Results: Twelve patients with LMM were recorded (mean age 67.5 years, 75% male). Eight had a positive culture for L. monocytogenes. cerebrospinal fluid (CSF) PCR was positive in the two cases in which the test was performed. Treatment in all cases was ampicillin for 21 days. Complications were recorded in a quarter of the cases. One patient died. Conclusions: LMM is a rare and difficult to diagnose disease. In our series of cases, the two patients diagnosed by PCR had negative CSF culture results, and presented good evolution. PCR determination could allow a greater number of cases to be diagnosed earlier.

[Listeria meningitis during daratumumab/bortezomib/dexamethasone therapy in a patient with multiple myeloma].

An 88-year-old woman was diagnosed with multiple myeloma received third-line chemotherapy, including DBd (daratumumab [DARA], bortezomib, and dexamethasone [Dex]), and the myeloma was in remission. Sulfamethoxazole/trimethoprim (ST) prophylaxis was discontinued because the dose of Dex was reduced to 20 mg every 4 weeks after 21 cycles of DBd. After 28 cycles of DBd, altered consciousness with fever ensued, and she was referred to the emergency department where Listeria monocytogenes (LM) meningitis was diagnosed. CD38 inactivation is associated with increased LM susceptibility. In patients on Dara-based chemotherapy, antibiotic prophylaxis should be considered using ST, which has activity against Listeria.

[Post colonoscopic Listeria monocytogenes meningitis in a patient with multiple myeloma during daratumumab-based therapy].

A 69-year-old man with an unremarkable medical history presented with asymptomatic pancytopenia and diagnosed with Bence Jones protein-λ multiple myeloma (MM). Despite treatment with various chemotherapeutic regimens, myelosuppressive neutropenia occurred after each successive course; therefore, the treatment was determined to be ineffective and was discontinued. Consequently, one year after the diagnosis, a daratumumab-based therapy was initiated, and the MM was stabilized without clinical or laboratory evidences of myelosuppression. However, 18 months after the daratumumab induction, the patient developed hematochezia. Following an unremarkable lower gastrointestinal endoscopy, he presented fever and disturbed consciousness. Serum laboratory results showed liver dysfunction, and Listeria monocytogenes meningitis was diagnosed by cerebrospinal fluid examination. Empiric antibacterial treatment was administered for 3 weeks, which resolved the symptoms with no permanent neurological deficit.Daratumumab, a CD38 monoclonal antibodies, binds to expressed CD38 on myeloma cells and has an anti-myeloma cytotoxic effect but also binds to CD38 on activated macrophages. Additionally, activated macrophages play an important role in the immune defense of Listeria monocytogenes. Furthermore, inactivation of macrophages may increase the susceptibility to Listeria infection. Therefore, the possibility of infections such as Listeria meningitis should be considered in patients with MM receiving daratumumab-based therapy.

Acquired immunodeficiency associated with thymoma: a case report.

BACKGROUND: Acquired immunodeficiency associated with thymoma is a rare disorder. Here we reported a case of acquired immunodeficiency with thymoma, with an unusual pattern of low CD4+ count with normal gammaglobulin levels. CASE PRESENTATION: A 70-year-old man presented to the emergency room of our hospital with a high-grade fever, headache, and nausea. He had a five-year history of unresectable thymoma treatment, including several cytotoxic regimens. He had received thoracic palliative radiotherapy 2 months prior to the emergent visit. During the previous month, he had experienced multiple febrile episodes, dry cough, fatigue, weight loss, and watery diarrhea. Upon admission, he had a high-grade fever, nausea, and immobility. Physical examination revealed indistinct consciousness, neck stiffness, and oropharyngeal candidiasis. Both cerebrospinal fluid and blood cultures yielded multiple short chains of Gram-positive rods later identified as Listeria monocytogenes, so he was diagnosed with Listeria meningitis. Intravenous administration of antibiotics was initiated, and the patient fully recovered and was discharged. Additional examination found normal immunoglobulin levels. Peripheral-blood cell counts revealed low CD4+ cell count (108 CD4+ cells/µl). His CD4+ cell count remained low after discharge. CONCLUSIONS: Our findings suggest that physicians need to be aware of severe infections due to immunodeficiency with thymoma.

Reasonable drug analysis of Listeria monocytogenes meningitis related to mantle cell lymphoma.

We report a case of Listeria meningitis related to mantle cell lymphoma. A clinical pharmacist adjusted repeatedly the patient's anti-infective therapeutic regimen by analyzing the pharmacologic and pharmacokinetic characteristics of antibacterial drugs (such as cefotaxime, meropenem, etc.) due to the patient's repeated fever during hospitalization. To the best of our knowledge, this is the first case of Listeria meningitis related to mantle cell lymphoma treated successfully with meropenem reported in China. This case aims to optimize the anti-infection treatment regimen of Listeria meningitis and to provide a reference for clinicians and clinical pharmacists to use drugs rationally.

Epidemiology and treatment of the commonest form of listeriosis: meningitis and bacteraemia.

Listeria monocytogenes is a Gram-positive bacillus and facultative intracellular bacterium whose transmission occurs mainly through the consumption of contaminated food. Listeriosis has an incidence estimated at around three-six cases per million per year and the most common forms of the infection are neurolisteriosis, bacteraemia, and maternal-neonatal infection. Those affected by listeriosis are at the extremes age of the life or report specific risk factors, such as malignancies, causing a defect of cellular immunity. Patients with L. monocytogenes meningitis present with signs and symptoms similar to those reported in the general population with community-acquired bacterial meningitis, but can experience a longer prodromal phase. Instead, patients with bacteraemia present generally with a febrile illness without focal symptoms, or with influenza-like symptoms and diarrhoea. These aspecific findings make the diagnosis difficult in the population of patients at the highest risk such as cirrhotics or those receiving chemotherapy. Mortality rate is estimated around 20% with a significant increase among those reporting a delay in diagnosis and treatment and in those with severe comorbidity. A number of antibiotics have been demonstrated to be active against L. monocytogenes, but penicillin, amoxicillin, and ampicillin are those used with the highest frequency and suggested by current guidelines and expert opinions. These antibiotics bind to PBP-3 with high affinity and are stored in the cytosol when taken up by cells. Although amoxicillin appears to have a better activity than ampicillin on the basis of in vitro studies, ampicillin is currently the drug of choice for the treatment of listeriosis. Cotrimoxazole could be administered as an alternative treatment; its use is associated with a favourable outcome probably due to the favourable penetration with brain. Quinolones have an excellent tissue and cell penetration and are rapidly bactericidal, but their clinical activity is not as high as we can predict on the basis of experimental model. Linezolid offers a number of advantages in the empiric treatment of meningitis due to its favourable penetration of CSF and the absence of bacteriolytic effect on S. pneumoniae as confirmed by a number of case-series highlighting its use as rescue therapy of pneumococcal meningitis, but data are currently limited particularly if we consider neurolisteriosis. Combination therapies have been proposed to enhance the activity of penicillins against Listeria in an attempt to achieve complete killing and decrease mortality. Steroids use is ineffective.

Meningitis por Listeria monocytogenes en niñas inmunocompetentes: queso no pasteurizado como probable causa de infección / Listeria monocytogenes meningitis in immunocompetent children: unpasteurized cheese likely cause of infection

Listeria meningoencephalitis is a rare condition, occurring mainly in immunocompromised patients. We present two cases of Listeria monocytogenes meningoencephalitis in immunocompetent children, with successful treatment with betalactam/aminoglycoside combination. Unpasteurized cheese was postulated as the source of infection.

La meningoencefalitis por Listeria spp. es una infección infrecuente, principalmente en pacientes con algún tipo de inmunosupresión. Presentamos dos casos clínicos de meningitis por Listeria monocytogenes en niñas inmunocompetentes con tratamiento exitoso con β lactámicos combinados con aminoglucósidos; se identificó la ingesta de queso no pasteurizado como probable fuente de infección.

Listeria monocytogenes meningitis in an immunocompromised patient.

This report describes a case of meningitis caused by Listeria monocytogenes in a stem cell transplant recipient on immunosuppressive therapy for cutaneous chronic graft-versus host disease. A 59-year-old woman had undergone allogeneic stem cell transplantation (from a matched unrelated donor) 13 months previously for chronic lymphocytic leukemia. She was on regular hematologic follow-up. Though her previous malignancy has been in remission, she was immunosuppressed due to the pharmacological treatment. We describe a meningitis caused by a typical food-borne pathogen, dangerous in patients with impaired cell-mediated immunity. Moreover the bacterium had a multidrug resistance, a rare characteristic in clinical listeriosis. Rapid diagnosis and treatment are key factors in these cases. We chose ampicillin and rifampicin that allowed a complete resolution of the clinical manifestations.

Listeria monocytogenes brain abscess: two cases and review of the literature.

Listeria monocytogenes is a gram-positive bacillus that exhibits predilection to infect the central nervous system in immunocompromised individuals; the most common manifestations are meningitis and rhombencephalitis. Listerial brain abscesses are rare. We report here two brain abscess cases caused by L. monocytogenes in patients receiving immunosuppressive agents. The first patient presented with left hemiparesis mimicking stroke and the second patient presented with neurological symptoms without fever, which was indistinguishable from brain tumor. In both cases, magnetic resonance spectroscopy (MRS) was performed to differentiate infectious processes from other causes. Diagnosis was made with a positive blood culture in both cases. Listerial DNA was detected in the pus aspirated from the abscess in the first case. Both patients were successfully treated with intravenous ampicillin followed by oral amoxicillin. MRS was useful in differentiating infectious processes from non-infectious causes.

[Meningitis due to Listeria monocytogenes in adults]. / Meningitis por Listeria monocytogenes en adultos.

INTRODUCTION: Listeria monocytogenes is the third most common cause of community-acquired bacterial meningitis in adults. AIMS: To describe the characteristics of meningitis caused by Listeria (LM) in adults and to compare them with those of meningitis due to other causations (nLM). PATIENTS AND METHODS: A retrospective analysis of a series of hospital cases was conducted, including patients aged between ≥ 14 years diagnosed with LM in a referral hospital between 1982 and 2011. RESULTS: The study involves 16 cases of LM, 12.1% of the cases of community-acquired meningitis with an identified aetiology. Predisposing factors were age (mean of 65 versus 52 years; p = 0.019) and immunosuppression/comorbidity (62.5% versus 3.4%; p < 0.001), treatment with corticoids (37.5%) and chronic liver disease (25%) being the most frequent. The classical triads of acute bacterial meningitis, clinical features and analysis of the cerebrospinal fluid (CSF) were observed in 50 and 75% of the cases, respectively. Patients with LM presented lower leukocyte counts in CSF, a lower percentage of neutrophils, a greater frequency of lymphocytic pleocytosis and a lower frequency of Gram stain positive than those with nLM. The mortality rate was 12.5%, similar to that of patients with nLM. CONCLUSIONS: LM mainly affects patients who are immunosuppressed or with comorbidity, as well as elderly patients, although it may occur in the absence of risk factors. Clinically it does not differ from other causes of meningitis, but the initial CSF study may suggest it. Its mortality rate is similar to that of meningitis due to other aetiologies.

Listeria monocytogenes meningitis in an immunocompetent adult: a case report / Listeria monocytogenes meningite em um adulto imunocompetente: relato de caso

Listeria monocytogenes (L. monocytogenes) is an uncommon cause of bacterial meningitis in immunocompetent adults. Patients with immunosuppression are at increased risk of developing serious invasive diseases, particularly meningitis. We describe a case of meningitis caused by L. monocytogenes in an immunocompetent and previously healthy 34-year-old adult. The patient received treatment with intravenous ampicillin plus amikacin and made a full recovery. L. monocytogenes should be suspected in immunocompetent adults with bacterial meningitis who fail to respond to empirical antibiotic treatment.

Listeria monocytogenes (L. monocytogenes) é uma causa rara de meningite bacteriana em adultos imunocompetentes. Pacientes com imunossupressão têm maior risco de desenvolver graves doenças invasivas, especialmente a meningite. Descrevemos um caso de meningite por L. monocytogenes em um adulto imunocompetente e previamente sadio com idade de 34 anos. O paciente recebeu tratamento com ampicilina intravenosa mais amicacina e fez uma recuperação completa. L. monocytogenes deve ser suspeitada em imunocompetentes adultos com meningite bacteriana que não respondem ao tratamento antibiótico empírico.

Listeria monocytogenes meningitis in two immunocompetent children.

Listeria monocytogenes is an uncommon cause of bacterial meningitis beyond the neonatal period. Patients with immunosuppression or neoplastic disease are at increased risk of developing serious invasive disease, particularly meningitis. L. monocytogenes meningitis in two previously healthy, immunocompetent children aged 7 years and 18 months is described. One of them was successfully treated with ampicillin and amikacin. In the other there was resistance to ampicillin, and meropenem, vancomycin and amikacin were given. One patient developed unilateral abducens paralysis and inappropriate antidiuretic hormone secretion. L. monocytogenes should be suspected in children with bacterial meningitis who fail to respond to empirical antibiotic therapy.

Neurolisteriosis: descripción de siete casos / Neurolisteriosis: description of seven cases

Listeria Monocytogenes is a gram-positive Bacillus that affects immunocompromised patients, newborn, pregnant women and persons over 65 years. Infection is acquired through contaminated food. The Bacillus has predilection for the central nervous system. Its presents most commonly as an acute meningitis, it also presents as a chronic meningitis, cerebritis, rhomboencephalitis, brain and spinal abscess. Diagnosis for L. monocytogenes is made through positive cultures in blood and cerebrospinal fluid (CSF). Magnetic Resonance (MR) also helps to in the diagnosis of neurolisteriosis lesions. We described seven cases with L. Monocytogenes infection during 2007 and 2008, with four cases over the aged of 65 years old. Five presented acute meningitis; two rhomboencephalitis and one patient had meningoencephalitis. Six cases showed inflammatory CSF with pleocytosis with polymorphonuclear prevail and normal glycorrachia. MR showed inflammatory findings in five patients and focal brainstem lesions in two cases, one had acute hydrocephalus due arachnoiditis. Five patients improve clinically and two fatal cases were described. Listeriosis is the third cause of meningitis and should be consider in the differential diagnosis of meningitis with clear fluid, especially with pleocytosis and normal glycorrachia. Other clues of the diagnosis are dizziness with or without nystagmus and brainstem compromise. Arachnoiditis should be avoided with steroidal use. The diagnostic imaging test of choice for brain stem compromise is MR.

La Listeria Monocytogenes es un bacilo Gram-positivo que afecta a pacientes inmunocomprometidos, a niños, embarazadas y personas mayores de 65 años. El modo de adquirirla es la ingestión de alimentos contaminados. El bacilo tiene predilección por el sistema nervioso central, donde su expresión más frecuente es la meningitis aguda, también puede presentarse como meningitis crónica, cerebritis, rombencefalitis, abscesos cerebrales y espinales. El cultivos positivos de L. monocytogenes en muestras de sangre o líquido cefalorraquídeo, permite confirmar el diagnóstico. La Resonancia Magnética de cerebro también contribuye al diagnóstico de las lesiones por neurolisteriosis. Se analizan siete casos de neurolisteriosis ocurridos los a±os 2007 y 2008, entre ellos cuatro pacientes mayores de 65 años. La meningitis aguda fue la forma de presentación en cinco de ellos, dos evolucionaron como rombencefalitis y uno como meningoencefalitis. El LCR fue inflamatorio en seis de los pacientes, con pleocitosis depredominio polinuclear, pero glucorraquia normal. La RM mostró imágenes de aspecto inflamatorio en cinco de los enfermos, dos de ellos tenían lesiones focales del tronco cerebral, uno hizo un hidrocéfalo agudo por aracnoiditis. Cinco pacientes presentaron una evolución clínica favorable y dos fallecieron. Siendo la listeriosis la tercera causa etiológica de meningitis, debe ser considerada en el diagnóstico diferencial de meningitis a líquido claro, especialmente en LCR con abundantes polinucleares y glucosa en rangos normales. Otras claves son la sensación vertiginosa con o sin nistagmus y el compromiso de nervios craneales de origen protuberancial. Debe prevenirse las aracnoiditis con el uso precoz de corticoides. Es obligatorio el estudio con RM en toda sospecha de neurolisteriosis.

[Neurolisteriosis with acute myelitis]. / Akute Myelitis bei Neurolisteriose.

Listeriosis is a bacterial infection with Listeria monocytogenes mostly affecting immunocompromised patients. In every fourth case, the CNS is involved, usually as meningoencephalitis. This case report of an immunocompetent woman represents the first one of neurolisteriosis initially presenting as cervical myelitis and progressing to supratentorial areas of the brain. Diagnosis was based on universal polymerase chain reaction from a cortical brain biopsy, followed by sequencing of the amplified rDNA gene. Under antibiotic treatment with gentamycin and ampicillin, the patient slowly recovered and has been improving ever since.

Successful treatment of disseminated cerebritis complicating methicillin-resistant Staphylococcus aureus Endocarditis unresponsive to vancomycin therapy with linezolid.

A unique case of community acquired methicillin resistant Staphylococcus aureus (MRSA) sepsis, with endocardial and cerebral metastatic seeding, caused by a strain representative of the Italian clone, is described. The patient was a 47-y-old man without apparent risk factors for endocarditis and for MRSA infection who developed coma with multiple cerebritis lesions under vancomycin plus amikacin therapy. He was eventually cured with the addition of linezolid to the initial antimicrobial regimen. This observation seems to confirm previous reports of the efficacy of linezolid for the treatment of central nervous system infections caused by multidrug resistant Gram-positive bacteria. To our knowledge, this is the first report of MRSA disseminated cerebritis, a nearly always fatal disease, cured with this oxazolidinone drug. The increase in community acquired MRSA may have some impact on empirical treatment of serious infections caused by this organism.

Listeria meningitis associated with infliximab.

OBJECTIVE: To report a case of Listeria monocytogenes meningitis in a 73-year-old man receiving infliximab for rheumatoid arthritis. CASE SUMMARY: A 73-year-old white man taking infliximab for rheumatoid arthritis developed listeria meningitis following his second dose. He was receiving other immunosuppressants; however, these remained constant immediately prior to the infection. Diagnosis was confirmed with L. monocytogenes isolated in the cerebrospinal fluid. The patient received 21 days of antibiotic therapy and recovered without any complications. DISCUSSION: L. monocytogenes is a gram-positive, non-spore-forming rod that has been associated with the ingestion of undercooked foods. This organism can cause sepsis or meningitis; however, immunocompromised patients, elderly patients, pregnant women, and neonates appear to be at greater risk for this type of infection. Tumor-necrosis factor-alpha (TNF-alpha) plays an important role in resistance to this type of infection, and listeria infections have been reported in 26 patients receiving TNF-alpha inhibitors. In our patient, the listeria infection occurred following his second course of infliximab, which provides a temporal relationship between the listeria infection and infliximab. However, his underlying rheumatoid arthritis and chronic steroid therapy would also increase his risk for a listeria infection. CONCLUSIONS: The listeria infection in our patient was a possible adverse event of infliximab according to the Naranjo probability scale. Because the majority of listeria infections occur in patients who are immunosuppressed, it would be reasonable to provide education for healthcare professionals on preventing these infections in all patients receiving immunosuppressants, including anti-TNF-alpha therapy. Those at risk due to their underlying health conditions should also be monitored closely.

[Neural listeriosis presenting as leptomeningitis: a case report]. / Neurolisterioza przebiegajaca pod postacia ropnego zapalenia opon mózgowo-rdzeniowych--przypadek kliniczny.

The Listeria monocytogenes infection is rare and difficult to diagnosis. However, it is associated with a high mortality in adults. A case is presented of a 78-year-old woman with an immunological deficit following viral infection (herpes zoster).