Listeria Meningitis in Pediatric Patient with Associated Pneumonia Presenting with Refractory Status Epilepticus: Expanding the Clinical Spectrum of an Underrecognized Entity

To the Editors: Listeria monocytogenes is a gram-positive, facultative intracellular bacterium primarily transmitted to humans through the ingestion of contaminated food, particularly unprocessed or inadequately stored food products. It typically affects pregnant women, neonates, the elderly, and immunocompromised individuals.1 However, its occurrence in previously healthy and immunocompetent children raises questions about whether its occurrence in this group is truly rare or underrecognized. While Listeria classically presents with fever and meningeal signs, its association with coexisting pneumonia and rapidly progressing neurological symptoms in children has not been widely documented. Furthermore, its presentation with prolonged refractory status epilepticus as an initial symptom is highly unusual, particularly in an immunocompetent pediatric patient. This case underscores the need for broader recognition of Listeria infections beyond traditionally affected populations, particularly in children presenting with both severe respiratory involvement and extended neurologic symptoms. A fully immunized 5.5-year-old male with a history of a febrile seizure at 9 months of age was brought to the pediatric emergency department after having a generalized tonic-clonic seizure. On admission to the hospital, the patient’s seizure had resolved and his Glasgow Coma Scale score was 15. The patient’s vital signs were heart rate 101 beats per minute, body temperature 38 °C, oxygen saturation 92% on room air and blood pressure 110/60 mmHg. Physical examination revealed no rash, gastrointestinal symptoms, or other systemic findings, however, otoscopic evaluation showed signs of otitis media. Laboratory investigations revealed a white blood cell count of 7530/mm³, with 75.7% neutrophils. The C-reactive protein level was 2.6 mg/dL (normal <0.5 mg/dL). Electrolyte levels, renal function tests, and coagulation parameters were all within normal limits. Initial imaging revealed significant pneumonic infiltrates on the posteroanterior chest radiograph (Fig. 1A,B). However, during his emergency department stay, the patient developed a sudden deterioration in consciousness, followed by recurrent generalized tonic-clonic seizures. The seizures lasted longer than 5 minutes, fulfilling the criteria for status epilepticus. Although multiple antiepileptic treatments were administered, seizure activity persisted and his level of consciousness progressively declined. Despite recommendations from the neurology department, seizures remained uncontrolled, and fever persisted. Due to ongoing seizure activity and fever, a lumbar puncture could not be performed at that time. Because of the inability to control seizures and concerns about airway protection, the patient was intubated and transferred to the intensive care unit. Given the persistence of epileptic episodes, a cranial CT scan was performed, followed by magnetic resonance imaging when the patient’s clinical condition remained unstable. However, no additional pathological findings were detected. Considering the patient’s history of otitis media and physical examination findings, empirical broad-spectrum antimicrobial therapy, including vancomycin (15 mg/kg/day in 4 doses), ceftriaxone (100 mg/kg/day in 2 doses) and acyclovir (30 mg/kg/day in 3 doses) were initiated at meningitis doses to cover possible pathogens. However, by the third day of treatment, fever persisted, and pneumonia developed. Raising concerns about alternative pathogens and the need for broader pulmonary coverage, ceftriaxone was discontinued and levofloxacin and amikacin were added. By the end of the third day, seizure activity had subsided, allowing for a lumbar puncture and cerebrospinal fluid (CSF) analysis. CSF findings revealed 6 leukocytes/mm³, CSF glucose level of 70 mg/dL, simultaneous blood glucose level of 129 mg/dL and bos protein levels of 19.3 mg/dL.FIGURE 1.: A: Initial chest radiograph on admission, demonstrating significant pneumonic infiltrates. B: Follow-up chest radiograph showing progression of pneumonia despite initial broad-spectrum antibiotic therapy.Although the CSF culture remained sterile, the meningitis PCR detected L. monocytogenes, as reported by the microbiology laboratory. Based on this finding, the antimicrobial regimen was adjusted by discontinuing levofloxacin and acyclovir. The patient’s final targeted treatment course continued with sulbactam ampicillin (200 mg/kg/day in 4 doses) vancomycin (15 mg/kg/day in 4 doses), and amikacin (30 mg/kg/day in 2 doses). During follow-up, seizure activity and fever progressively declined and both clinical and laboratory findings stabilized. As a result, the patient was successfully extubated. With an improved level of consciousness and stable general condition, he was transferred to the pediatric infectious diseases ward for continued antiepileptic therapy and targeted antibiotic treatment for L. monocytogenes. No clinical deterioration or recurrent fever episodes were observed during hospitalization. With the resolution of pneumonia and improvement in the patient’s overall condition, vancomycin and amikacin were continued for a total of 10 days. The antibiotic regimen was completed over a total of 21 days, with the patient remaining in good general condition and without any neurologic sequelae. Immunological screening, including an evaluation of total and subpopulations of T cells, immunoglobulin levels, IgG subclasses and complement function was within normal limits. The HIV test was negative, and no iron overload was detected in laboratory tests. Audiologic evaluation revealed normal hearing function. At a follow-up visit in the outpatient clinic, the patient’s clinical status was normal, with no signs of complications. Neurological complications due to L. monocytogenes infection in immunocompetent children are rarely observed; however, the disease can progress rapidly. Severe central nervous system-related symptoms have been reported in several publications, with L. monocytogenes being frequently implicated as a causative pathogen in hydrocephalus, ventriculitis, and the need for external ventricular drainage.2,3 Additionally, abducens nerve palsy and nystagmus have been described as initial neurological manifestations in some cases.2,4 However, in our case, despite the presence of refractory status epilepticus with seizure activity persisting for approximately 3 days, there was no development of hydrocephalus, ventriculitis, or the need for external ventricular drainage, distinguishing it from previously reported cases. Instead, pneumonia was observed as a coexisting condition, an association that has not been widely documented in non-neonatal age groups with Listeria meningitis. Early diagnosis and appropriate treatment are crucial for achieving optimal outcomes. However, therapy may be delayed as initial empirical treatment with extended-spectrum cephalosporins is ineffective against L. Monocytogenes. This case highlights the potential variability in clinical presentation and underscores the importance of considering L. monocytogenes in pediatric patients presenting with both pneumonia and meningitis, particularly when there is an inadequate response to standard empiric therapy. The clinical presentation of Listeria meningitis is often nonspecific and resembles other bacterial or viral meningitis cases. Reported signs and symptoms include fever, headache, vomiting, altered mental status, and diarrhea, as observed in previous cases. The age at presentation ranged from 7 months to 10 years. Most children, including our patient, presented with leukocytosis with neutrophilia and elevated C-reactive protein levels. Lumbar puncture remains essential for diagnosis. In most cases, CSF analysis reveals pleocytosis with neutrophil predominance, reduced glucose concentration, and elevated protein levels. However, in our case, CSF analysis showed only mild pleocytosis, which contrasts with previous reports describing significant pleocytosis in Listeria meningitis cases that were fatal or developed complications.5 Given that our patient exhibited a more favorable neurological outcome without complications such as hydrocephalus or ventriculitis, this raises the question of whether lower CSF pleocytosis may be associated with a reduced risk of severe neurological sequelae. Further studies are needed to determine whether pleocytosis levels could serve as a prognostic marker for L. monocytogenes meningoencephalitis in pediatric patients. Initial CSF Gram staining and culture were negative in several previously reported cases, suggesting that reliance solely on conventional microbiological methods may lead to delayed diagnosis. Repetition of the CSF analysis is therefore advised in cases of severe meningoencephalitis that do not improve with first-line antibiotic treatment when no specific organism is identified on initial evaluation.6 Despite initial broad-spectrum antimicrobial therapy, including ceftriaxone and vancomycin, the patient’s cultures remained negative, while pneumonia and seizures persisted. Following modifications in the antibiotic regimen, L. monocytogenes was not detected in cultures, but real-time polymerase chain reaction (RT-PCR) confirmed its presence, leading to the initiation of targeted therapy. The absence of bacterial growth in cultures may be attributed to multiple factors, including the in-vitro efficacy of vancomycin against L. monocytogenes, prior antibiotic exposure, or the inherent difficulty in isolating L. monocytogenes using standard culture techniques. L. monocytogenes is a slow-growing facultative intracellular pathogen that may not always be detected in routine cultures. Furthermore, specialized culture techniques are often required for successful isolation, which are not routinely performed in all laboratories.7 These findings emphasize the critical role of molecular diagnostics, particularly RT-PCR, in the early and accurate identification of L. monocytogenes, especially in cases where conventional microbiological methods fail. Upon isolation of L. monocytogenes from the CSF, the treatment regimen should be adjusted to include ampicillin, either as monotherapy or in combination with an aminoglycoside such as gentamicin or amikacin.8 Although only 1 in-vitro study has demonstrated the synergistic effect of ampicillin and amikacin,8 this combination remains the preferred treatment against L. monocytogenes. In our case, ampicillin was added to the treatment upon PCR confirmation of L. monocytogenes, in line with current treatment guidelines. The treatment duration varied from 10 days to a maximum of 8 weeks, depending on the severity of the case. After a total of 21 days of ampicillin and 10 days of amikacin treatment, the patient was discharged without any sequelae. As L. monocytogenes mainly affects immunocompromised hosts, an immunological evaluation could be useful. Underlying causes of immunosuppression, such as prolonged or inappropriate corticosteroid treatment, should be excluded. Finally, blood iron levels should be checked, as iron overload could predispose to Listeria meningitis.9 L. monocytogenes is a rare cause of meningoencephalitis, especially coexisting with pneumonia presentation in non-neonatal, previously healthy, immunocompetent children. However, its clinical presentation is like that of other viral or bacterial central nervous system infections, and its course can be rapid and aggressive. Physicians should therefore always consider L. monocytogenes as a possible etiologic agent of meningoencephalitis, especially in cases that are unresponsive to empiric first-line antibiotic treatment and when gram-positive bacilli are observed in the CSF. Furthermore, although the patient experienced prolonged status epilepticus for three days, recovery occurred without any neurological sequelae. The relatively lower pleocytosis level compared with previously reported severe cases raises the question of whether it might be associated with a milder disease course. Real-time PCR, as in our case, may be useful for prompt diagnosis, which is essential to enable adequate antibiotic treatment to be started with ampicillin alone or in combination with an aminoglycoside.