Treatment of Listeria monocytogenes Rhombencephalitis
High-dose intravenous ampicillin 2 g every 4 hours PLUS gentamicin for synergistic bactericidal effect should be administered immediately for a minimum of 21 days in all cases of Listeria rhombencephalitis. 1, 2
Definitive Treatment Regimen
First-line therapy:
- Ampicillin 2 g IV every 4 hours (or amoxicillin 2 g IV every 4 hours) as the cornerstone agent 1, 3
- PLUS Gentamicin 4 mg/kg IV every 24 hours for synergistic bactericidal activity, which is particularly critical in CNS infections 4, 1, 5
- Duration: 21 days minimum for all CNS/rhombencephalitis presentations 1, 2
The combination of ampicillin plus gentamicin demonstrates in vitro synergism and bactericidal effects against Listeria monocytogenes, whereas either agent alone is only bacteriostatic. 5 This synergy is especially desirable in immunocompromised patients and those with CNS involvement. 5
Severe Penicillin Allergy Alternatives
For patients with documented severe penicillin allergy (anaphylaxis, Stevens-Johnson syndrome):
- Trimethoprim-sulfamethoxazole (TMP-SMX) 10-20 mg/kg/day (based on trimethoprim component) divided into 4 doses is the preferred alternative 4, 1, 6
- Meropenem is also an acceptable alternative for penicillin-allergic patients 1
- Linezolid has been used successfully in case reports of Listeria rhombencephalitis, though clinical experience is limited 7
Critical caveat: Erythromycin and other macrolides are antagonistic when combined with penicillins or gentamicin and should be avoided. 8 Fluoroquinolones are not reliably active against Listeria. 4
Critical Pitfall: Cephalosporin Resistance
Listeria monocytogenes is intrinsically resistant to ALL cephalosporins, including third-generation agents like ceftriaxone and cefotaxime. 1, 3, 2 This is a common and potentially fatal error, as rhombencephalitis can initially mimic facial neuritis or other cranial neuropathies and may be empirically treated with cephalosporin-based meningitis regimens. 9
- Patients whose conditions do not improve with cephalosporin administration should prompt immediate consideration of Listeria and addition of ampicillin 9
- Never use cephalosporin monotherapy when Listeria is a possible pathogen 1, 3
Adjunctive Therapy Considerations
Discontinue dexamethasone immediately if Listeria is identified or suspected, as adjunctive corticosteroids have been linked to increased mortality in neurolisteriosis. 2 This is particularly important because rhombencephalitis may initially be misdiagnosed as facial neuritis and treated with steroids, which can accelerate clinical deterioration. 9
High-Risk Populations Requiring Empiric Listeria Coverage
Ampicillin should be added empirically to standard meningitis regimens in:
- Adults >50 years of age 1, 3, 2
- Pregnant women 1, 3
- Immunocompromised patients (malignancy, HIV, transplant recipients, those on immunosuppressive therapy including anti-TNF agents) 4, 1, 3
- Patients with diabetes mellitus or chronic liver disease 1, 3
Among immunocompromised patients, Listeria accounts for approximately 20% of meningitis cases in those on immunosuppressive medication and is the second most common bacterial cause of infection after Streptococcus pneumoniae in cancer patients. 3
Monitoring and Clinical Course
- Rhombencephalitis develops rapidly and can progress from subtle cranial nerve findings to respiratory failure requiring mechanical ventilation 9
- Brain MRI typically reveals multiple ring-enhanced foci in the brainstem 9
- Blood cultures and CSF analysis (including high-throughput genome sequencing if available) should be obtained, but treatment must not be delayed for diagnostic procedures 2, 9
- Patients may require prolonged intensive care and rehabilitation; recovery can take months even with appropriate therapy 9