Can linezolid be used as an alternative for Listeria meningitis?

Comment by InpharmD Researcher

Data to support the use of linezolid as an alternative treatment option for Listeria meningitis is primarily limited to case reports. Linezolid often results in successful treatment in available reports, but is often combined with other agents such as a carbapenem, ceftriaxone, rifampin, gentamicin, or penicillin. In general, linezolid appears to result in adequate in vitro activity against Listeria monocytogenes and adequate cerebrospinal fluid concentrations, making it a useful alternative in the treatment of Listeria meningitis when allergy to both penicillin and cotrimoxazole is of concern.

Background

A clinical review discussing the treatment of listeriosis, including meningitis and bacteremia, notes that linezolid is an oxazolidinone reporting in vitro activity against Listeria monocytogenes (L. monocytogenes). Linezolid also results in cerebrospinal fluid (CSF) and intracellular concentrations that are adequate for the treatment of neurolisteriosis, as identified by animal models. When allergy to both penicillin and cotrimoxazole became of concern, a linezolid-rifampin combination was successfully administered to a patient with brain abscess sustained by L. monocytogenes without any hematological toxicity after 107 consecutive days of treatment. It is suggested that 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, which has been observed in various case series highlighting its use as rescue therapy of pneumococcal meningitis. Despite the promising use of linezolid in meningitis, a separate review recommends that it not be used for empirical therapy of meningitis/ventriculitis without adequate susceptibility testing. [1], [2]

References:

[1] Pagliano P, Arslan F, Ascione T. Epidemiology and treatment of the commonest form of listeriosis: meningitis and bacteraemia. Infez Med. 2017;25(3):210-216.
[2] Nau R, Djukic M, Spreer A, Ribes S, Eiffert H. Bacterial meningitis: an update of new treatment options. Expert Rev Anti Infect Ther. 2015;13(11):1401-1423. doi:10.1586/14787210.2015.1077700

Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

Can linezolid be used as an alternative for Listeria meningitis?

Level of evidence

D - Case reports or unreliable data  Read more→



Please see Tables 1-5 for your response.


 

Linezolid Activity Against Disseminated Listeria monocytogenes Meningitis and Central Nervous System Abscesses: Focus on Early Drug Myelotoxicity

Design

Case report

Case presentation

A 50-year-old immunocompetent male developed central nervous system (CNS) listeriosis, manifesting as meningitis and multiple brainstem and cerebellar abscesses. The patient initially presented with dizziness, later progressing to signs indicative of bacterial meningitis, including hyperpyrexia, confusion, vomiting, and meningeal irritation. CSF analysis revealed elevated albumin (217 mg/dL), markedly low glucose (4 mg/dL), and moderate pleocytosis (256 cells/μL, 60% neutrophils). Empiric therapy with intravenous ceftriaxone and chloramphenicol was initiated but proved ineffective. Upon identification of Listeria monocytogenes in the CSF, antimicrobial therapy was escalated to high-dose ampicillin (12 g/day) combined with gentamicin (240 mg/day).

Persistent clinical deterioration and neurologic deficits prompted further therapeutic modifications, including the sequential use of intravenous rifampin, cotrimoxazole, and ultimately, linezolid (1,200 mg/day) in combination with meropenem (6 g/day), following MRI-confirmed diagnosis of multiple subtentorial abscesses involving the medulla, pons, and cerebellum. The introduction of linezolid resulted in rapid clinical and biochemical improvement, as evidenced by normalization trends in CSF glucose and albumin, reduction in leukocyte count, resolution of systemic symptoms, and gradual recovery of neurologic function. Notably, linezolid use was complicated by rapid-onset anemia (hemoglobin nadir 7.5 g/dL) requiring two transfusions, with onset occurring as early as day 6 of therapy. This hematologic adverse event necessitated the discontinuation of linezolid after 21 days, after which anemia resolved. The patient was discharged on oral cotrimoxazole and exhibited full neurologic recovery, with MRI confirmation of radiographic resolution of abscesses at one-month follow-up and sustained remission at six months.

Study Author Conclusions

Despite the demonstrated in vitro activity of a broad spectrum of agents, multiple changes of antimicrobial chemotherapy became necessary, until the combination of meropenem and linezolid, which was introduced at the time of the appearance of the most severe neurological complications, and proved very effective, although it was affected by relapsing anemia probably attributable to linezolid use, and requiring transfusion therapy.

 

References:

Manfredi R. Linezolid activity against disseminated Listeria monocytogenes meningitis and central nervous system abscesses: focus on early drug myelotoxicity. Curr Drug Saf. 2007;2(2):141-145. doi:10.2174/157488607780598304

 

Listeria Monocytogenes Meningitis in an Immunocompetent Patient

Design

Case report

Case presentation

A previously healthy 45-year-old man without identifiable immunosuppressive risk factors presented with Listeria monocytogenes (LM) meningitis in the emergency department, along with a four-day history of diplopia, left ocular medial deviation, and ptosis, but without classical features of meningitis such as fever, neck stiffness, or altered mental status. Initial diagnostic evaluations, including head CT and thoracic imaging, were unremarkable. Due to the atypical presentation and absence of overt systemic signs of infection, the early differential diagnosis included cerebral aneurysm and demyelinating disease, prompting magnetic resonance angiography (MRA), which excluded vascular pathology but showed nonspecific periventricular lesions. On day 3 of hospitalization, the patient developed tremors and diaphoresis, prompting a lumbar puncture. CSF analysis revealed a turbid appearance, elevated protein (125 mg/dL), markedly reduced glucose (<20 mg/dL), elevated lactate, and a predominance of neutrophils.

Rare Gram-positive coccobacilli were identified on microscopy, and empirical antimicrobial therapy was initiated with intravenous ceftriaxone, linezolid (substituted for vancomycin due to a formulary shortage), and dexamethasone. CSF cultures later confirmed sensitivity to ampicillin, amoxicillin-clavulanate, erythromycin, linezolid, tetracycline, and vancomycin. Therapy was modified to include ampicillin and vancomycin, leading to full clinical resolution. The patient was discharged on day 21 with a seven-day course of oral ampicillin and demonstrated complete recovery at follow-up.

Study Author Conclusions

We presented this case to raise awareness about LM as a possible cause for bacterial meningitis in immunocompetent patients with uncharacteristic clinical symptoms and to confirm that linezolid is a viable treatment option for patients with LM meningitis leading to favourable outcomes.

 

References:

Magiar O, Vulpie S, Musuroi C, et al. Listeria Monocytogenes Meningitis in an Immunocompetent Patient. Infect Drug Resist. 2022;15:989-994. Published 2022 Mar 10. doi:10.2147/IDR.S351132

 

Listeria monocytogenes rhombencephalitis in a patient with multiple sclerosis during fingolimod therapy

Design

Case report

Case presentation

A 44-year-old woman with a five-year history of multiple sclerosis (MS) initially presented with left-sided hemiparesthesia and hemiparesis. She was diagnosed with MS and began treatment with glatiramer acetate, experiencing only one relapse in the following three years. However, her condition progressively worsened, marked by increased paresthesias, reduced walking capacity, and the onset of urinary incontinence. As a result, her therapy was escalated to fingolimod. In July 2018, she was hospitalized with a two-day history of bilateral leg paresthesias and painful cramps, which was soon followed by fever, headache, and confusion. On examination, she exhibited nuchal rigidity, raising suspicion for meningoencephalitis. A lumbar puncture was not performed due to lack of family consent. Laboratory tests revealed leukocytosis and elevated C-reactive protein levels.

Empirical treatment with imipenem and linezolid was initiated after referral to the Infectious Diseases department. Magnetic resonance imaging imaging showed acute hydrocephalus and a hyperintense lesion in the mesencephalon extending from the tegmentum to the corpus, consistent with acute rhombencephalitis with associated hydrocephalus. She underwent emergency shunt surgery and was intubated. Cerebrospinal fluid (CSF) analysis from the shunt procedure revealed 80 leukocytes, elevated protein, low chloride, and elevated glucose levels. CSF culture confirmed Listeria monocytogenes infection. She was treated with a 21-day course of ampicillin, leading to significant clinical and neurological improvement. Follow-up imaging showed partial resolution of the hydrocephalus. While her level of consciousness improved and she regained the ability to comprehend and perform simple commands, she remained with residual tetraparesis.

Study Author Conclusions

Here, we presented a MS patient who developed L. monocytogenes rhombencephalitis with hydrocephalus during fingolimod treatment. Previously, listeriosis has been reported in MS patients undergoing alemtuzumab therapy and in one patient on dimethyl fumarate. To our knowledge, this is the first reported case of listeriosis in a patient on fingolimod therapy. Clinicians should be aware of listeriosis and implement measures for its prevention.

References:

Tecellioglu M, Kamisli O, Kamisli S, Erdogmus UA, Özcan C. Listeria monocytogenes rhombencephalitis in a patient with multiple sclerosis during fingolimod therapy. Mult Scler Relat Disord. 2019;27:409-411. doi:10.1016/j.msard.2018.11.025

 

Treatment of Brain Abscess Caused by Listeria monocytogenes in a Patient with Allergy to Penicillin and Trimethoprim-Sulfamethoxazole

Design

Case report

Case presentation

A 63-year-old man with a known diagnosis of multiple myeloma was admitted due to fever and altered mental status. On physical examination, the most notable finding was neck stiffness, though no focal neurological deficits were observed. Cerebrospinal fluid (CSF) analysis revealed a leukocyte count of 158 cells/mm³ with a predominance of neutrophils (71%), a glucose level of 46 mg/dL, and a markedly elevated protein level of 151 mg/dL. Cultures of both blood and CSF grew Listeria monocytogenes (L. monocytogenes), which was susceptible to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ). Intravenous ampicillin therapy was promptly initiated.

On the 13th day of hospitalization, the patient developed motor aphasia. A computed tomography (CT) scan of the brain suggested an abscess in the left basal ganglia, which was confirmed by biopsy. TMP-SMZ was added to his treatment regimen, but within 24 hours, he developed a rash attributed to the drug. The TMP-SMZ was discontinued, and he continued on ampicillin monotherapy. After 37 days of inpatient care, the patient was discharged to continue intravenous ampicillin at home. However, 39 days later, he developed another rash consistent with a drug allergy, prompting discontinuation of ampicillin.

A follow-up CT scan at that time revealed a persistent but reduced brain abscess. The treatment strategy was switched to an oral regimen of linezolid (600 mg twice daily) and rifampin (300 mg twice daily), which was continued for an additional 107 days. This revised therapy was well tolerated, and the patient ultimately achieved full clinical recovery with complete radiographic resolution of the abscess.

Study Author Conclusions

Our success with the combination of linezolid and rifampin may offer a valid alternative therapy for brain abscess caused by L. monocytogenes.
References:

Leiti O, Gross JW, Tuazon CU. Treatment of brain abscess caused by Listeria monocytogenes in a patient with allergy to penicillin and trimethoprim-sulfamethoxazole. Clin Infect Dis. 2005;40(6):907-908. doi:10.1086/428355

 

Linezolid and dexamethasone experience in a serious case of Listeria rhombencephalitis

Design

Case report

Case presentation

A 63-year-old immunocompromised female with Takayasu’s arteritis developed Listeria monocytogenes rhombencephalitis. The patient, chronically treated with methotrexate and corticosteroids, presented with fever, headache, nausea, and vomiting. Although initial neuroimaging via cranial CT yielded no abnormalities, cerebrospinal fluid (CSF) analysis revealed pleocytosis with lymphocytic predominance, elevated protein levels (337 mg/dL), and decreased glucose concentrations (37 mg/dL). L. monocytogenes was isolated from the CSF culture, confirming the diagnosis. Empirical antiviral and broad-spectrum antibacterial therapies, acyclovir and ceftriaxone, were promptly discontinued, and first-line treatment with penicillin G plus gentamicin was initiated.

On the second day of antimicrobial therapy, intravenous linezolid (600 mg twice daily) was added due to deteriorating consciousness. Methylprednisolone was continued at a reduced dose due to immunosuppressive concerns, and intravenous dexamethasone was introduced during ICU admission when MRI revealed progressive pontine and periaqueductal signal changes, correlating with evolving brainstem dysfunction. The patient developed complications including respiratory failure, necessitating mechanical ventilation, Acinetobacter baumannii ventilator-associated pneumonia, and methicillin-resistant Staphylococcus haemolyticus bacteremia. Linezolid was discontinued on day 19 of antimicrobial therapy due to hematuria and thrombocytopenia. Gentamicin was also discontinued upon evidence of nephrotoxicity. Meropenem and colistin were added to address the nosocomial infections, but subsequently stopped as targeted therapy durations concluded. Despite the lengthy hospitalization (71 days total), serial CSF analyses showed gradual improvement in cellular and protein profiles, and the patient was successfully extubated. MRI at discharge revealed persistent but non-progressive pontine lesions. Seizures developed late in the clinical course and were managed with levetiracetam.

Study Author Conclusions

In the treatment of Listeria rhombencephalitis, the first-line antibiotic therapy is essential, although dexamethasone and linezolid can be added to firstline therapy for severe clinical forms.

 

References:

Yılmaz PÖ, Mutlu NM, Sertçelik A, Baştuğ A, Doğu C, Kışlak S. Linezolid and dexamethasone experience in a serious case of listeria rhombencephalitis. J Infect Public Health. 2016;9(5):670-674. doi:10.1016/j.jiph.2015.12.018