Abstract & Commentary
By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
Source: Brouwer MC, et al. Community-acquired Listeria monocytogenes meningitis in adults. Clin Infect Dis. 2006; 43:1233-1238.
Of 696 episodes of community-acquired meningitis in adults identified by the nationwide Dutch Meningitis Cohort study from 1998 to 2002, 30 (4%) were due to Listeria monocytogenes. The mean age was 65 ± 18 years; all 10 of the previously immunocompetent patients were >50 years of age.
Symptoms were present for > 4 days prior to presentation in 8 (27%) patients. While the entire meningitis triad of nuchal rigidity, fever and altered mental status was present in only 43% of patients, 97% had at least 2 of 4 symptoms and/or signs if headache is added to the triad. Ten percent were comatose (Glasgow coma score ≤ 8), and an additional 70% had altered mental status (Glasgow score < 14). Eighteen of 23 had a normal brain CT on admission, but left unstated is whether IV contrast was administered. Abnormalities noted on CT included cerebral edema in 2 patients and a recent cerebral infarction in one. A single MRI was performed, and it was normal.
All patients underwent lumbar puncture. The CSF pressure was > 250 mm of water in 5 of 8 for whom manometry was performed. CSF WBC ranged from 24 to 16,003 WBC/ml, with a median value of 620 WBC/ml; 13% had < 100 WBC/ml. There was no relationship between CSF leukocyte count and the presence or absence of immunocompromise. The median CSF protein concentration was 2.52 g/L (range 1.1-19.3 g/L) and the median CSF: blood ratio of glucose was 0.30 (range 0.03-0.86), but 23% of patients "had no individual CSF findings indicative of bacterial meningitis."
A Gram stain was performed on the CSF of 25 patients and was negative in 60%, demonstrated Gram-positive bacilli in 28%, and Gram-negative bacilli in 2 patients (4%). CSF culture yielded L. monocytogenes in all patients (this was a criterion for inclusion the cohort) and 12 (46%) of 26 had positive blood cultures. Three-fourths of patients were hyponatremic.
Initial antibiotic therapy was inadequate (not active against L. monocytogenes) in 30%, but this did not appear to affect mortality, which occurred in 5 (17%) patients. All 5 deaths occurred in the first 3 days of hospitalization.
Adults at increased risk of Listeria infection include pregnant women (especially during the 3rd trimester), those with lymphoma and other malignancies, and those receiving immunosuppressive therapy for organ transplantation and other indications. Cases have been reported in recipients of anti-TNF therapy with both infliximab and etanercept. In addition, however, approximately one-third with infection have none of these underlying problems, but almost all are greater than 50 years of age.
While, as in this study, there is a broad range of acuity and severity with which meningitis due to L. monocytogenes presents in adults, in many cases the presentation is subacute. Thus, Brouwer and colleagues report that just over one-fourth of patients were ill for 4 or more days prior to presentation. In some cases, the illness may be more accurately termed meningoencephalitis, rather than meningitis, because of clinical evidence of parenchymal involvement of the brain. Patients may present with seizures, cranial neuropathies, hemiplegia, and other evidence of focal disease, as well as with global cerebral dysfunction manifested as coma. L. monocytogenes, in fact, has an unusual propensity to invade brain parenchyma, causing cerebritis, which may progress to frank abscess formation. The presence of a brain stem abscess should especially alert the clinician to the Listeria as the possible etiology of the infection.
A subacute presentation together with, in some cases, CSF lymphocytosis, makes it necessary to differentiate meningitis due to L. monocytogenes from that due to Mycobacterium tuberculosis and other causes of granulomatous meningitis. Since only a minority of patients with Listeria meningitis have a positive CSF Gram stain, the diagnosis generally remains in doubt until CSF and/or blood cultures yield the organism. Even in cases in which organisms are microscopically visualized, their appearance may be misleading, such as in this study in which the occasional Gram-variability of the organism led to the identification of Gram negative, rather than Gram positive bacilli in 2 cases. Furthermore, even when the organism stains Gram positive, it may be mistaken for diphtheroids and inappropriately discounted. Listeria can be distinguished from diphtheroids in the microbiology laboratory by their beta-hemolysis and tumbling motility.