Chapter 132. Infections Caused by Listeria monocytogenes (Part 3)

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Meningitis L. monocytogenes causes ~5–10% of all cases of community-acquired bacterial meningitis in adults in the United States. Case-fatality rates are reported to be 15–26% and do not appear to have changed over time. This diagnosis should be considered in all older or chronically ill adults with "aseptic" meningitis. The presentation is more frequently subacute (with illness developing over several days) than in meningitis of other bacterial etiologies, and nuchal rigidity and meningeal signs are less common. Photophobia is infrequent. Focal findings and seizures are common in some but not all series. ...

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Chapter 132. Infections Caused by Listeria monocytogenes (Part 3) Meningitis L. monocytogenes causes ~5–10% of all cases of community-acquired bacterial meningitis in adults in the United States. Case-fatality rates are reported to be 15–26% and do not appear to have changed over time. This diagnosis should be considered in all older or chronically ill adults with "aseptic" meningitis. The presentation is more frequently subacute (with illness developing over several days) than in meningitis of other bacterial etiologies, and nuchal rigidity and meningeal signs are less common. Photophobia is infrequent. Focal findings and seizures are common in some but not all series. The CSF profile in listerial meningitis most often shows white blood cell (WBC) counts in the range of 100– 5000/µL (rarely higher); 75% of patients have WBC counts below 1000/µL, usually with a neutrophil predominance more modest than that in other bacterial
meningitides. Low glucose levels and positive results on Gram's staining are found ~30–40% of the time. Meningoencephalitis and Focal CNS Infection L. monocytogenes can directly invade the brain parenchyma, producing either cerebritis or focal abscess. Approximately 10% of cases of CNS infection are macroscopic abscesses resulting from bacteremic seeding; the affected patients often have positive blood cultures. Concurrent meningitis can exist, but the CSF may appear normal. Abscesses can be misdiagnosed as metastatic or primary tumors and, in rare instances, occur in the cerebellum and the spinal cord. Invasion of the brainstem results in a characteristic severe rhombencephalitis, usually in otherwise healthy older adults. The presentation may be biphasic, with a prodrome of fever and headache followed by asymmetric cranial nerve deficits, cerebellar signs, and hemiparetic and hemisensory deficits. Respiratory failure can occur. The subacute course and the often minimally abnormal CSF findings may delay the diagnosis, which may be suggested by MRI images showing ring-enhancing lesions after gadolinium contrast and hyperintense lesions on diffusion-weighted imaging. MRI is superior to CT for the diagnosis of these infections. Other Focal Infections Focal infections of visceral organs; the eye; the pleural, peritoneal and pericardial spaces; and the bones and joints have all been reported.
Infection in Pregnancy and Neonatal Infection Listeriosis in pregnancy is a severe and important infection. The usual presentation is a nonspecific acute or subacute febrile illness with myalgias, arthralgias, backache, and headache. Pregnant women with listeriosis are usually bacteremic. This syndrome should prompt blood cultures, especially in the absence of another reasonable explanation. Involvement of the CNS is rare in the absence of other risk factors. Preterm delivery is a common complication, and the diagnosis may be made only postpartum. As many as 70–90% of fetuses from infected women can become infected. Prepartum treatment of bacteremic women enhances the chances of delivery of a healthy infant. Women usually do well after delivery: maternal deaths are very rare, even when the diagnosis is made late in pregnancy or postpartum. Overall mortality rates for fetuses infected in utero approach 50% in some series; among live-born neonates treated with antibiotics, mortality rates are much lower (~20%). Granulomatosis infantiseptica is an overwhelming listerial fetal infection with miliary microabscesses and granulomas, most often in the skin, liver, and spleen. Less severe neonatal infection acquired in utero presents at birth. "Late-onset" neonatal illness typically develops ~10 days after delivery but can occur up to a month postpartum. Mothers of infants with late-onset disease are not ill. Infections Caused by Listeria monocytogenes: Treatment
No clinical trials have compared antimicrobial agents for the treatment of L. monocytogenes infections. Data obtained in studies conducted in vitro and in animals as well as observational clinical data indicate that ampicillin is the drug of choice, although penicillin is also highly active. Adults should receive IV ampicillin at high doses (2 g every 4 h), and most experts recommend the addition of gentamicin for synergy (1.0–1.7 mg/kg every 8 h). TMP-SMX, given IV, is the best alternative for the penicillin-allergic patient (15–20 mg of TMP/kg per day in divided doses every 6–8 h). The dosages recommended cover CNS infection and bacteremia (see below for duration); dosages must be reduced for patients with renal insufficiency. One small nonrandomized study supports a combination of ampicillin and TMP-SMX. Case reports document success with vancomycin, tetracycline, and erythromycin, although there are also reports of clinical failure with all three agents. Imipenem and the newer quinolones are possible alternative agents that have been efficacious in animal models, but clinical experience is very limited. Cephalosporins are not effective and should not be used. Neonates should receive ampicillin and gentamicin at doses based on weight. The duration of therapy depends on the syndrome: 2 weeks for bacteremia, 3 weeks for meningitis, 6–8 weeks for brain abscess/encephalitis, and 4–6 weeks for endocarditis in both neonates and adults. Early-onset neonatal disease may be more severe and should be treated for >2 weeks. Complications and Prognosis
About 50–70% of individuals who are promptly diagnosed and treated recover fully, but permanent neurologic sequelae are common in patients with brain abscess or rhombencephalitis. Of 100 live-born treated neonates in one series, 60% recovered fully, 24% died, and 13% had long-term neurologic or other complications. Prevention Healthy persons should take standard precautions to prevent food-borne illness: fully cooking meats, washing fresh vegetables, carefully cleaning utensils, and avoiding unpasteurized dairy products. In addition, persons at risk for listeriosis, including pregnant women, should avoid soft cheeses (although hard cheeses and yogurt are not problematic) and should avoid or thoroughly reheat ready-to-eat and delicatessen foods, even though the absolute risk they pose is relatively low. Further Readings Bakardjiev AI et al: Listeria monocytogenes traffics from maternal organs to the placenta and back. PLoS Pathog 2:e66, 2006 Bortolussi R, Mailman TM: Listeriosis, in Infectious Disease of the Fetus and Newborn Infant, 6th ed, S Remington et al (eds). Philadelphia, Elsevier
Saunders, 2005, p 465 Hamon M et al: Listeria monocytogenes: A multifaceted model. Nat Rev Microbiol 4:423, 2006 [PMID: 16710323] Mylonakis E et al: Listeriosis during pregnancy: A case series and review of 222 cases. Medicine (Baltimore) 81:260, 2002 [PMID: 12169881] Ooi ST, Lorber B: Gastroenteritis due to Listeria monocytogenes. Clin Infect Dis 40:1327, 2005 [PMID: 15825036] Portnoy DA (section ed): The listeriae, in Gram-Positive Pathogens, 2d edition, VA Fischetti et al (eds). Washington, DC, ASM Press, 2006, Section 4 Tweten RK: Cholesterol-dependent cytolysins, a family of versatile pore- forming toxins. Infect Immun 73:6199, 2005 [PMID: 16177291]