Solitary supratentorial Listeria monocytogenes brain abscess in an immunocompromised patient James A. West, MD, Anthony R. Onofrio, MD, Lauren C. Martinez, MD, Michael J. Opatowsky, MD, MBA, Cedric W. Spak, MD, MPH, and Kennith F. Layton, MD, MS
We describe an 81-year-old man receiving azacitidine monotherapy for myelodysplastic syndrome who was improving from Listeria monocytogenes bacteremia after receiving antibiotic therapy during an earlier hospital admission. Shortly after discharge he developed new-onset seizure activity, with brain imaging on subsequent admissions demonstrating a posterior right frontal lobe mass. Specimen cultures after resection of the mass revealed this to be a cerebral abscess related to L. monocytogenes. Brain abscesses related to this organism are rare.
L
isteria monocytogenes is a ubiquitous, opportunistic pathogen that rarely causes illness in healthy individuals. The immunocompromised and those with underlying illness are at greater risk for serious and potentially fatal infection. Approximately 20% of all listeriosis patients succumb to infection despite early aggressive treatment, with particularly elevated case fatality rates in those with comorbid illnesses and in immunocompromised states (1–4). While L. monocytogenes is a well-known cause of meningitis and encephalitis, brain abscesses related to this organism are rare and reported to occur in only 10% of all Listeria central nervous system (CNS) infections (4). Here we present the case of an immunocompromised man who developed L. monocytogenes bacteremia and a subsequent single supratentorial brain abscess. CASE DESCRIPTION An 81-year-old man with myelodysplastic syndrome was being treated with azacitidine monotherapy. He also had a remote history of acute myelogenous leukemia in remission, medically controlled atrial fibrillation, basal cell skin carcinoma resection, and treated prostate cancer. For 1 week, the patient complained only of intermittent fevers, reaching a maximum temperature of 102.4°F, and mild fatigue. Four days after the onset of fevers, blood cultures were drawn and he was started on levofloxacin and later on amoxicillin clavulanate once Gram-positive rods were isolated. Blood cultures grew L. monocytogenes, and the patient was hospitalized. He received intravenous piperacillin-tazobactam for 2 days. When sensitivity tests revealed susceptibility to ampicillin, penicillin G, and trimethoprim sulfamethoxazole, the treatment was changed to intravenous ampicillin, which continued for Proc (Bayl Univ Med Cent) 2015;28(3):337–339
his remaining 2 days in the hospital. Repeat blood cultures were negative at the time of discharge and he was afebrile. The patient was discharged home on continuous intravenous penicillin infusion. During the hospital admission there were no specific neurologic complaints, headaches, or altered sensorium. The morning after discharge, the patient had generalized jerking movements and left facial droop that lasted approximately 10 minutes while he remained lucid. Two additional seizure-like episodes occurred during transport to the emergency department. Noncontrast head computed tomography (CT) demonstrated a mass in the right frontoparietal region. Treatment with lorazepam and dexamethasone was initiated. Subsequent contrast-enhanced magnetic resonance imaging (MRI) of the brain showed a 2.2 cm rim-enhancing mass within the posterior right frontal lobe with mild surrounding edema (Figure 1). Intravenous ampicillin was restarted and levetiracetam treatment initiated. A 2-day posttreatment contrast-enhanced brain MRI demonstrated a slightly decreased volume of the mass, a similar degree of edema, and imaging characteristics most suggestive of an isolated cerebral abscess. A right frontal craniotomy was performed and a purulent cavity in the posterior right frontal lobe was resected. Specimens revealed acute inflammation consistent with cerebritis/abscess, although no organisms were identified by microscopy. Cultures of the abscess fluid were positive for L. monocytogenes susceptible to ampicillin, penicillin G, and trimethoprim sulfamethoxazole. No additional seizures occurred, and the patient was discharged on long-term intravenous ampicillin therapy, with surveillance imaging 7 days after the abscess was resected. DISCUSSION L. monocytogenes is a ubiquitous, Gram-positive, facultative intracellular bacterium that is typically acquired via food contamination (4). The groups considered at risk for listeriosis are pregnant women and neonates, the elderly, and immunocompromised or From the Department of Diagnostic Radiology (West, Onofrio, Opatowsky, Layton), the Department of Internal Medicine (Martinez), and the Division of Infectious Diseases (Spak), Baylor University Medical Center at Dallas. Corresponding author: James A. West, MD, Department of Diagnostic Radiology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail: [email protected]). 337
a
b
c
Figure 1. Baseline contrast-enhanced brain MRI. (a) T1 post-gadolinium image shows a 2.2 cm rim-enhancing mass within the posterior right frontal lobe (arrow) with surrounding edema. (b) Fluid-attenuated inversion recovery (FLAIR) image shows the rim of the mass to be hypointense (arrow) with a central core of heterogeneous signal. Increased signal within the subcortical white matter surrounding the mass reflects reactive vasogenic edema (arrowhead) that contributes to mild local mass effect with partial sulcul effacement. (c) Diffusion-weighted imaging reveals restricted diffusion predominantly within the rim of the mass (arrow), with less pronounced heterogeneous central diffusion restriction. (The confirmatory apparent diffusion coefficient [ADC] map is not shown.)
debilitated adults with underlying diseases (5). In nonpregnant adults, most cases have been associated with solid and hematologic malignancies, antineoplastic chemotherapy, immunosuppressant therapy, chronic liver disease, kidney disease, diabetes, collagen diseases, and HIV infection (5). In the immunocompetent, gastrointestinal exposure to a high inoculum of L. monocytogenes can result in a self-limited, febrile diarrheal gastroenteritis with a median duration of 27 to 42 hours (6). In the immunocompromised, gastrointestinal invasion can lead to bacteremia and seeding to various organs, with a particular predilection and invasive efficiency for the CNS, where it can cause meningitis, meningoencephalitis, rhombencephalitis, or, much less commonly, brain abscesses (5). Brain abscesses constitute approximately 10% of all L. monocytogenes CNS infections (4). Bacteremia is almost always present, and concomitant meningitis with isolation of L. monocytogenes from the cerebrospinal fluid occurs in 25% to 40% of brain abscess cases (4). Little information was available regarding the relative incidence of L. monocytogenes as the causative bacterium of cerebral abscesses in general. In an 8-year prospective multiinstitutional study by Prasad et al, L. monocytogenes was isolated from 0.8% of brain abscesses; however, this study did not include an organ transplant population, which could potentially constitute a significant number of patients who acquire Listeria brain abscesses (7). A retrospective study by Tattevin et al showed that L. monocytogenes accounted for 9% of brain abscesses in patients admitted to the intensive care unit, although patients with HIV were excluded from this study (8). While L. monocytogenes is not the most common cause of CNS infections, an epidemiologic study of bacterial meningitis in the US in 1995 found that it is nearly 10-fold more efficient than other neuroinvasive Gram-positive bacteria at invading 338
the CNS (9, 10). L. monocytogenes gains access to the CNS by transporting across the blood-brain or blood-choroid barriers within circulating leukocytes by a phagocyte-facilitated (Trojan horse) mechanism, direct invasion of blood-brain or blood-choroid endothelial cells by extracellular blood-borne bacteria, or retrograde migration into the brain within the axons of cranial nerves (9). Approximately 20% of all listeriosis patients succumb to infection despite early aggressive treatment, with particularly elevated case fatality rates in those who are immunocompromised or have an underlying illness or malignancy (1–4). Skogberg et al demonstrated a 32% mortality in those with underlying disease or in those receiving immunosuppressant medication, while no deaths were observed in healthy patients (3). Goulet et al demonstrated up to 40% mortality among those with L. monocytogenes bacteremia complicating a malignancy, with the highest incidence of infection occurring in patients with chronic lymphocytic leukemia and liver cancer and the highest case fatality rate in those with lung and pancreatic cancers (1). This high mortality rate is at least in part due to L. monocytogenes being a facultative intracellular pathogen with the capability to infect adjacent cells by direct extension through filopodia formation within the host cell, allowing the bacterium to circumvent extended exposure to the humoral immune response (9). This leaves the critical role of pathogen elimination to T lymphocyte–mediated cytotoxicity, which is typically impaired in various physiologically and pathologically immunocompromised states (9). There are currently no large controlled trials comparing treatments for listeriosis. Generally, ampicillin is considered the treatment of choice (4). Gentamicin is often added to ampicillin due to synergy that has been observed in vitro and in animal models; however, its use in clinical practice is often debated (11). In those with a penicillin allergy, trimethoprim sulfamethoxazole
Baylor University Medical Center Proceedings
Volume 28, Number 3
is considered an acceptable second-line treatment (12). Listeria is often in part or fully resistant to cephalosporins, so they are not typically recommended (13). Patients with a Listeria brain abscess should receive treatment for at least 6 weeks and be followed by serial neurological imaging, with MRI as the preferred modality (4).
6.
7.
8. 1.
2.
3.
4.
5.
Goulet V, Hebert M, Hedberg C, Laurent E, Vaillant V, De Valk H, Desenclos JC. Incidence of listeriosis and related mortality among groups at risk of acquiring listeriosis. Clin Infect Dis 2012;54(5):652–660. Mylonakis E, Hohmann EL, Calderwood SB. Central nervous system infection with Listeria monocytogenes. 33 years’ experience at a general hospital and review of 776 episodes from the literature. Medicine (Baltimore) 1998;77(5):313–336. Skogberg K, Syrjänen J, Jahkola M, Renkonen OV, Paavonen J, Ahonen J, Kontiainen S, Ruutu P, Valtonen V. Clinical presentation and outcome of listeriosis in patients with and without immunosuppressive therapy. Clin Infect Dis 1992;14(4):815–821. Lorber B. Listeria monocytogenes. In Bennett J, Dolin R, Blaser M, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 8th ed. Philadelphia, PA: Elsevier/Saunders, 2015:2383–2390. Vázquez-Boland JA, Kuhn M, Berche P, Chakraborty T, DomínguezBernal G, Goebel W, González-Zorn B, Wehland J, Kreft J. Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev 2001;14(3):584–640.
July 2015
9.
10.
11.
12.
13.
Dalton CB, Austin CC, Sobel J, Hayes PS, Bibb WF, Graves LM, Swaminathan B, Proctor ME, Griffin PM. An outbreak of gastroenteritis and fever due to Listeria monocytogenes in milk. N Engl J Med 1997;336(2):100–105. Prasad KN, Mishra AM, Gupta D, Husain N, Husain M, Gupta RK. Analysis of microbial etiology and mortality in patients with brain abscess. J Infect 2006;53(4):221–227. Tattevin P, Bruneel F, Clair B, Lellouche F, de Broucker T, Chevret S, Bédos JP, Wolff M, Régnier B. Bacterial brain abscesses: a retrospective study of 94 patients admitted to an intensive care unit (1980 to 1999). Am J Med 2003;115(2):143–146. Drevets DA, Bronze MS. Listeria monocytogenes: epidemiology, human disease, and mechanisms of brain invasion. FEMS Immunol Med Microbiol 2008;53(2):151–165. Schuchat A, Robinson K, Wenger JD, Harrison LH, Farley M, Reingold AL, Lefkowitz L, Perkins BA; Active Surveillance Team. Bacterial meningitis in the United States in 1995. N Engl J Med 1997; 337(14):970–976. Edmiston CE Jr, Gordon RC. Evaluation of gentamicin and penicillin as a synergistic combination in experimental murine listeriosis. Antimicrob Agents Chemother 1979;16(6):862–863. Michelet C, Avril JL, Cartier F, Berche P. Inhibition of intracellular growth of Listeria monocytogenes by antibiotics. Antimicrob Agents Chemother 1994;38(3):438–446. Hof H, Nichterlein T, Kretschmar M. Management of listeriosis. Clin Microbiol Rev 1997;10(2):345–357.
Solitary supratentorial Listeria monocytogenes brain abscess in an immunocompromised patient
339
We describe an 81-year-old man receiving azacitidine monotherapy for myelodysplastic syndrome who was improving from Listeria monocytogenes bacteremia after receiving antibiotic therapy during an earlier hospital admission. Shortly after discharge he developed new-onset seizure activity, with brain imaging on subsequent admissions demonstrating a posterior right frontal lobe mass. Specimen cultures after resection of the mass revealed this to be a cerebral abscess related to L. monocytogenes. Brain abscesses related to this organism are rare.
L
isteria monocytogenes is a ubiquitous, opportunistic pathogen that rarely causes illness in healthy individuals. The immunocompromised and those with underlying illness are at greater risk for serious and potentially fatal infection. Approximately 20% of all listeriosis patients succumb to infection despite early aggressive treatment, with particularly elevated case fatality rates in those with comorbid illnesses and in immunocompromised states (1–4). While L. monocytogenes is a well-known cause of meningitis and encephalitis, brain abscesses related to this organism are rare and reported to occur in only 10% of all Listeria central nervous system (CNS) infections (4). Here we present the case of an immunocompromised man who developed L. monocytogenes bacteremia and a subsequent single supratentorial brain abscess. CASE DESCRIPTION An 81-year-old man with myelodysplastic syndrome was being treated with azacitidine monotherapy. He also had a remote history of acute myelogenous leukemia in remission, medically controlled atrial fibrillation, basal cell skin carcinoma resection, and treated prostate cancer. For 1 week, the patient complained only of intermittent fevers, reaching a maximum temperature of 102.4°F, and mild fatigue. Four days after the onset of fevers, blood cultures were drawn and he was started on levofloxacin and later on amoxicillin clavulanate once Gram-positive rods were isolated. Blood cultures grew L. monocytogenes, and the patient was hospitalized. He received intravenous piperacillin-tazobactam for 2 days. When sensitivity tests revealed susceptibility to ampicillin, penicillin G, and trimethoprim sulfamethoxazole, the treatment was changed to intravenous ampicillin, which continued for Proc (Bayl Univ Med Cent) 2015;28(3):337–339
his remaining 2 days in the hospital. Repeat blood cultures were negative at the time of discharge and he was afebrile. The patient was discharged home on continuous intravenous penicillin infusion. During the hospital admission there were no specific neurologic complaints, headaches, or altered sensorium. The morning after discharge, the patient had generalized jerking movements and left facial droop that lasted approximately 10 minutes while he remained lucid. Two additional seizure-like episodes occurred during transport to the emergency department. Noncontrast head computed tomography (CT) demonstrated a mass in the right frontoparietal region. Treatment with lorazepam and dexamethasone was initiated. Subsequent contrast-enhanced magnetic resonance imaging (MRI) of the brain showed a 2.2 cm rim-enhancing mass within the posterior right frontal lobe with mild surrounding edema (Figure 1). Intravenous ampicillin was restarted and levetiracetam treatment initiated. A 2-day posttreatment contrast-enhanced brain MRI demonstrated a slightly decreased volume of the mass, a similar degree of edema, and imaging characteristics most suggestive of an isolated cerebral abscess. A right frontal craniotomy was performed and a purulent cavity in the posterior right frontal lobe was resected. Specimens revealed acute inflammation consistent with cerebritis/abscess, although no organisms were identified by microscopy. Cultures of the abscess fluid were positive for L. monocytogenes susceptible to ampicillin, penicillin G, and trimethoprim sulfamethoxazole. No additional seizures occurred, and the patient was discharged on long-term intravenous ampicillin therapy, with surveillance imaging 7 days after the abscess was resected. DISCUSSION L. monocytogenes is a ubiquitous, Gram-positive, facultative intracellular bacterium that is typically acquired via food contamination (4). The groups considered at risk for listeriosis are pregnant women and neonates, the elderly, and immunocompromised or From the Department of Diagnostic Radiology (West, Onofrio, Opatowsky, Layton), the Department of Internal Medicine (Martinez), and the Division of Infectious Diseases (Spak), Baylor University Medical Center at Dallas. Corresponding author: James A. West, MD, Department of Diagnostic Radiology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail: [email protected]). 337
a
b
c
Figure 1. Baseline contrast-enhanced brain MRI. (a) T1 post-gadolinium image shows a 2.2 cm rim-enhancing mass within the posterior right frontal lobe (arrow) with surrounding edema. (b) Fluid-attenuated inversion recovery (FLAIR) image shows the rim of the mass to be hypointense (arrow) with a central core of heterogeneous signal. Increased signal within the subcortical white matter surrounding the mass reflects reactive vasogenic edema (arrowhead) that contributes to mild local mass effect with partial sulcul effacement. (c) Diffusion-weighted imaging reveals restricted diffusion predominantly within the rim of the mass (arrow), with less pronounced heterogeneous central diffusion restriction. (The confirmatory apparent diffusion coefficient [ADC] map is not shown.)
debilitated adults with underlying diseases (5). In nonpregnant adults, most cases have been associated with solid and hematologic malignancies, antineoplastic chemotherapy, immunosuppressant therapy, chronic liver disease, kidney disease, diabetes, collagen diseases, and HIV infection (5). In the immunocompetent, gastrointestinal exposure to a high inoculum of L. monocytogenes can result in a self-limited, febrile diarrheal gastroenteritis with a median duration of 27 to 42 hours (6). In the immunocompromised, gastrointestinal invasion can lead to bacteremia and seeding to various organs, with a particular predilection and invasive efficiency for the CNS, where it can cause meningitis, meningoencephalitis, rhombencephalitis, or, much less commonly, brain abscesses (5). Brain abscesses constitute approximately 10% of all L. monocytogenes CNS infections (4). Bacteremia is almost always present, and concomitant meningitis with isolation of L. monocytogenes from the cerebrospinal fluid occurs in 25% to 40% of brain abscess cases (4). Little information was available regarding the relative incidence of L. monocytogenes as the causative bacterium of cerebral abscesses in general. In an 8-year prospective multiinstitutional study by Prasad et al, L. monocytogenes was isolated from 0.8% of brain abscesses; however, this study did not include an organ transplant population, which could potentially constitute a significant number of patients who acquire Listeria brain abscesses (7). A retrospective study by Tattevin et al showed that L. monocytogenes accounted for 9% of brain abscesses in patients admitted to the intensive care unit, although patients with HIV were excluded from this study (8). While L. monocytogenes is not the most common cause of CNS infections, an epidemiologic study of bacterial meningitis in the US in 1995 found that it is nearly 10-fold more efficient than other neuroinvasive Gram-positive bacteria at invading 338
the CNS (9, 10). L. monocytogenes gains access to the CNS by transporting across the blood-brain or blood-choroid barriers within circulating leukocytes by a phagocyte-facilitated (Trojan horse) mechanism, direct invasion of blood-brain or blood-choroid endothelial cells by extracellular blood-borne bacteria, or retrograde migration into the brain within the axons of cranial nerves (9). Approximately 20% of all listeriosis patients succumb to infection despite early aggressive treatment, with particularly elevated case fatality rates in those who are immunocompromised or have an underlying illness or malignancy (1–4). Skogberg et al demonstrated a 32% mortality in those with underlying disease or in those receiving immunosuppressant medication, while no deaths were observed in healthy patients (3). Goulet et al demonstrated up to 40% mortality among those with L. monocytogenes bacteremia complicating a malignancy, with the highest incidence of infection occurring in patients with chronic lymphocytic leukemia and liver cancer and the highest case fatality rate in those with lung and pancreatic cancers (1). This high mortality rate is at least in part due to L. monocytogenes being a facultative intracellular pathogen with the capability to infect adjacent cells by direct extension through filopodia formation within the host cell, allowing the bacterium to circumvent extended exposure to the humoral immune response (9). This leaves the critical role of pathogen elimination to T lymphocyte–mediated cytotoxicity, which is typically impaired in various physiologically and pathologically immunocompromised states (9). There are currently no large controlled trials comparing treatments for listeriosis. Generally, ampicillin is considered the treatment of choice (4). Gentamicin is often added to ampicillin due to synergy that has been observed in vitro and in animal models; however, its use in clinical practice is often debated (11). In those with a penicillin allergy, trimethoprim sulfamethoxazole
Baylor University Medical Center Proceedings
Volume 28, Number 3
is considered an acceptable second-line treatment (12). Listeria is often in part or fully resistant to cephalosporins, so they are not typically recommended (13). Patients with a Listeria brain abscess should receive treatment for at least 6 weeks and be followed by serial neurological imaging, with MRI as the preferred modality (4).
6.
7.
8. 1.
2.
3.
4.
5.
Goulet V, Hebert M, Hedberg C, Laurent E, Vaillant V, De Valk H, Desenclos JC. Incidence of listeriosis and related mortality among groups at risk of acquiring listeriosis. Clin Infect Dis 2012;54(5):652–660. Mylonakis E, Hohmann EL, Calderwood SB. Central nervous system infection with Listeria monocytogenes. 33 years’ experience at a general hospital and review of 776 episodes from the literature. Medicine (Baltimore) 1998;77(5):313–336. Skogberg K, Syrjänen J, Jahkola M, Renkonen OV, Paavonen J, Ahonen J, Kontiainen S, Ruutu P, Valtonen V. Clinical presentation and outcome of listeriosis in patients with and without immunosuppressive therapy. Clin Infect Dis 1992;14(4):815–821. Lorber B. Listeria monocytogenes. In Bennett J, Dolin R, Blaser M, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 8th ed. Philadelphia, PA: Elsevier/Saunders, 2015:2383–2390. Vázquez-Boland JA, Kuhn M, Berche P, Chakraborty T, DomínguezBernal G, Goebel W, González-Zorn B, Wehland J, Kreft J. Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev 2001;14(3):584–640.
July 2015
9.
10.
11.
12.
13.
Dalton CB, Austin CC, Sobel J, Hayes PS, Bibb WF, Graves LM, Swaminathan B, Proctor ME, Griffin PM. An outbreak of gastroenteritis and fever due to Listeria monocytogenes in milk. N Engl J Med 1997;336(2):100–105. Prasad KN, Mishra AM, Gupta D, Husain N, Husain M, Gupta RK. Analysis of microbial etiology and mortality in patients with brain abscess. J Infect 2006;53(4):221–227. Tattevin P, Bruneel F, Clair B, Lellouche F, de Broucker T, Chevret S, Bédos JP, Wolff M, Régnier B. Bacterial brain abscesses: a retrospective study of 94 patients admitted to an intensive care unit (1980 to 1999). Am J Med 2003;115(2):143–146. Drevets DA, Bronze MS. Listeria monocytogenes: epidemiology, human disease, and mechanisms of brain invasion. FEMS Immunol Med Microbiol 2008;53(2):151–165. Schuchat A, Robinson K, Wenger JD, Harrison LH, Farley M, Reingold AL, Lefkowitz L, Perkins BA; Active Surveillance Team. Bacterial meningitis in the United States in 1995. N Engl J Med 1997; 337(14):970–976. Edmiston CE Jr, Gordon RC. Evaluation of gentamicin and penicillin as a synergistic combination in experimental murine listeriosis. Antimicrob Agents Chemother 1979;16(6):862–863. Michelet C, Avril JL, Cartier F, Berche P. Inhibition of intracellular growth of Listeria monocytogenes by antibiotics. Antimicrob Agents Chemother 1994;38(3):438–446. Hof H, Nichterlein T, Kretschmar M. Management of listeriosis. Clin Microbiol Rev 1997;10(2):345–357.
Solitary supratentorial Listeria monocytogenes brain abscess in an immunocompromised patient
339
