Brain Abscess due to Listeria monocytogenes

Introduction Unlike more common causes of bacterial meningitis, Listeria monocytogenes can infect the brain parenchyma itself, in addition to the meninges. Meningitis is the most common central nervous system (CNS) infection caused by L. monocytogenes(26), and a brainstem encephalitis (rhombencephalitis) is also well recognized (2). Brain abscess accounts for approximately 10% of CNS infections by L. monocytogenes(26). Listerial brain abscess is usually reported as an infectious complication of immunosuppressed patients and is commonly associated with concomitant meningitis and bacteremia (12). Optimal therapy and neurologic outcomes have not been clearly defined for this form of listerial infection. Since listerial brain abscess was last reviewed (12), there have been 20 additional cases described in the literature, including the first listerial brain abscess seen in a patient with acquired immunodeficiency syndrome (AIDS) and the first seen in an infant. The previous review also excluded cases of cerebritis, which is known to be an early stage of brain abscess development (27). Prompted by 5 cases of listerial brain abscess seen at our institution, we reviewed the world’s literature and identified 34 cases of listerial brain abscess (11 of which were described as cerebritis). Of our 5 cases, 3 are the first reported cases of listerial brain abscess in cardiac transplant recipients. This review summarizes the demographic characteristics, clinical presentations, and outcomes after treatment of our 5 cases and of the 34 cases reported in the literature from 1966 to 2000. Materials and Methods We reviewed the medical and laboratory records of all patients (n = 75) with positive cultures for L. monocytogenes isolated in the Stanford University Hospital microbiology laboratory between January 1981 and January 2001. Of these 75 patients, 5 were found to have listerial brain abscess. L. monocytogenes was identified by standard laboratory methods from blood, cerebrospinal fluid (CSF), or brain tissue (4). Susceptibility tests were performed in the clinical microbiology laboratory by the disk susceptibility method as recommended by the National Committee for Clinical Laboratory Standards (30). Hospital records were reviewed for age, gender, associated medical conditions, presenting symptoms and signs, clinical laboratory results, radiologic studies, clinical diagnosis, treatment, and outcome. We reviewed the English-language literature from 1966 to December 2000 for previously reported cases of brain abscess due to L. monocytogenes using a computer-based search of MEDLINE (National Library of Medicine, Bethesda, MD). The key terms used in the search included Listeria monocytogenes, Listeria infections, central nervous system infections, and brain abscess. References of the identified articles were also examined for additional cases. Two criteria were required for inclusion of a case of listerial brain abscess: 1) isolation of L. monocytogenes from blood, CSF, or brain tissue, and 2) macroscopic brain abscess or cerebritis, at least 1 cm in diameter, identified at autopsy or surgery or revealed as a focal ring-enhancing lesion on brain imaging. Cases of rhombencephalitis (including multiple brainstem abscesses less than 1 cm each) and diffuse granulomatous encephalitis (including granulomatosis infantiseptica in neonates) were excluded. Cases that lacked sufficient demographic and clinical data for meaningful analysis (15,22,34), a case of a septic brain infarct (31), and a case with negative cultures for L. monocytogenes(49) were also excluded. Case Reports Case 1 (Patient 35, Tables 1A, 1B and 2)TABLE 1: Clinical characteristics of patients with listerial brain abscessTABLE 1: Continued Clinical characteristics of patients with listerial brain abscessTABLE 2: Treatment and outcome of patients with listerial brain abscessA 50-year-old Indian man was admitted to the cardiac transplant service on 10 November 1991. Past history included heart transplantation 5 months earlier, diabetes mellitus, and a polymicrobial perianal abscess 2 months earlier. One month earlier he had received methylprednisolone for grade 3 graft rejection. Headaches and emesis began 6 days before admission, followed by fever and progressive mental status changes. His immunosuppressive regimen included azathioprine, cyclosporine, and prednisone. On admission he was unresponsive. Examination revealed a temperature of 38.3 °C, left hemiparesis, and a perianal ulcer. A lumbar puncture was performed and the CSF revealed only mild pleocytosis. Cultures of CSF and blood were negative. A computed tomography (CT) brain scan revealed a focal lesion in the right frontal lobe. Penicillin-G (3 million units IV q4h), ceftriaxone, and metronidazole were started empirically. Stereotactic aspiration of the frontal lobe lesion yielded 2 cc of purulent material, and brain biopsy revealed necrotic tissue and an acute inflammatory infiltrate, consistent with cerebritis. The brain aspirate grew L. monocytogenes, susceptible to ampicillin, penicillin-G, and gentamicin. Biopsy of the perianal ulcer also grew L. monocytogenes with identical susceptibilities. The antimicrobial regimen was changed to ampicillin (3 g IV q6h) and gentamicin (90 mg IV q8h) on hospital day 3. Repeat CT brain scan 2 weeks later revealed 2 discrete ring-enhancing abscesses: 1 in the right frontal lobe (the previous detected area of cerebritis) and 1 in the right basal ganglia. Ampicillin and gentamicin were continued, followed by slow neurologic recovery. Six weeks after admission repeat CT brain scan showed interval decrease in the size of the 2 abscesses. Ampicillin was given for a total of 128 days, and gentamicin for 100 days. The patient had full neurologic recovery. The patient died 4 years later from a cardiac arrest sustained after a traumatic fall. Case 2 (Patient 36, Tables 1 and 2) A 51-year-old Fijian man was admitted to the cardiac transplant service on 8 November 1990 with a history of cardiac transplant 3 months before admission. Present illness consisted of 2 days of fever, 2.5 weeks of headaches, and increasing cytomegalovirus titers. His immunosuppressive regimen included azathioprine, cyclosporine, and prednisone. The patient’s temperature was 37.5 °C and his neurologic exam was nonfocal. A magnetic resonance imaging (MRI) scan of the brain was obtained, which revealed a right parietal ring-enhancing lesion. A stereotactic brain aspiration was performed. Brain abscess aspirate and blood cultures grew L. monocytogenes, susceptible to ampicillin and gentamicin. Ampicillin (2 g IV q6h) and gentamicin (90 mg IV q8h) were started. The patient improved rapidly and was discharged 2 weeks later on IV ampicillin alone for a total of 42 days. There were no complications or neurologic sequelae. He died 2 years later with congestive heart failure and graft failure. Case 3 (Patient 37, Tables 1 and 2) A 37-year-old Caucasian man was admitted to neurosurgery on 12 August 1981 after 2 weeks of severe retroorbital headaches, 5 days of behavioral changes, and 1 day of fever. He had a heart transplantation 4 months before admission, and was taking prednisone and cyclosporine. On physical examination, his temperature was 38.5 °C, and he was lethargic but oriented. Neurologic examination revealed left hemiparesis and right-sided papilledema. CT brain scan on the day of admission showed an enhancing right frontal lobe lesion. A right frontal burr hole was placed, and 5 cc of necrotic, purulent material was aspirated. Brain aspirate and blood cultures grew L. monocytogenes, susceptible to penicillin-G, gentamicin, and chloramphenicol. The patient was started on penicillin-G (2.25 million units IV q3h). Several days after admission, he had worsening headaches and hypertension. A repeat CT brain scan suggested progressive encapsulation and organization of the frontal lobe abscess. On hospital day 6, the patient had a right frontal craniotomy for excision of the abscess. The brain material again grew L. monocytogenes. One week later, a frontal epidural hematoma was detected on follow-up CT, and aspiration of the hematoma grew Serratia marcescens. Cefotaxime and gentamicin (70 mg IV q8h) were added to the antibiotic regimen, and continued for 40 and 14 days, respectively. The patient’s abscess was not apparent on head CT 1 month after diagnosis, and he was continued on IV penicillin-G therapy for a total of 55 days. Information about his long-term outcome or neurologic sequelae was not available. Case 4 (Patient 38, Tables 1 and 2) A 66-year-old Caucasian woman presented to the medical service on 6 October 1989 with nausea, vomiting, abdominal pain, and diarrhea. She had a 4-month history of acute myelogenous leukemia and a 30-year history of Crohn disease. She had been taking prednisone (60 mg PO qd) for a recent flare of her Crohn disease. On admission the patient was afebrile and had no neurologic signs. She received intravenous steroids, total parenteral nutrition, and bowel rest for a presumed exacerbation of Crohn disease. On hospital day 7, she developed right-sided facial and upper extremity weakness. A CT brain scan revealed a ring-enhancing mass in the left frontoparietal area. Ceftriaxone and metronidazole were started. Lumbar puncture revealed a mild lymphocytic pleocytosis, with negative Gram stain and culture. A stereotactic brain biopsy of the left frontal lobe lesion was performed on hospital day 8, and a Gram stain of the purulent material showed rare neutrophils and no organisms. However, both the brain biopsy and blood cultures drawn on the same day grew L. monocytogenes. Her antibiotic regimen was changed to ampicillin (2.5 g IV q6h) on hospital day 10. Intravenous ampicillin was continued for a total of 25 days. At a 6-month follow-up visit, the patient had no residual neurologic deficits. Case 5 (Patient 39, Tables 1 and 2) A 71-year-old Caucasian man was admitted to the cardiology service with 2–3 weeks of fatigue, anorexia, disorientation, and a recent fall. He had a past history of aortic, tricuspid, and mitral valve replacement due to rheumatic heart disease, and diabetes mellitus. On examination, he was afebrile, the neurologic exam was nonfocal, and a loud systolic ejection murmur was present at the left upper sternal border. CT brain scan revealed cortical atrophy, but no hemorrhage or masses. On hospital day 3, the patient’s temperature rose to 38.9 °C and he became more lethargic. The following day a lumbar puncture was performed, with CSF containing 112 white blood cells/mm 3 (82% neutrophils, 6% monocytes, 9% lymphocytes), 109 red blood cells/mm 3 , 89 mg/dL glucose, and 90 mg/dL protein. No organisms were seen on Gram stain. Cefotaxime and gentamicin were started. Blood cultures from hospital day 3 grew L. monocytogenes, sensitive to ampicillin. His antibiotic regimen was changed to ampicillin (2 g IV q4h). Repeat CT brain scan on hospital day 5 revealed a new low-attenuation lesion in the right cerebellum with mass effect on the adjacent fourth ventricle. The patient subsequently developed a right-sided flaccid hemiparesis and increasing somnolence. He died on hospital day 11. Autopsy revealed a 3.0 right abscess. Gram stain of the abscess showed of the valve was found on no organisms were seen on Gram stain of the data data and clinical characteristics of our 5 patients and 34 patients from the literature are in patients were (n = The was years were years or The (Patient is a case in that is the only case of a listerial brain from granulomatosis described in a patients had medical (n = 36, or were immunosuppressive therapy (n = at the of was for listerial infection was including immunodeficiency infection or or or therapy for including immunosuppressive in transplant recipients. patients in this were to have conditions, including leukemia or (n = infection (n = or or (n = of the patients in this was 3 patients and were previously or had no reported or apparent all 3 were years patients had a history of acute or patients and had acute Two of these patients were in 10 for months and 12 for 3 were both at the of the of brain and 10 had a history of and was in for 4 but was with CNS 1 month before of brain abscess and was and prednisone. Two patients and had a history of lymphocytic had lymphocytic leukemia for 4 and was prednisone and before the of brain abscess. had lymphocytic leukemia for 5 years that was in for 2 years before the of brain after 8 of and had acute myelogenous developed listerial bacteremia 3 days after her transplant for acute had been 4 months before the of the brain abscess and to that was with 6 had a leukemia that was not with no of stage of or of immunosuppressive patients had a history of transplant before the of listerial brain abscess. patients had for including disease, and Of the patients of of listerial brain abscess from 3 months to 6 years after patients 7, and had a history of graft or transplant and 2 of these patients had received of methylprednisolone 1 week before the of listerial brain abscess. patients were immunosuppressive therapy at the of brain abscess Six were prednisone and 1 for and 1 (Patient was immunosuppressive of the listerial brain abscess cases at our in of heart total had an heart transplant for 5 months before the of brain and had 2 of graft months and 1 month before with and respectively. had a cardiac transplant for 3 months before diagnosis, and had a cardiac transplant 4 months before the of brain abscess. had a history of graft before the of brain abscess. 3 patients were taking immunosuppressive therapy including and prednisone and and were taking of the cardiac transplant was taking at the of or before the of listerial brain abscess. and symptoms patients had a of with a fever and focal neurologic on physical of the 34 patients in of symptoms was reported had symptoms for 1 week or and had symptoms for 2 weeks or One patient (Patient had headaches, fatigue, and for 5 months before the of listerial brain abscess. However, he had a history of antibiotic and the of symptoms was not is not symptoms were to be to listerial infection by the for the patients had than 37.5 °C or were to be neurologic were reported for all patients (n = had mental status changes, including or behavioral changes, before the of listerial brain abscess. was not as in patients patients developed focal neurologic to the brain abscess of these patients (n = had left or right included isolated 34 and (Patient focal (Patient facial (Patient (Patient (Patient (Patient and and (Patient Laboratory The white blood was reported in of the 12 of these patients had white blood than or to 3 CSF was for in patients lumbar were performed before of brain abscess on brain CSF was for analysis after ring-enhancing were on brain imaging in patients 8, and CSF laboratory were given in 25 of the cases, all of which had The CSF were not reported for 6, and were reported as in and There was a of CSF pleocytosis, from 1 to white cells/mm 3 the cases for which the CSF white blood was neutrophils in 10 cases, in 3 cases, and in 3 cases. Of the patients with reported CSF had CSF 40 the 20 patients with reported CSF 5 had 40 blood were not for in most cases. Blood cultures were positive in of the patients with blood However, CSF cultures were less to be positive (11 of Of the 25 patients with CSF, (n = were on culture. Brain tissue or material was for in patients, and an additional brain tissue was at the of autopsy (Patient of these patients had positive brain for L. monocytogenes. The patient with negative brain aspirate cultures for L. monocytogenes (Patient had received ampicillin g and 10 mg for days before the of the abscess. No additional organisms were isolated from of the brain tissue of brain abscesses listerial brain abscesses were (n = of the 12 patients had 2 or more discrete 2 and had 1 abscess with multiple abscesses on imaging. patients developed listerial brain in the frontal parietal or both patients had abscesses in the including the and basal ganglia. The patients had abscesses in the cerebellum (n = 2) or area (n = Treatment and outcome received a of for the of listerial brain abscess was patients received for treatment patients a 12 of had or excision of the brain abscess as a of patients had brain for had a is the was performed for or but 1 patient (Patient had reported Of the patients with reported the 14 had residual neurologic on follow-up patients with no residual neurologic and 2 patients had no reported neurologic Of the in the patients died of causes to be from listerial brain abscess 3, 7, 35, 36, and The 6 6, and were due to or in to the listerial infection by the 1 of these patients had a for abscess aspiration or (Patient 2 6 patients were treatment at the of these patients, between and 1 month after were used in the which included ampicillin, penicillin-G, and in Of the in the present the of antimicrobial therapy from 2 weeks to 14 There was no in the of treatment with and neurologic sequelae. Six in this were to listerial brain abscess. Two patients were a regimen 1 and 3 were an regimen and and 1 was at the of (Patient 6 patients were with for less than 1 The of ampicillin and an was the most common antimicrobial regimen used in the present of these patients were with between 4 weeks and 4 months of ampicillin, 2 days to 3 months of gentamicin or 3 patients with reported outcomes received in with or ampicillin were The of in these patients from 14 days to The outcome of the patient (Patient with alone was not in patients with listerial brain abscess with of the were with were with both and of the brain abscess 1 patient (Patient of the 6 to the listerial infection had in addition to intravenous antibiotic This patient had aspiration of the abscess more than 14 days after to listerial brain abscess in patients with alone to the more causes of bacterial meningitis, L. monocytogenes for the brain parenchyma itself, as well as for the meninges. addition to bacterial meningitis, L. monocytogenes granulomatous and macroscopic brain abscess Meningitis is the most common CNS of L. monocytogenes infection L. monocytogenes accounts for of cases of bacterial meningitis in the with an of approximately is only to as a for bacterial meningitis in years of age, and is the most common of bacterial meningitis in patients with transplant or therapy A form of listerial CNS infection is an acute brainstem infection by hemiparesis, of and failure (2). listerial brain abscesses are and for approximately 10% of listerial CNS infection the present of patients with listerial brain most patients were and the was patients in this case had a known or illness for listerial infection. is a for development of infection by L. monocytogenes(26), and at patients with or patients with infection or and patients with or immunosuppressive patients in this had that required or of 10 had leukemia or 2 were with and 1 was a years been described as a for listerial meningitis patients years in this as a at for listerial CNS infections, more than were years including all the patients with no reported No patient was at the of of listerial brain abscess. in patients with are in in patients with and listerial brain our there have been no previously reported cases of listerial brain abscess in cardiac transplant recipients. Listerial meningitis and bacteremia have been described in heart transplant and listerial meningitis been reported to following of for treatment of graft Listerial brain abscess was a rare complication in heart transplant at our the The listerial brain abscesses between 3 and 5 months after cardiac with 3 months to 6 years after transplant in this 3 cardiac transplant patients were taking immunosuppressive at the developed brain and 1 patient had a recent in for graft rejection. is that of the heart transplant was taking at the of or before the of listerial brain abscess. This antimicrobial have patients from infection by L. monocytogenes. been to be a antibiotic in and been found to be an therapy for listerial meningitis cardiac transplant is also an for the of infections due to and No data that the of in the of listerial infections in this patient to our At our institution, no cases of listerial brain abscess have in cardiac transplant January is to be the most common in patients with brain abscess from in all patients to a history (27). However, in our of listerial brain only a of patients of a before the The of headaches had no or of as nausea, and were more commonly seen The of focal neurologic on examination on the of the and commonly were present in of patients in this This is more common than in brain abscess from which is to be between and of cases (27). of the patients in the case had concomitant bacteremia of patients for blood were This is a laboratory in cases of brain abscesses caused by in about of patients The of concomitant bacteremia the that the development of listerial brain abscess is to (12), in to from adjacent and there have been no reported cases of listerial brain abscess from from an adjacent of infection. listerial are to the of as at and and The of brain abscess development after listerial bacteremia be by our This patient was a cardiac transplant presented to the hospital with a brain abscess and a perianal the at the of a previous perianal abscess. material from the abscess had and 2 months before admission, and the infection was antibiotic Since L. monocytogenes was also subsequently from this is that the perianal area had been by this from a and that the brain was a of listerial infection from This of is by the identical to of the L. monocytogenes from the brain abscess. Listerial brain abscess been associated with meningitis in as as of cases meningitis with positive CSF was present in of the patients in the present There was no CSF in these had of and in of the is that most patients in our lumbar of these patients had lumbar performed before the of brain abscess on brain imaging. However, patients clearly had CSF by or lumbar puncture after brain imaging revealed macroscopic ring-enhancing There is for brainstem and neurologic after lumbar puncture in patients which the from only 2 of the CSF to brain imaging were for Listeria 8 and and in these cases the blood cultures were also There were no of acute neurologic or to the of a lumbar puncture in this of the as the and the basal is more common with listerial brain abscess than with abscesses from causes or in of patients in this is that 6 of these 8 patients had concomitant of the of the abscesses. Two of these patients 12 and also had meningitis with positive CSF cultures for L. monocytogenes, 2 of from the This the development of meningitis in the 6 patients with concomitant in with abscesses cortical The that 5 of the 6 due to listerial brain abscess were with alone the of a early and of the brain abscess aspiration is suggested for abscesses for abscesses in brain cerebellum and and for of the to therapy (27). excision be for patients that antibiotic therapy or organisms. that to all reported listerial brain abscesses have been alone be a to treatment the of positive blood cultures for in the of for The most common antimicrobial regimen used in this was ampicillin an and all patients given this regimen 1 were This that the of ampicillin and gentamicin be the antibiotic regimen of for the treatment of listerial brain abscess. Ampicillin be for a of 4 weeks and gentamicin for is be a antibiotic for the treatment of this infection in patients to Brain abscess is a form of listerial central nervous system infection. We 5 patients with listerial brain including the first 3 cases of listerial brain abscess described in cardiac transplant and review 34 cases from the patients had including with The most common presenting symptoms were focal neurologic mental status changes, and fever. Blood cultures were commonly cerebrospinal fluid cultures were positive in only of patients presented with a brain and of the patients had were most commonly ampicillin an Six were to listerial brain abscess in this and of these patients had early patients were with of the patients required of the abscess. Listeria monocytogenes infection be included in the of patient with with a brain abscess. The central nervous system be the only of Listeria and the be in patient with focal neurologic signs, mental status changes, and Listeria monocytogenes treatment the early of a in addition to