Meningitis por Listeria: serie de casos en un hospital de tercer nivel y utilidad de las nuevas técnicas de diagnóstico microbiológico / Listeria meningitis: case series in a tertiary level hospital and the usefulness of new microbiological diagnostic techniques

Introducción: La meningitis por Listeria monocytogenes (MLM) es una entidad grave con complicaciones a corto plazo. La reacción de polimerasa en cadena (RPC) puede ayudar a mejorar su diagnóstico y pronóstico. Objetivos: Conocer las características de los pacientes diagnosticados de meningitis por L. monocytogenes en los últimos años, a través de diferentes métodos microbiológicos. Pacientes y Métodos: Serie de casos de pacientes adultos ingresados con MLM en el Hospital Clínico San Carlos, Madrid, España, durante doce años (2009-2021). Se describieron variables epidemiológicas, clínicas, microbiológicas, radiológicas y terapéuticas. Resultados: Se registraron doce pacientes con MLM (edad media 67,5 años, 75% varones). En ocho se obtuvo un cultivo positivo a L. monocytogenes. La RPC en líquido cefalorraquídeo (LCR) fue positiva en los dos casos en los que se realizó la prueba. El tratamiento dirigido en todos los casos fue ampicilina durante 21 días. Se registraron complicaciones en un cuarto de los casos. Del total de pacientes uno falleció. Conclusiones: La MLM es una enfermedad poco frecuente y de difícil diagnóstico. En nuestra serie de casos los dos pacientes diagnosticados por RPC tuvieron resultado de cultivo de LCR negativo, y presentaron buena evolución. La determinación de RPC podría permitir diagnosticar un mayor número de casos y con mayor precocidad.

Background: Listeria monocytogenes meningitis (LMM) is a serious entity with short-term complications. Polymerase chain reaction (PCR) can help to improve its diagnosis and prognosis. Aim: To know the characteristics of patients diagnosed with meningitis by L. monocytogenes in recent years, through different microbiological methods. Methods: Case series of adult patients admitted with LMM at the Hospital Clínico San Carlos of Madrid, Spain, during twelve years (2009-2021). Epidemiological, clinical, microbiological, radiological and therapeutic variables were described. Results: Twelve patients with LMM were recorded (mean age 67.5 years, 75% male). Eight had a positive culture for L. monocytogenes. cerebrospinal fluid (CSF) PCR was positive in the two cases in which the test was performed. Treatment in all cases was ampicillin for 21 days. Complications were recorded in a quarter of the cases. One patient died. Conclusions: LMM is a rare and difficult to diagnose disease. In our series of cases, the two patients diagnosed by PCR had negative CSF culture results, and presented good evolution. PCR determination could allow a greater number of cases to be diagnosed earlier.

High incidence of severe neurological manifestations and high mortality rate for adult Listeria monocytogenes meningitis in Taiwan.

The clinical characteristics and therapeutic outcomes of adult Listeria monocytogenes meningitis are not commonly examined in isolation in the literature. During a study period of 19 years (2000-2018), 366 patients with culture-proven adult bacterial meningitis (ABM) were identified in the author's hospital (264 patients in 2000-2010 and 102 patients in 2011-2018). Of the 366 ABM patients, 330 had monomicrobial infections while the other 36 had mixed infections. L. monocytogenes infection was identified in 11 of the 330 patients with monomicrobial ABM (3 in 2000-2010 and 8 in 2011-2018). These 11 patients included 5 males and 6 females, aged 47 to 76 years (median age = 61.7). None of the 11 patients had a postneurosurgical state as the underlying cause, but 3 of them contracted the infection nosocomially. Common underlying conditions included liver cirrhosis (4), systemic malignancy (3), diabetes mellitus (3), and renal disease (2). The most common clinical manifestations were fever (11), altered consciousness (8), seizure (8), bacteremia (7) and hydrocephalus (5). The therapeutic result revealed a mortality rate of 72.7% (8/11), but no significant prognostic factors were identified. The clinical features of 8 additional Taiwanese L. monocytogenes ABM patients reported in the literature, were also included for analysis. The present study revealed an increase in L. monocytogenes ABM in recent years and most patients presented with severe neurological manifestations. The current study is a preliminary overview of L. monocytogenes meningitis in adults and a further large-scale study is needed for improved delineation of this specific infectious syndrome.

The clinical course and outcome of Listeria monocytogenes meningitis: A retrospective single center study.

BACKGROUND: The aim of the study was to determine clinical manifestations and outcome of Listeria monocytogenes meningitis (LM) and to compare with other forms of bacterial meningitis (BM). MATERIAL AND METHODS: We analyzed records of all adult patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland. RESULTS: Out of 343 analyzed patients with BM 24 were diagnosed to have LM. Patients with LM were older compared to patients with other forms of BM (62 years vs. 57 years, p=0.039), were more likely to have cancer (16.7% vs. 4.7%, p=0.045), receive immunosuppressive treatment (45.8% vs. 10.7%, p<0.001), or be immunocompromised in any way (62.5% vs. 35.5%, p=0.016). Blood tests showed lower WBC (10.7 × 103 cells/µl vs. 15.5 × 103 cells/µl, p=0.004), C-reactive protein (150 mg/L vs. 221 mg/L, p=0,019) and procalcitonin (1.27 ng/mL vs. 3.78 ng/mL, p=0.003) in LM group. Analysis of cerebrospinal fluid showed lower cell count (531.5 cells/µL vs. 1100 cells/µL, p<0.001) and lower chloride (113 mmol/L vs. 117 mmol/L, p=0.036) in patients with LM. In the multiple logistic regression analysis, immunosuppressive therapy was the only variable independently associated with LM (OR:8.72, CI 95%:1.41-64.34, p=0.024). CONCLUSIONS: LM is associated with older age, cancer and immunosuppressive therapy. However, in multivariate analysis only immunosuppressive therapy turned out to be an independent risk factor for LM.

Epidemiology and treatment of the commonest form of listeriosis: meningitis and bacteraemia.

Listeria monocytogenes is a Gram-positive bacillus and facultative intracellular bacterium whose transmission occurs mainly through the consumption of contaminated food. Listeriosis has an incidence estimated at around three-six cases per million per year and the most common forms of the infection are neurolisteriosis, bacteraemia, and maternal-neonatal infection. Those affected by listeriosis are at the extremes age of the life or report specific risk factors, such as malignancies, causing a defect of cellular immunity. Patients with L. monocytogenes meningitis present with signs and symptoms similar to those reported in the general population with community-acquired bacterial meningitis, but can experience a longer prodromal phase. Instead, patients with bacteraemia present generally with a febrile illness without focal symptoms, or with influenza-like symptoms and diarrhoea. These aspecific findings make the diagnosis difficult in the population of patients at the highest risk such as cirrhotics or those receiving chemotherapy. Mortality rate is estimated around 20% with a significant increase among those reporting a delay in diagnosis and treatment and in those with severe comorbidity. A number of antibiotics have been demonstrated to be active against L. monocytogenes, but penicillin, amoxicillin, and ampicillin are those used with the highest frequency and suggested by current guidelines and expert opinions. These antibiotics bind to PBP-3 with high affinity and are stored in the cytosol when taken up by cells. Although amoxicillin appears to have a better activity than ampicillin on the basis of in vitro studies, ampicillin is currently the drug of choice for the treatment of listeriosis. Cotrimoxazole could be administered as an alternative treatment; its use is associated with a favourable outcome probably due to the favourable penetration with brain. Quinolones have an excellent tissue and cell penetration and are rapidly bactericidal, but their clinical activity is not as high as we can predict on the basis of experimental model. 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 as confirmed by a number of case-series highlighting its use as rescue therapy of pneumococcal meningitis, but data are currently limited particularly if we consider neurolisteriosis. Combination therapies have been proposed to enhance the activity of penicillins against Listeria in an attempt to achieve complete killing and decrease mortality. Steroids use is ineffective.

Community-acquired bacterial meningitis in adults with cancer or a history of cancer.

OBJECTIVES: To study the incidence, clinical presentation, causative bacteria, and outcome of community-acquired bacterial meningitis in adults with cancer. METHODS: We evaluated incidence and characteristics of patients with cancer included in a nationwide prospective cohort study of adults with community-acquired meningitis performed in the Netherlands from March 1, 2006, to September 31, 2014. All patients underwent a neurologic examination at hospital discharge, and outcome was graded using the Glasgow Outcome Scale. RESULTS: Active cancer was identified in 68 of 1,351 episodes (5%) and a history of cancer in 87 (6%). The annual incidence of community-acquired bacterial meningitis was 2.71-fold (95% confidence interval [CI] 1.68-4.36, p < 0.001) increased for patients with cancer compared to patients without cancer in 2010, and 3.52-fold (95% CI 2.16-5.73, p < 0.001) in 2013. The clinical presentation of bacterial meningitis in patients with cancer compared to patients without cancer was similar. Patients with active cancer presented with lower leukocyte count in blood (12.1 × 10(9) cells/L vs 17.3 × 10(9) cells/L, p < 0.001) and CSF (670 cells/mm(3) vs 2,567 cells/mm(3), p < 0.001) and were more likely to be infected with Listeria monocytogenes (21% vs 5%, p < 0.001) than patients without cancer. Active cancer was identified as an independent risk factor for unfavorable outcome in bacterial meningitis (odds ratio 1.85, 95% CI 1.09-3.13). CONCLUSIONS: One of 8 patients with community-bacterial meningitis was identified to have a history of cancer and cancer was considered active in half of these patients. Patients with active cancer present with lower CSF leukocyte counts, are more likely to be infected with L monocytogenes, and are at high risk of unfavorable outcome.

[Meningitis due to Listeria monocytogenes in adults]. / Meningitis por Listeria monocytogenes en adultos.

INTRODUCTION: Listeria monocytogenes is the third most common cause of community-acquired bacterial meningitis in adults. AIMS: To describe the characteristics of meningitis caused by Listeria (LM) in adults and to compare them with those of meningitis due to other causations (nLM). PATIENTS AND METHODS: A retrospective analysis of a series of hospital cases was conducted, including patients aged between ≥ 14 years diagnosed with LM in a referral hospital between 1982 and 2011. RESULTS: The study involves 16 cases of LM, 12.1% of the cases of community-acquired meningitis with an identified aetiology. Predisposing factors were age (mean of 65 versus 52 years; p = 0.019) and immunosuppression/comorbidity (62.5% versus 3.4%; p < 0.001), treatment with corticoids (37.5%) and chronic liver disease (25%) being the most frequent. The classical triads of acute bacterial meningitis, clinical features and analysis of the cerebrospinal fluid (CSF) were observed in 50 and 75% of the cases, respectively. Patients with LM presented lower leukocyte counts in CSF, a lower percentage of neutrophils, a greater frequency of lymphocytic pleocytosis and a lower frequency of Gram stain positive than those with nLM. The mortality rate was 12.5%, similar to that of patients with nLM. CONCLUSIONS: LM mainly affects patients who are immunosuppressed or with comorbidity, as well as elderly patients, although it may occur in the absence of risk factors. Clinically it does not differ from other causes of meningitis, but the initial CSF study may suggest it. Its mortality rate is similar to that of meningitis due to other aetiologies.

Long-term mortality in patients diagnosed with Listeria monocytogenes meningitis: a Danish nationwide cohort study.

OBJECTIVES: To determine the long-term mortality, the causes of death and the incidence of cancer in listeria meningitis patients. METHODS: Nationwide, population-based cohort study including all adult patients diagnosed with listeria meningitis from 1977 to 2006 and alive 1 year after diagnosis, and an age-and gender-matched, population control cohort. Kaplan-Meier tables, Cox regression analysis and cumulative incidence function were used as outcome analyses. RESULTS: We identified 114 listeria meningitis patients and 1026 population controls. The adjusted mortality rate ratio (MRR) for listeria meningitis patients the first 5 years of follow-up was 2.35(95% confidence interval (CI) 1.60-3.45) thereafter the MRR was 0.93(95% CI: 0.56-1.55). Listeria meningitis patients had an increased risk of death due to cancer the first 5 years of follow-up, and in the same period patients above 50 years of age had a 2-fold increased risk of being diagnosed with cancer, thereafter the risks declined to that of the background population. CONCLUSIONS: The long-term mortality in adult patients diagnosed with listeria meningitis was increased the first 5 years of follow-up, mainly due to death from cancer, thereafter the mortality did not differ from the background population. To improve survival this patient population should be meticulously screened for predisposing conditions, mainly underlying malignant diseases.

Infectious and non-infectious neurologic complications in heart transplant recipients.

Neurologic complications are important causes of morbidity and mortality in heart transplant (HT) recipients. New immunomodulating agents have improved survival rates, although some have been associated with a high rate of neurologic complications (infectious and non-infectious). We conducted this study to analyze the frequency of these complications, before and after the use of daclizumab induction therapy. We reviewed all neurologic complications in our HT cohort, comparing infectious with non-infectious complications over 2 periods of time in which different induction therapies were used (316 patients with OKT3 or antithymocyte globulin from 1988 to 2002, and 68 patients with daclizumab from 2003 to 2006). Neurologic complications were found in 75/384 patients (19.5%) with a total of 78 episodes. Non-infectious complications accounted for 68% of the 78 episodes of neurologic complications. A total of 51 patients and 53 episodes were detailed as follows: 25 episodes of stroke (25 of 78 total episodes, 32%; 19 ischemic, 6 hemorrhagic); 7 neuropathies; 6 seizures; 4 episodes of transient ischemic attack (TIA); 3 anoxic encephalopathy; 2 each brachial plexus palsy and metabolic encephalopathy; and 1 each myoclonia, central nervous system (CNS) lymphoma, subdural hematoma, and Cotard syndrome. Mean time to presentation of stroke, TIA, and encephalopathy was 1 day (range, 1-19 d) posttransplant. Mortality rate among non-infectious complications was 12/53 (22.6%). Infectious complications accounted for 32% of the 78 total episodes. We found 25 episodes in 24 patients: 17 herpes zoster (median, 268 d after HT), 3 CNS aspergillosis (median, 90 d after HT), 1 CNS toxoplasmosis and tuberculosis (51 d after HT), 1 pneumococcal meningitis (402 d after HT), and 2 Listeria meningitis (median, 108 d after HT). The 3 patients with CNS aspergillosis died. The mortality rate among patients with infectious neurologic complications was 12% (42.8% if the CNS was involved). When we compared the OKT3-ATG and daclizumab groups, we found that the incidence of non-infectious complications was 15.1% vs. 7.3%, respectively, and the incidence of infectious complications was 7.5% vs. 1.4%, respectively. All but 1 opportunistic infection occurred in the OKT3-ATG time period. In conclusion, a wide variety of neurologic complications affected 19.5% of HT recipients. Non-infectious causes clearly predominated, but infections still accounted for 32% of the episodes. New monoclonal induction therapies have contributed to diminished CNS opportunistic infections in our program.

Listeria meningitis in transplant recipients.

INTRODUCTION: Meningitis is a rare complication following organ and stem-cell transplantation and can be caused by a variety of microorganisms. AIM: To retrospectively review the clinical course and outcome of five cases of listeriosis in four organ recipients and one stem-cell recipient during a seven-year period. PATIENTS AND METHODS: Patient records for more than 3500 patients undergoing organ or stem-cell transplantation at the university hospital of Innsbruck during a 27-year period were evaluated. Standard immunosuppression consisted of calcineurin inhibitor-based triple drug therapy with or without ATG or IL2 receptor antagonist induction. RESULTS: The first case affected a 35-year-old woman who received an allogenic bone marrow transplant for advanced breast cancer. Cases two and three related to two male heart recipients. Cases four and five were diagnosed in one male and one female renal recipient. Listeria monocytogenes was isolated from blood in two cases and from cerebrospinal fluid in three. Treatment consisted of ampicillin in all cases with the addition of tobramycin (1), TMPS (1), meropenem (2) or imipenem/cilastatin (1). The deaths of two patients were directly related to L. monocytogenes. CONCLUSIONS: Although listeriosis is a rare complication following transplantation, this infection should be ruled out in individuals presenting with neurological symptoms and fever.

[Cerebromeningeal listeriosis associated with a cytolytic hepatitis. First case report in Senegal]. / Listériose cérébro-méningée associée à une hépatite cytolytique. A propos de la première observation sénégalaise.

Hepatitis due to Listeria monocytogenes is uncommon in adults. This report describes the first case observed in Senegal. The patient was a 73-year old man presenting listeria-related hepatitis presumably secondary to low-grade meningeal encephalitis. Treatment using ampicillin was unsuccessful and the patient died four days after hospitalization. The authors note that the incidence of adult listeriosis has risen constantly for the past twenty years in relation with alcohol abuse, cirrhosis, diabetes, kidney insufficiency, cancer, AIDS, and organ transplantation. However no predisposing factors were observed in the present case.

Surto de meningite neonatal por listeria monocytogenes / An outbreak of listeria monocytogenes meningitis in neonates

Listeria monocytogenes, um bacilo Gram-positivo, asporogênico, tem sido isolada de mamíferos, aves, peixes, crustáceos e insetos, sendo seu habitat primário, o solo e vegetal em decomposiçäo. Causa infecçäo no homem e animais domésticos. Em humanos ocorre em maior incidência em recém-nascidos e indivíduos acima de 60 anos, sendo a meningite uma manifestaçäo comum de listeriose. De cinco crianças recém-nascidas no mesmo Centro Obstérico de um hospital da Grande Säo Paulo, foi isolada Listeria monocytogenes do líquido cefalorraquidiano (LCR). Todas as cepas pertenceram ao mesmo sorotipo, L4b. Foi analisada a resistência destas cepas a antibacterianos. As mäes de 6 crianças nascidas no período de 14.05 horas, das quais uma foi óbito sem ter sido puncionado o LCR, tiveram colhidas fezes e urina. Destes materiais näo foi isolado o microrganismo

[Listeriosis in the nonpregnant adult during an epidemic outbreak on Grand Canary]. / Listeriosis en el adulto no gestante durante un brote epidémico en Gran Canaria.

Twenty-two cases of community-acquired epidemic listeriosis were recorded from December 31st, 1991, to May 15th, 1993, at the Nuestra Señora del Pino Hospital, Las Palmas. The incidence during this outbreak was 31 times higher than the corresponding incidence in the last few years. Twelve cases occurred in pregnant women and/or neonates and ten in non-pregnant adult individuals. Our aim was to study the clinical, biological, radiological, and evolutive issues in non-pregnant adult patients. Six patients had some immunosuppressive condition: cancer, chemotherapy, AIDS, diabetes, and alcoholism. Eight patients had documented involvement of central nervous system: 6 cases of meningitis and 3 of cerebritis (one case had both meningitis and cerebritis); in the remaining two patients associated with seizures and acute confusional states, respectively. A neurological involvement was not documented because of the fulminant clinical course. CSF examination revealed mononuclear predominance in half of meningitis cases and was normal in two of the three cerebritis cases. The mean time from admission to diagnosis was 3.5 days. All patients but the two who died in the first hours of the disease received ampicillin and an aminoglycoside. The response to therapy was excellent with exception of one patient with meningitis who died in the fourth day of therapy. The clustering of listeriosis cases should alert physicians about the possibility of an epidemic outbreak. Listeria infection in non-pregnant adult individuals in this outbreak showed a high rate of neurological involvement, with focal cerebritis and pleocytosis with a mononuclear predominance in meningitis.

Risk factors for listeriosis in Denmark, 1989-1990.

Dietary risk factors for listeriosis were examined, and the risk levels of listeriosis according to specific underlying diseases were evaluated, in order to study the basis for prevention. Questionnaires from 50 listeriosis patients and 40 matching control persons were analysed. Unpasteurized milk was a risk food for sporadic listeriosis, and an outbreak of a European epidemic strain of Listeria monocytogenes was obviously linked to a blue-mould cheese or a hard cheese. Leukaemia, AIDS and renal transplantation were found to be associated with > 1000-fold risk of acquiring listeriosis, compared with healthy persons. As a part of prevention, persons running a high risk of contracting listeriosis should be individually informed about food hygiene and risk foods.

Listeria meningitis after bone marrow transplantation.

Over the past decade infections from food-borne Listeria monocytogenes have become an important cause of septicaemia and meningitis and immunocompromised patients are at particular risk. We report three cases of Listeria meningitis occurring post-BMT. The patients were aged 53, 51 and 56 years and presented 4, 7 and 90 months post-transplant, respectively. The first patient had undergone allogeneic BMT for myelodysplasia and the other two patients had ABMT for AML in second and first CR, respectively. All the patients presented with classical features of meningitis and L. monocytogenes was cultured from cerebrospinal fluid. All made a full recovery with appropriate antibiotic therapy. We have not seen cases of meningitis due to other organisms in our transplant programme and the cases represent a risk of one episode per 59 surviving patient years. None of the patients was receiving prophylactic post-BMT antibiotics and the episodes may strengthen the case for using prophylactic penicillin. Recent epidemics of septicaemia and meningitis caused by L. monocytogenes-contaminated milk and cheese suggest that these patients should be informed about potential sources of infection.

[Human listeriosis infections in West Germany, 1969-1985]. / Menschliche Listeriose-Erkrankungen in der Bundesrepublik Deutschland, 1969-1985.

296 strains of Listeria monocytogenes have been submitted for confirmation and further studies to the Listeria Reference Laboratory at the Institute of Hygiene in Würzburg, Federal Republic of Germany. They have been isolated between 1969 and 1985 from human cases in the Federal Republic and West Berlin. The results of an analysis of the respective cases are presented here on the basis of questionnaires. A steady increase of Listeria isolations has been noted during the past few years. The largest number of strains originated from the district Nordrhein-Westfalen which has the largest population of all German federal districts. The highest incidence calculated from the number of strains and total population was found for the district of Saarland. There was no predominance detectable of listeriosis among the rural population. 60% of the strains came from patients living in urban areas. In 6 out of 21 cases of neonatal listeriosis at least one of the parents was engaged in professional medical services. The most frequently observed clinical entities were meningitis (41.14%) and septicaemia (36.00%). Among the newborns septicaemia was predominant with 40.90%. Listeriosis during pregnancy and among newborns was connected with 53.57% of all strains isolated. The questionnaire revealed for the underlying conditions in 35% and in 24% of cases malignancies and organ transplantations, respectively. There was no increased rate of predominance found among the elderly. However, 50% of all strains isolated originated from newborns. The sex distribution was almost equal; 52.56% from males of the total number of isolates and 51.22% from males among the newborns. 67% of these which had a meningitis after the first weeks of life were male. There was no seasonal incidence detectable. Serovar 4b was found in 66.22% of all isolates tested. 295 strains produced acid from rhamnose and alpha-methyl-d-mannose, but not from d-xylose and were thus typical for L. monocytogenes. One strain needs further studies.

Listeria meningitis: report of ten recent cases and review of current therapeutic recommendations.

Ten cases of meningitis due to Listeria monocytogenes were admitted to three hospitals in Berlin between 1978 and 1983. One patient was a premature infant in whom meningitis was diagnosed as part of typical granulomatosis infantiseptica. Another presented with signs of brainstem encephalitis which was confirmed post mortem. Positive blood cultures were obtained from five of the patients. Two strains of listeria were resistant and one was only moderately sensitive to penicillin. The three most recently isolated strains were tested for sensitivity to the third generation cephalosporins. All were resistant to latamoxef, and two were resistant to cefotaxime. The implications of these findings for the empirical treatment of purulent meningitis are discussed.

Clinical aspects on 64 cases of juvenile and adult listeriosis in Sweden.

In 1958-74 altogether 64 cases of bacteriologically verified infections of Listeria monocytogenes were diagnosed in Sweden in children, aged more than 27 days, and in adults. Immunosuppression predisposed to the disease. Thus, many patients had co-existing disorders, such as leukemia and alcoholism. Sixteen patients had been treated with corticosteroids, which were combined with cytostatic drugs in nine. Meningoencephalitis was diagnosed in 52 patients and was fatal in 16. The clinical symptoms did not differ from those in purulent meningitis caused by other bacteria. In the cerebrospinal fluid the cellular response was dominated by polymorphonuclear cells in 29 patients and by mononuclear cells in 20. Ten patients had septicemia, which was fatal in four. Clinical symptoms were dominated by chills, high fever and general prostration. One patient had pleurisy and one an abscess of the neck; both recovered. Serotypes 1 and 4b prevailed and were equally common. Many patients developed raised antibody titers in both the O-agglutination test and the complement fixation test. The titers were often not positive until after a month. Moderate granulocytosis was the rule and monocytosis was rarely seen. Ampicillin alone or combined with an aminoglycoside seemed to be the drug of choice in the treatment of listeriosis. An alternative drug was tetracycline. Most deaths occurred within six days of onset of the illness. Early diagnosis and treatment were imperative. Most patients recovered and serious sequelae were rare.

Central nervous system infections in patients with cancer. Changing patterns.

Central nervous system infections in patients with cancer at Memorial Sloan-Kettering Cancer Center from 1971 to 1974 were surveyed and compared with a previous survey from 1955 to 1970. The two periods were similar in that: 1) There was a high incidence of CNS infection in patients with lymphoma, leukemia, and head and spine tumors, 2) specific organisms tended to infect patients with certain primary neoplasms, and 3) fungal infections were common and difficult to diagnose. The two periods differed in that: 1) the overall incidence of CNS infection was lower in 1971 to 1974, 2) there was a decreased incidence of cryptococcal meningitis, and 3) there was an increase in Listeria monocytogenes meningitis. Early recognition of CNS infection and aggressive therapy appears to increase survival.