IASR 39(6), 2018【特集】無菌性髄膜炎患者からのウイルスの検出、2017年末現在 [Internet]. [cited 2020 Jan 20]. Available from: https://www.niid.go.jp/niid/ja/viral-megingitis-m/viral-megingitis-iasrtpc/8085-460t.html
McGill F, Griffiths MJ, Bonnett LJ, Geretti AM, Michael BD, Beeching NJ, McKee D, Scarlett P, Hart IJ, Mutton KJ, Jung A, Adan G, Gummery A, Sulaiman WAW, Ennis K, Martin AP, Haycox A, Miller A, Solomon T; UK Meningitis Study Investigators.
Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study.
Lancet Infect Dis. 2018 Sep;18(9):992-1003. doi: 10.1016/S1473-3099(18)30245-7. Epub 2018 Jun 29.
Abstract/Text
BACKGROUND: Viral meningitis is increasingly recognised, but little is known about the frequency with which it occurs, or the causes and outcomes in the UK. We aimed to determine the incidence, causes, and sequelae in UK adults to improve the management of patients and assist in health service planning.
METHODS: We did a multicentre prospective observational cohort study of adults with suspected meningitis at 42 hospitals across England. Nested within this study, in the National Health Service (NHS) northwest region (now part of NHS England North), was an epidemiological study. Patients were eligible if they were aged 16 years or older, had clinically suspected meningitis, and either underwent a lumbar puncture or, if lumbar puncture was contraindicated, had clinically suspected meningitis and an appropriate pathogen identified either in blood culture or on blood PCR. Individuals with ventricular devices were excluded. We calculated the incidence of viral meningitis using data from patients from the northwest region only and used these data to estimate the population-standardised number of cases in the UK. Patients self-reported quality-of-life and neuropsychological outcomes, using the EuroQol EQ-5D-3L, the 36-Item Short Form Health Survey (SF-36), and the Aldenkamp and Baker neuropsychological assessment schedule, for 1 year after admission.
FINDINGS: 1126 patients were enrolled between Sept 30, 2011, and Sept 30, 2014. 638 (57%) patients had meningitis: 231 (36%) cases were viral, 99 (16%) were bacterial, and 267 (42%) had an unknown cause. 41 (6%) cases had other causes. The estimated annual incidence of viral meningitis was 2·73 per 100 000 and that of bacterial meningitis was 1·24 per 100 000. The median length of hospital stay for patients with viral meningitis was 4 days (IQR 3-7), increasing to 9 days (6-12) in those treated with antivirals. Earlier lumbar puncture resulted in more patients having a specific cause identified than did those who had a delayed lumbar puncture. Compared with the age-matched UK population, patients with viral meningitis had a mean loss of 0·2 quality-adjusted life-years (SD 0·04) in that first year.
INTERPRETATION: Viruses are the most commonly identified cause of meningitis in UK adults, and lead to substantial long-term morbidity. Delays in getting a lumbar puncture and unnecessary treatment with antivirals were associated with longer hospital stays. Rapid diagnostics and rationalising treatments might reduce the burden of meningitis on health services.
FUNDING: Meningitis Research Foundation and UK National Institute for Health Research.
Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
Petersen PT, Bodilsen J, Jepsen MPG, Larsen L, Storgaard M, Hansen BR, Helweg-Larsen J, Wiese L, Lüttichau HR, Andersen CØ, Nielsen H, Brandt CT; Danish Study Group of Infections of the Brain (DASGIB).
Clinical features and prognostic factors in adults with viral meningitis.
Brain. 2023 Sep 1;146(9):3816-3825. doi: 10.1093/brain/awad089.
Abstract/Text
Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.
© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.
Kupila L, Vuorinen T, Vainionpää R, Hukkanen V, Marttila RJ, Kotilainen P.
Etiology of aseptic meningitis and encephalitis in an adult population.
Neurology. 2006 Jan 10;66(1):75-80. doi: 10.1212/01.wnl.0000191407.81333.00.
Abstract/Text
OBJECTIVE: To investigate the etiology of aseptic meningitis and encephalitis in an adult population using modern microbiologic methods.
METHODS: Consecutive patients (ages > or =16) with aseptic meningitis or encephalitis treated in Turku University Hospital, Finland, during 1999 to 2003 were included in the study. Microbiologic tests were performed, including CSF PCR tests for enteroviruses, herpes simplex virus (HSV) 1, HSV-2, and varicella zoster virus (VZV), as well as serum and CSF antibody analysis for these viruses. Antibody testing was also performed for other pathogens commonly involved in neurologic infections. Virus culture was performed on CSF, fecal, and throat swab specimens.
RESULTS: Etiology was defined in 95 of 144 (66%) patients with aseptic meningitis. Enteroviruses were the major causative agents (26%), followed by HSV-2 (17% of all, 25% of females) and VZV (8%). Etiology was identified in 15 of 42 (36%) patients with encephalitis, VZV (12%), HSV-1 (9%), and tick-borne encephalitis virus (9%) being the most commonly involved pathogens. Etiologic diagnosis was achieved by PCR in 43% of the patients with meningitis and in 17% of those with encephalitis.
CONCLUSIONS: Enteroviruses and HSV-2 are the leading causes of adult aseptic meningitis, and PCR is of diagnostic value. However, in most cases of encephalitis, the etiology remains undefined.
Uchihara T, Tsukagoshi H.
Jolt accentuation of headache: the most sensitive sign of CSF pleocytosis.
Headache. 1991 Mar;31(3):167-71. doi: 10.1111/j.1526-4610.1991.hed3103167.x.
Abstract/Text
We prospectively examined the clinical signs of 54 febrile patients associated with recent-onset headache. They underwent lumbar puncture (LP) on suspicion of meningitis. The relation of each sign to cerebrospinal fluid (CSF) pleocytosis was estimated. Among 34 patients with pleocytosis, 33 had jolt accentuation (sensitivity: 97.1%), while only 5 of them had neck stiffness or Kernig's sign. Among 20 patients without pleocytosis, 12 had no jolt accentuation (specificity: 60%). We found jolt accentuation to be the most sensitive sign of CSF pleocytosis. If jolt accentuation is noted in a febrile patient associated with recent onset headache, the CSF should be examined even in the absence of neck stiffness or Kernig's sign.
Viallon A, Zeni F, Lambert C, Pozzetto B, Tardy B, Venet C, Bertrand JC.
High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis.
Clin Infect Dis. 1999 Jun;28(6):1313-6. doi: 10.1086/514793.
Abstract/Text
It was shown in children that serum procalcitonin was the best marker to use to differentiate bacterial from viral meningitis. To evaluate procalcitonin in the diagnosis of acute bacterial and viral meningitis, we conducted a prospective study including adult patients who were suspected of having meningitis and who were admitted to an emergency department. Cerebrospinal fluid (CSF) and serum levels of procalcitonin were measured in 105 consecutive patients. The diagnosis of meningitis was based on clinical findings, gram staining, culture, and chemical analysis of CSF. Twenty-three patients had bacterial meningitis, 57 had viral meningitis, and 25 did not have meningitis. Bacteriologic and chemical analysis of CSF did not allow correct differentiation of viral from bacterial meningitis. On the other hand, a serum procalcitonin level >0.2 ng/mL had a sensitivity and specificity of up to 100% in the diagnosis of bacterial meningitis. Serum procalcitonin levels seem to be the best marker in differentiating between bacterial and viral meningitis in adults.
Dubos F, Korczowski B, Aygun DA, Martinot A, Prat C, Galetto-Lacour A, Casado-Flores J, Taskin E, Leclerc F, Rodrigo C, Gervaix A, Leroy S, Gendrel D, Bréart G, Chalumeau M.
Serum procalcitonin level and other biological markers to distinguish between bacterial and aseptic meningitis in children: a European multicenter case cohort study.
Arch Pediatr Adolesc Med. 2008 Dec;162(12):1157-63. doi: 10.1001/archpedi.162.12.1157.
Abstract/Text
OBJECTIVE: To validate procalcitonin (PCT) level as the best biological marker to distinguish between bacterial and aseptic meningitis in children in the emergency department.
DESIGN: Secondary analysis of retrospective multicenter hospital-based cohort studies.
SETTING: Six pediatric emergency or intensive care units of tertiary care centers in 5 European countries.
PARTICIPANTS: Consecutive children aged 29 days to 18 years with acute meningitis.
MAIN OUTCOME MEASURES: Univariate analysis and meta-analysis to compare the performance of blood parameters (PCT level, C-reactive protein level, white blood cell count, and neutrophil count) and cerebrospinal fluid parameters (protein level, glucose level, white blood cell count, and neutrophil count) quickly available in the emergency department to distinguish early on between bacterial and aseptic meningitis.
RESULTS: Of 198 patients analyzed, 96 had bacterial meningitis. Sensitivity of cerebrospinal fluid Gram staining was 75%. The PCT level had significantly better results than the other markers for area under the receiver operating characteristic curve (0.98; 95% confidence interval, 0.95-0.99; P = .001). At a 0.5-ng/mL threshold, PCT level had 99% sensitivity (95% confidence interval, 97%-100%) and 83% specificity (95% confidence interval, 76%-90%) for distinguishing between bacterial and aseptic meningitis. The diagnostic odds ratio between high PCT level and bacterial meningitis was 139 (95% confidence interval, 39-498), without significant heterogeneity between centers.
CONCLUSIONS: The PCT level is a strong predictor for distinguishing between bacterial and aseptic meningitis in children in the emergency department. Its combination with other parameters in an effective clinical decision rule could be helpful.
Dubos F, Moulin F, Gajdos V, De Suremain N, Biscardi S, Lebon P, Raymond J, Breart G, Gendrel D, Chalumeau M.
Serum procalcitonin and other biologic markers to distinguish between bacterial and aseptic meningitis.
J Pediatr. 2006 Jul;149(1):72-6. doi: 10.1016/j.jpeds.2006.02.034.
Abstract/Text
OBJECTIVE: To identify the biologic tests that best distinguish between bacterial and aseptic meningitis in an emergency department (ED).
STUDY DESIGN: All children hospitalized for bacterial meningitis between 1995 and 2004 or for aseptic meningitis between 2000 and 2004 were included in a retrospective cohort study. Predictive values of blood (C-reactive protein, procalcitonin [PCT], white blood cell [WBC] count, neutrophil count) and cerebrospinal fluid (CSF) findings (protein, glucose, WBC count, neutrophil count) available in the ED were determined. Tests with the best predictive value were identified by using univariate and multivariate analyses and ROC curves comparison.
RESULTS: Among the 167 patients included, 21 had bacterial meningitis. The CSF gram-stain and bacterial antigen test had 86% and 60% sensitivity rates, respectively. PCT (>/=0.5 ng/mL) and CSF protein (>/=0.5 g/L) were the best biologic tests, with 89% and 86% sensitivity rates, 89% and 78% specificity rates, adjusted odds ratios of 108 (95% CI, 15-772) and 34 (95% CI, 5-217), and areas under the ROC curves of 0.95 and 0.93, respectively.
CONCLUSION: PCT and CSF protein had the best predictive value to distinguish between bacterial and aseptic meningitis in children.
Tanner DC, Weinstein MP, Fedorciw B, Joho KL, Thorpe JJ, Reller L.
Comparison of commercial kits for detection of cryptococcal antigen.
J Clin Microbiol. 1994 Jul;32(7):1680-4. doi: 10.1128/jcm.32.7.1680-1684.1994.
Abstract/Text
Although kits to detect cryptococcal antigen are used widely to diagnose cryptococcal infection, the comparative performance of commercially available assays has not been evaluated in the past decade. Therefore, we compared the sensitives and specificities of five commercially available kits for detecting cryptococcal antigen (four latex agglutination test kits--Calas [Meridian Diagnostics])--Crypto-LA [International Biological Labs], Myco-Immune [MicroScan], and Immy [Immunomycologics]--and an enzyme immunoassay kit, Premier [Meridian Diagnostics]) with culture for the diagnosis of cryptococcal meningitis and fungemia. Of 182 cerebrospinal fluid (CSF) and 90 serum samples submitted for cryptococcal antigen and fungal culture, 49 (19 and 30 samples, respectively) from 20 patients had a culture positive for Cryptococcus neoformans. For CSF specimens, the sensitivities and specificities of all kits were comparable (sensitivity, 93 to 100%; specificity, 93 to 98%). There was a significant difference in sensitivities of the kits when serum samples were tested with the International Biological Labs and MicroScan kits, which do not pretreat serum with pronase. These kits were less sensitive (sensitivity, 83%) than the Immy and Meridian latex kits (sensitivity, 97%), which do pretreat with pronase. The sensitivity of the Meridian enzyme immunoassay kit was comparable to that of the pronase-containing latex kits. These kits were of equivalent specificities (93 to 100%) when testing serum. Some of the currently available kits have limitations that need to be recognized for proper interpretation of results. Specifically, the use of pronase on serum samples reduces the number of false-positive results, and a titer of < or = 1:4 can be a false-positive result when CSF samples are being tested.
Ray B, Rylance G.
QUESTION 1. Normal CSF: does it exclude meningitis?
Arch Dis Child. 2009 Dec;94(12):988-91. doi: 10.1136/adc.2009.163766.
Abstract/Text
Sakushima K, Hayashino Y, Kawaguchi T, Jackson JL, Fukuhara S.
Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: a meta-analysis.
J Infect. 2011 Apr;62(4):255-62. doi: 10.1016/j.jinf.2011.02.010. Epub 2011 Mar 5.
Abstract/Text
OBJECTIVES: Cerebrospinal fluid (CSF) lactate is produced by bacterial anaerobic metabolism and is not affected by blood lactate concentration, an advantage over CSF glucose in differentiating bacterial meningitis from aseptic meningitis. However, the previous investigations have shown mixed results of the sensitivity and specificity. Our study's purpose was to assess the utility of CSF lactate in differentiating bacterial meningitis from aseptic meningitis.
METHODS: We searched MEDLINE and EMBASE for clinical studies that included CSF lactate measurement in bacterial meningitis and aseptic meningitis. Test characteristics were pooled using hierarchical summary ROC curve and random effects model.
RESULTS: Thirty three studies were included. The pooled test characteristics of CSF lactate were sensitivity 0.93 (95% CI: 0.89-0.96), specificity 0.96 (95% CI: 0.93-0.98), likelihood ratio positive 22.9 (95% CI: 12.6-41.9), likelihood ratio negative 0.07 (95% CI: 0.05-0.12), and diagnostic odds ratio 313 (95% CI: 141-698). Pretreatment with antibiotics lowered the sensitivity 0.49 (95% CI: 0.23-0.75). CSF lactate of around 35 mg/dl (34-36 mg/dl) had higher sensitivity and specificity than those of around 27 mg/dl (26-28 mg/dl).
CONCLUSIONS: CSF lactate's high negative likelihood ratio may make it useful for ruling out bacterial meningitis though pretreatment with antibiotics reduces clinical accuracy. CSF lactate of 35 mg/dl could be optimal cut-off value for distinguishing bacterial meningitis from aseptic meningitis.
Copyright © 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Schmidt H, Heimann B, Djukic M, Mazurek C, Fels C, Wallesch CW, Nau R.
Neuropsychological sequelae of bacterial and viral meningitis.
Brain. 2006 Feb;129(Pt 2):333-45. doi: 10.1093/brain/awh711. Epub 2005 Dec 19.
Abstract/Text
Survivors of meningitis often complain about neurological and neuropsychological consequences. In this study, the extent of these sequelae was quantified and correlated to MRI findings. Neurological, neuropsychological and neuroradiological examinations were performed with adult patients younger than 70 years, 1-12 years after recovery from bacterial meningitis (BM; n = 59), or from viral meningitis (VM; n = 59). Patients with other potential causes for neuropsychological deficits (e.g. alcoholism) were carefully excluded. Patients were compared to 30 healthy subjects adjusted for age, gender and length of school education. With the exception of attention functions, both patient groups showed more frequently pathological results than the control group for all domains examined. Applying an overall cognitive sum score, patients after BM did not differ significantly in their performance from patients after VM. Separate analyses of various cognitive domains, however, revealed a higher rate of persistent disturbances in short-term and working memory after BM than after VM. Moreover, patients after BM exhibited greater impairment of executive functions. Associative learning of verbal material was also reduced. These deficits could not be ascribed to impaired alertness functions or decreased motivation in BM patients. Applying a logistic regression model, the neuropsychological outcome was related to the neurological outcome. Patients with a Glasgow Outcome Scale (GOS) of <5 had more frequently impaired test results for non-verbal learning and memory. GOS was also correlated with performance in executive functions. Brain volume was lower and ventricular volume was higher in the bacterial than in the VM group, and cerebral volume and the amount of white matter lesions of patients after BM were negatively correlated with short-term and working memory. In conclusion, patients after both BM and VM with favourable outcome showed affected learning and memory functions. More patients after BM than after VM displayed pathological short-term and working memory. BM resulted in poorer performance in executive functions, language, short-term memory and verbal learning/memory tests. As a result of neurological and neuropsychological sequelae, BM with a GOS > or = 4 led to decreased activities of daily living but only a minority of patients were disabled in a way that social functions were affected. The extent of neuropsychological sequelae of BM might have been overestimated in earlier studies which often had not been controlled for comorbidity factors such as alcoholism.
Aronin SI, Peduzzi P, Quagliarello VJ.
Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing.
Ann Intern Med. 1998 Dec 1;129(11):862-9. doi: 10.7326/0003-4819-129-11_part_1-199812010-00004.
Abstract/Text
BACKGROUND: Community-acquired bacterial meningitis causes substantial morbidity and mortality in adults.
OBJECTIVE: To create and test a prognostic model for persons with community-acquired bacterial meningitis and to determine whether antibiotic timing influences clinical outcome.
DESIGN: Retrospective cohort study; patients were divided into derivation and validation samples.
SETTING: Four hospitals in Connecticut.
PATIENTS: 269 persons who, between 1970 and 1995, had community-acquired bacterial meningitis microbiologically proven by a lumbar puncture done within 24 hours of presentation in the emergency department.
MEASUREMENTS: Baseline clinical and laboratory features and times of arrival in the emergency department, performance of lumbar puncture, and administration of antibiotics. The target end point was the development of an adverse clinical outcome (death or neurologic deficit at discharge).
RESULTS: For the total group, the hospital mortality rate was 27%. Fifty-six of 269 patients (21 %) developed a neurologic deficit, and in 9% the neurologic deficit persisted at discharge. Three baseline clinical features (hypotension, altered mental status, and seizures) were independently associated with adverse clinical outcome and were used to create a prognostic model from the derivation sample. The prediction accuracy of the model was determined by using the concordance index (c-index). For both the derivation sample (c-index, 0.73 [95% CI, 0.65 to 0.81]) and the validation sample (c-index, 0.81 [CI, 0.71 to 0.92]), the model predicted adverse clinical outcome significantly better than chance. For the total group, the model stratified patients into three prognostic stages: low risk for adverse clinical outcome (9%; stage I), intermediate risk (33%; stage II), and high risk (56%; stage III) (P=0.001). Adverse clinical outcome was more common for patients in whom the prognostic stage advanced from low risk (P=0.008) or intermediate risk (P=0.003) at arrival in the emergency department to high risk before administration of antibiotics.
CONCLUSIONS: In persons with community-acquired bacterial meningitis, three baseline clinical features of disease severity predicted adverse clinical outcome and stratified patients into three stages of prognostic severity. Delay in therapy after arrival in the emergency department was associated with adverse clinical outcome when the patient's condition advanced to the highest stage of prognostic severity before the initial antibiotic dose was given.
Auburtin M, Wolff M, Charpentier J, Varon E, Le Tulzo Y, Girault C, Mohammedi I, Renard B, Mourvillier B, Bruneel F, Ricard JD, Timsit JF.
Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study.
Crit Care Med. 2006 Nov;34(11):2758-65. doi: 10.1097/01.CCM.0000239434.26669.65.
Abstract/Text
OBJECTIVE: To identify factors associated with mortality and morbidity among adults admitted to intensive care units (ICUs) for pneumococcal meningitis, particularly the impact of delayed antibiotic administration.
DESIGN: We conducted a prospective, multicenter, observational study of 156 consecutive adults hospitalized for pneumococcal meningitis. We analyzed parameters associated with 3-month survival.
SETTING: Fifty-six medical and medical-surgical ICUs in France.
INTERVENTION: None.
RESULTS: Of the 148 strains isolated, 56 (38%) were nonsusceptible to penicillin G. At 3 months after ICU admission, the mortality rate was 33% (51/156), and 34% of survivors (36/105) had neurologic sequelae. Multivariate analysis identified three variables as independently associated with 3-month mortality: Simplified Acute Physiology Score II (odds ration [OR], 1.12; 95% confidence interval [CI], 1.072-1.153; p = .002); isolation of a nonsusceptible strain (OR, 6.83; 95% CI, 2.94-20.8; p < 10(-4)), and an interval of >3 hrs between hospital admission and administration of antibiotics (OR, 14.12; 95% CI, 3.93-50.9; p < 10(-4)). In contrast, a cerebrospinal fluid leukocyte count >10(3) cells/microL had a protective effect (OR, 0.30; 95% CI, 0.10-0.944; p = 0.04).
CONCLUSIONS: Independent of severity at the time of ICU admission, isolation of penicillin-nonsusceptible strains and a delay in antibiotic treatment following admission were predictors of mortality among patients with pneumococcal meningitis.
Lepur D, Barsić B.
Community-acquired bacterial meningitis in adults: antibiotic timing in disease course and outcome.
Infection. 2007 Jun;35(4):225-31. doi: 10.1007/s15010-007-6202-0. Epub 2007 Jul 23.
Abstract/Text
OBJECTIVES: Despite improvements in diagnostic and therapeutic approach to adult patients with bacterial meningitis, the overall mortality rate is still high. The aim of this study was to evaluate antibiotic timing in the course and outcome of bacterial meningitis.
METHODS: Two hundred and eighty six patients with community-acquired bacterial meningitis aged 14 years and more were included in this retrospective cohort study. Observational period was between 1 January 1990 and 31 December 2004. To assess the association of antibiotic timing and disease outcome we analyzed three timing periods (according to the onset of disease, onset of consciousness disturbance and the time of admission to hospital). Analysis was also performed in a subgroup of culture positive meningitis in 176 patients with altered mental status.
RESULTS: Unfavorable outcome was found in 125 (43,7%) patients. In this group, the start of appropriate antibiotic treatment in relation to the onset of first symptoms and particularly to the onset of consciousness disturbance was significantly delayed (p = 0.018 and p < 0.001, respectively) compared to the favorable group. Logistic regression analysis in a subgroup of culture positive meningitis in patients with altered mental status revealed that early adequate antibiotic treatment related to the onset of overt signs of meningitis was independently associated with favorable outcome (OR = 11.19; 95% CI 4.37-32.57; p < 0.001). Advanced age, lower GCS and seizures (OR = 1.05, OR = 1.45 and OR = 3.65, respectively) were other risk factors of poor outcome. The presence of chronic diseases, pneumococcal etiology and clinical and laboratory variables which are indicators of disease severity (renal and/or liver dysfunction, hypotension and low cerebrospinal fluid glucose) were not confirmed as independent risk factors of poor outcome.
CONCLUSIONS: Our study emphasizes the importance of early and adequate antibiotic treatment in the management of bacterial meningitis which significantly enhances the chances for favorable outcome.
Proulx N, Fréchette D, Toye B, Chan J, Kravcik S.
Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis.
QJM. 2005 Apr;98(4):291-8. doi: 10.1093/qjmed/hci047. Epub 2005 Mar 10.
Abstract/Text
BACKGROUND: Bacterial meningitis continues to cause high mortality. Few studies address the possible association between this mortality and antibiotic administration delays.
AIM: To determine whether delays in antibiotic administration are associated with mortality from bacterial meningitis, and to identify inappropriate diagnostic-treatment sequences leading to such delays.
DESIGN: Retrospective case record study.
METHODS: We reviewed 123 cases of adult acute bacterial meningitis in 119 patients aged >/=16 years admitted to hospital from January 1990 to March 2002, using multivariate regression analysis to assess the association between meningitis mortality and door-to-antibiotic time (the time elapsed between emergency room presentation and antibiotics administration).
RESULTS: The case fatality rate was 13% (16/123). Adjusted odds ratios (OR) for mortality were: 8.4 (95%CI 1.7-40.9) for door-to-antibiotic time >6 h; 39.4 (95%CI 4.3-358.1) for afebrility at presentation; and 12.6 (95%CI 2.2-72.0) for severely impaired mental status at presentation. Factors associated with a door-to-antibiotic time of >6 h were: (i) failure to administer antibiotics prior to transfer from another institution (OR 21.8); (ii) the diagnostic-treatment sequence: head CT then lumbar puncture, then antibiotics (OR 5.6); and (iii) the absence of the classic meningitis triad (OR 4.9).
DISCUSSION: There is an independent incremental association between delays in administrating antibiotics and mortality from adult acute bacterial meningitis. Inappropriate diagnostic-treatment sequences were significant predictors of such treatment delays.
Desmond RA, Accortt NA, Talley L, Villano SA, Soong SJ, Whitley RJ.
Enteroviral meningitis: natural history and outcome of pleconaril therapy.
Antimicrob Agents Chemother. 2006 Jul;50(7):2409-14. doi: 10.1128/AAC.00227-06.
Abstract/Text
Enteroviral meningitis causes appreciable morbidity in adults, including hospitalization, decreased activity, and headache. Limited data define the natural history of disease. No antiviral therapeutic agent has demonstrated improved outcome in controlled clinical trials. Pleconaril, an inhibitor of enterovirus replication, was tested in two placebo-controlled clinical trials. Of 607 randomized patients in a multicenter, double-blind placebo-controlled study of pleconaril (200 mg three times daily versus an identical-appearing placebo), 240 patients were confirmed to have enterovirus infection. The time to headache resolution was evaluated by using Kaplan-Meier survival methodology. A Cox regression model evaluated multivariate factors associated with disease resolution. Resolution of headache in patients with concomitant moderate to severe nausea at baseline occurred at a median of 9.5 days in the absence of therapy and was reduced to 7.0 days for pleconaril recipients (P = 0.009). For a headache score of > 5 alone, treated patients resolved headache significantly more rapidly (P = 0.005). Males resolved headache 50% faster than females. Regardless of randomization group, patients with a baseline headache score of 5 or greater resolved headache 50% more slowly than patients with a baseline headache score of 4. No differences in either clinical or laboratory adverse events were noted. Over 50% of untreated patients had a persistent headache that was greater than 1 week in duration. Pleconaril shortened the course of illness compared to placebo recipients, especially in the early disease course. However, the benefit was achieved only modestly in a subgroup analysis of patients with more severe disease after adjusting for confounding variables.
Whitley RJ, Alford CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY, Hanley D, Nahmias AJ, Soong SJ.
Vidarabine versus acyclovir therapy in herpes simplex encephalitis.
N Engl J Med. 1986 Jan 16;314(3):144-9. doi: 10.1056/NEJM198601163140303.
Abstract/Text
We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.
Sköldenberg B, Forsgren M, Alestig K, Bergström T, Burman L, Dahlqvist E, Forkman A, Frydén A, Lövgren K, Norlin K.
Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients.
Lancet. 1984 Sep 29;2(8405):707-11. doi: 10.1016/s0140-6736(84)92623-0.
Abstract/Text
127 patients with suspected herpes simplex encephalitis (HSE) were entered in a prospective randomised study of acyclovir 10 mg/kg 8-hourly versus vidarabine 15 mg/kg daily for 10 days. The patients were consecutive and nearly all Swedish cases of HSE were included; they were treated in six university infectious diseases departments. The diagnosis of HSE was verified by brain biopsy and/or antibody responses in serum and cerebrospinal fluid. Of 53 confirmed cases of HSE (corresponding to 2 X 3 cases per million inhabitants per year in Sweden), 51 (27 acyclovir, 24 vidarabine) were evaluable for analysis of efficacy. The mortality was 19% in the acyclovir-treated group versus 50% in the vidarabine group (p = 0.04). At 6 months of observation 15 (56%) of 27 acyclovir-treated patients had returned to normal life compared with 3 (13%) of 24 vidarabine-treated patients (p = 0.002); and the numbers who died or had severe sequelae were 9 (33%) and 19 (76%), respectively (p = 0.005). No important or new adverse events were recognised.
