今日の臨床サポート

無菌性髄膜炎

著者: 笠原 敬 奈良県立医科大学 感染症センター

監修: 大曲貴夫 国立国際医療研究センター

著者校正/監修レビュー済:2021/06/30
参考ガイドライン:
  1. 日本神経学会日本神経治療学会日本神経感染症学会:細菌性髄膜炎診療ガイドライン2014
患者向け説明資料

概要・推奨   

  1. 無菌性髄膜炎に標準的・統一的な定義はない。広義には肺炎球菌やインフルエンザ菌などの細菌性髄膜炎の原因となる細菌が認められない髄膜炎全般を指すが、狭義にはエンテロウイルス属やムンプスウイルス、HSVやVZVなどによるウイルス性髄膜炎を指すこともある。
  1. 発熱、頭痛、嘔気・嘔吐、羞明といった症状や、項部硬直、Kernig徴候、Brudzinski徴候、Jolt accentuationなどの身体所見から総合的に髄膜炎の有無を判断する。
  1. 病歴や身体所見から髄膜炎の原因を鑑別することは困難であり、特に細菌性髄膜炎が否定できない場合は、髄液検査を行う(推奨度1)。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
笠原 敬 : 研究費・助成金など(奈良県立医科大学:新型コロナウイルス感染症対策強化に資する基礎研究),奨学(奨励)寄付など(塩野義製薬株式会社,大鵬薬品工業株式会社,塩野義製薬株式会社)[2021年]
監修:大曲貴夫 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、無菌性髄膜炎により特化した本文構成とした。また5類感染症として定点医療期間で届出を行う場合、状況によっては地方衛生研究所で髄液、便、咽頭拭い液などを用いたウイルス検査が行われることを追記した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 無菌性髄膜炎に標準的・統一的な定義はない。
  1. 無菌性髄膜炎は広義には肺炎球菌やインフルエンザ菌などの細菌性髄膜炎の原因となる細菌が認められない髄膜炎全般を指すが(表)、一般的にはウイルス性髄膜炎、特に後述するエンテロウイルス属による髄膜炎を指すことが多い。
 
無菌性髄膜炎に含まれる疾患群(鑑別疾患)

出典

img1:  著者提供
 
 
 
  1. 無菌性髄膜炎は5類感染症(基幹定点医療機関)に指定されており、毎年1,000例前後が報告されている。年齢分布では小児例(10歳未満)が40%と多いが、20歳以上も約50%を占め、全ての年齢にみられる[1]
  1. 無菌性髄膜炎患者から検出されるウイルスとしては、エンテロウイルス(6, 30, A71など)、コクサッキーウイルス(B5など)などのエンテロウイルス属が50~80%を占め、その他にムンプスウイルスやパレコウイルス(3)などが検出されている。
  1. エンテロウイルス属による無菌性髄膜炎は特に夏に多い。またエンテロウイルス(特に30)は地域的な流行による患者数の増加がしばしば報告されている[1]
病歴・診察のポイント  
  1. 発熱、頭痛、嘔気・嘔吐、羞明といった症状や、項部硬直、Kernig徴候、Brudzinski徴候、Jolt accentuationなどの身体所見から総合的に髄膜炎の有無を判断する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: A Viallon, F Zeni, C Lambert, B Pozzetto, B Tardy, C Venet, J C Bertrand
雑誌名: 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.

PMID 10451174  Clin Infect Dis. 1999 Jun;28(6):1313-6. doi: 10.1086/51・・・
著者: François Dubos, Bartosz Korczowski, Denizmen A Aygun, Alain Martinot, Cristina Prat, Annick Galetto-Lacour, Juan Casado-Flores, Erdal Taskin, Francis Leclerc, Carlos Rodrigo, Alain Gervaix, Sandrine Leroy, Dominique Gendrel, Gérard Bréart, Martin Chalumeau
雑誌名: 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.

PMID 19047543  Arch Pediatr Adolesc Med. 2008 Dec;162(12):1157-63. doi・・・
著者: Francois Dubos, Florence Moulin, Vincent Gajdos, Nathalie De Suremain, Sandra Biscardi, Pierre Lebon, Josette Raymond, Gerard Breart, Dominique Gendrel, Martin Chalumeau
雑誌名: 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.

PMID 16860131  J Pediatr. 2006 Jul;149(1):72-6. doi: 10.1016/j.jpeds.2・・・
著者: D C Tanner, M P Weinstein, B Fedorciw, K L Joho, J J Thorpe, L Reller
雑誌名: J Clin Microbiol. 1994 Jul;32(7):1680-4.
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.

PMID 7929757  J Clin Microbiol. 1994 Jul;32(7):1680-4.
著者: Brajagopal Ray, George Rylance
雑誌名: Arch Dis Child. 2009 Dec;94(12):988-91. doi: 10.1136/adc.2009.163766.
Abstract/Text
PMID 19933606  Arch Dis Child. 2009 Dec;94(12):988-91. doi: 10.1136/ad・・・
著者: Ken Sakushima, Yasuaki Hayashino, Takehiko Kawaguchi, Jeffrey L Jackson, Shunichi Fukuhara
雑誌名: 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.
PMID 21382412  J Infect. 2011 Apr;62(4):255-62. doi: 10.1016/j.jinf.20・・・
著者: S I Aronin, P Peduzzi, V J Quagliarello
雑誌名: Ann Intern Med. 1998 Dec 1;129(11):862-9.
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.

PMID 9867727  Ann Intern Med. 1998 Dec 1;129(11):862-9.
著者: Marc Auburtin, Michel Wolff, Julien Charpentier, Emmanuelle Varon, Yves Le Tulzo, Christophe Girault, Ismaël Mohammedi, Benoît Renard, Bruno Mourvillier, Fabrice Bruneel, Jean-Damien Ricard, Jean-François Timsit
雑誌名: 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.

PMID 16915106  Crit Care Med. 2006 Nov;34(11):2758-65. doi: 10.1097/01・・・
著者: D Lepur, B Barsić
雑誌名: 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.

PMID 17646915  Infection. 2007 Jun;35(4):225-31. doi: 10.1007/s15010-0・・・
著者: N Proulx, D Fréchette, B Toye, J Chan, S Kravcik
雑誌名: 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.

PMID 15760921  QJM. 2005 Apr;98(4):291-8. doi: 10.1093/qjmed/hci047. E・・・
著者: R A Desmond, N A Accortt, L Talley, S A Villano, S-J Soong, R J Whitley
雑誌名: 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.

PMID 16801419  Antimicrob Agents Chemother. 2006 Jul;50(7):2409-14. do・・・
著者: R J Whitley, C A Alford, M S Hirsch, R T Schooley, J P Luby, F Y Aoki, D Hanley, A J Nahmias, S J Soong
雑誌名: 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.

PMID 3001520  N Engl J Med. 1986 Jan 16;314(3):144-9. doi: 10.1056/NE・・・
著者: B Sköldenberg, M Forsgren, K Alestig, T Bergström, L Burman, E Dahlqvist, A Forkman, A Frydén, K Lövgren, K Norlin
雑誌名: Lancet. 1984 Sep 29;2(8405):707-11.
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.

PMID 6148470  Lancet. 1984 Sep 29;2(8405):707-11.

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