今日の臨床サポート

細菌性髄膜炎

概要・推奨   

  1. jolt accentuationが陰性の場合、髄膜炎を除外することはおそらく推奨されない(推奨度3、S
  1. 細菌性髄膜炎において古典的3徴(発熱、項部硬直、意識障害)が揃わなくとも、細菌性髄膜炎を除外しないことが推奨される(推奨度2、G、S
  1. 抗菌薬を開始する前に2セット以上の血液培養を採取することは強く推奨される(推奨度1、J、G
  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。
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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。
  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
  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
  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
  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。閲覧にはご契約が必要となります。閲
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:
山元佳 : 研究費・助成金など(富士レビオ株式会社,株式会社ミズホメディー,株式会社ビズジーン)[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:

病態・疫学・診察

疾患情報  
  1. 細菌性髄膜炎とは、クモ膜下腔の髄液内に細菌が侵入して炎症を引き起こす疾患である。
  1. 内科緊急疾患であり、迅速な治療開始が必要である。
  1. 肺炎球菌、インフルエンザ桿菌、髄膜炎菌が原因の約75~80%を占め、3カ月未満ではB群レンサ球菌、3カ月以上の小児・成人では肺炎球菌が最も多い。日本国内では髄膜炎菌が欧米と比べて少ないことが特徴である。
  1. 小児に対するインフルエンザ桿菌b(Hib)ワクチンと肺炎球菌結合型ワクチン(PCV)の導入により日本でもHibによる髄膜炎は激減し、肺炎球菌も減少に転じている。
  1. 細菌性髄膜炎とウイルス性髄膜炎を臨床的に区別することはしばしば困難である。
問診・診察のポイント  
問診:
  1. 頭痛の強さ、随伴症状を確認する(急激な強い頭痛が典型的である)。

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

詳しくはクリック
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Hidetaka Tamune, Takaie Kuki, Tetsuya Kashiyama, Toshiki Uchihara
雑誌名: Headache. 2018 Nov;58(10):1503-1510. doi: 10.1111/head.13376. Epub 2018 Sep 4.
Abstract/Text OBJECTIVE: In order to identify appropriate candidates with suspected meningitis for lumbar puncture (LP), study designs and diagnostic values of jolt accentuation of headache (JA) were reviewed.
BACKGROUND: Acute meningitis is a life-threatening disease that requires LP for accurate diagnosis. JA was reported the most sensitive indicator of cerebrospinal fluid pleocytosis; however, subsequent studies have failed to confirm this claim.
METHODS: We reviewed articles concerning JA, published prior to December 2017, using MEDLINE and Japanese medical databases. Seven original articles based on independent cohorts were eligible for inclusion and articles citing these 7 were thoroughly searched (11 in total). Additionally, all medical records of our previously reported cohort were reviewed again to explore how the patients' background influenced diagnostic values of JA.
RESULTS: We hypothesized that an oversimplified dichotomy of JA findings, pleocytosis, and meningitis created a misconception that JA is a universal indicator of meningitis. We clarify the difference between them and present altered mental status (AMS) as a key to decrease the sensitivity of JA. Notably, the sensitivity and specificity of JA were relatively low in unselected groups, while they tended to be high in the selected sub-groups with acute onset of headache and fever, without AMS or neurological deficits. Unselected populations included etiologies of pleocytosis other than acute meningitis, which might weaken the association between JA and pleocytosis.
CONCLUSION: JA is not a universal, stand-alone, indicator of meningitis in febrile patients with headache. Therefore, we propose a stepwise approach for patients with suspected acute meningitis. AMS or neurological deficits suggest an intracranial pathology, which may necessitate a lumbar puncture. JA seems a useful tool for distinguishing acute aseptic meningitis from upper respiratory infection when used in the selected cohort of febrile patients (≥37°C) with recent-onset headache (within 2 weeks before presentation) and normal mental status. This approach and diagnostic values of JA should be further investigated by prospective studies using operationally sorted candidates.

© 2018 American Headache Society.
PMID 30178879  Headache. 2018 Nov;58(10):1503-1510. doi: 10.1111/head.・・・
著者: T Uchihara, H Tsukagoshi
雑誌名: Headache. 1991 Mar;31(3):167-71.
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.

PMID 2071396  Headache. 1991 Mar;31(3):167-71.
著者: Karen E Thomas, Rodrigo Hasbun, James Jekel, Vincent J Quagliarello
雑誌名: Clin Infect Dis. 2002 Jul 1;35(1):46-52. doi: 10.1086/340979. Epub 2002 Jun 5.
Abstract/Text To determine the diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity for meningitis, 297 adults with suspected meningitis were prospectively evaluated for the presence of these meningeal signs before lumbar puncture was done. Kernig's sign (sensitivity, 5%; likelihood ratio for a positive test result [LR(+)], 0.97), Brudzinski's sign (sensitivity, 5%; LR(+), 0.97), and nuchal rigidity (sensitivity, 30%; LR(+), 0.94) did not accurately discriminate between patients with meningitis (>/=6 white blood cells [WBCs]/mL of cerebrospinal fluid [CSF]) and patients without meningitis. The diagnostic accuracy of these signs was not significantly better in the subsets of patients with moderate meningeal inflammation (>/=100 WBCs/mL of CSF) or microbiological evidence of CSF infection. Only for 4 patients with severe meningeal inflammation (>/=1000 WBCs/mL of CSF) did nuchal rigidity show diagnostic value (sensitivity, 100%; negative predictive value, 100%). In the broad spectrum of adults with suspected meningitis, 3 classic meningeal signs did not have diagnostic value; better bedside diagnostic signs are needed.

PMID 12060874  Clin Infect Dis. 2002 Jul 1;35(1):46-52. doi: 10.1086/3・・・
著者: Diederik van de Beek, Jan de Gans, Lodewijk Spanjaard, Martijn Weisfelt, Johannes B Reitsma, Marinus Vermeulen
雑誌名: N Engl J Med. 2004 Oct 28;351(18):1849-59. doi: 10.1056/NEJMoa040845.
Abstract/Text BACKGROUND: We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis.
METHODS: From October 1998 to April 2002, all Dutch patients with community-acquired acute bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively evaluated. All patients underwent a neurologic examination on admission and at discharge, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discharge) or favorable (a score of 5). Predictors of an unfavorable outcome were identified through logistic-regression analysis.
RESULTS: We evaluated 696 episodes of community-acquired acute bacterial meningitis. The most common pathogens were Streptococcus pneumoniae (51 percent of episodes) and Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness, and a change in mental status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. On admission, 14 percent of patients were comatose and 33 percent had focal neurologic abnormalities. The overall mortality rate was 21 percent. The mortality rate was higher among patients with pneumococcal meningitis than among those with meningococcal meningitis (30 percent vs. 7 percent, P<0.001). The outcome was unfavorable in 34 percent of episodes. Risk factors for an unfavorable outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission, tachycardia, a positive blood culture, an elevated erythrocyte sedimentation rate, thrombocytopenia, and a low cerebrospinal fluid white-cell count.
CONCLUSIONS: In adults presenting with community-acquired acute bacterial meningitis, the sensitivity of the classic triad of fever, neck stiffness, and altered mental status is low, but almost all present with at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. The mortality associated with bacterial meningitis remains high, and the strongest risk factors for an unfavorable outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S. pneumoniae.

Copyright 2004 Massachusetts Medical Society.
PMID 15509818  N Engl J Med. 2004 Oct 28;351(18):1849-59. doi: 10.1056・・・
著者: Jan de Gans, Diederik van de Beek, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators
雑誌名: N Engl J Med. 2002 Nov 14;347(20):1549-56. doi: 10.1056/NEJMoa021334.
Abstract/Text BACKGROUND: Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.
METHODS: We conducted a prospective, randomized, double-blind, multicenter trial of adjuvant treatment with dexamethasone, as compared with placebo, in adults with acute bacterial meningitis. Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the first dose of antibiotic and was given every 6 hours for four days. The primary outcome measure was the score on the Glasgow Outcome Scale at eight weeks (a score of 5, indicating a favorable outcome, vs. a score of 1 to 4, indicating an unfavorable outcome). A subgroup analysis according to the causative organism was performed. Analyses were performed on an intention-to-treat basis.
RESULTS: A total of 301 patients were randomly assigned to a treatment group: 157 to the dexamethasone group and 144 to the placebo group. The base-line characteristics of the two groups were similar. Treatment with dexamethasone was associated with a reduction in the risk of an unfavorable outcome (relative risk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03). Treatment with dexamethasone was also associated with a reduction in mortality (relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04). Among the patients with pneumococcal meningitis, there were unfavorable outcomes in 26 percent of the dexamethasone group, as compared with 52 percent of the placebo group (relative risk, 0.50; 95 percent confidence interval, 0.30 to 0.83; P=0.006). Gastrointestinal bleeding occurred in two patients in the dexamethasone group and in five patients in the placebo group.
CONCLUSIONS: Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding.

Copyright 2002 Massachusetts Medical Society
PMID 12432041  N Engl J Med. 2002 Nov 14;347(20):1549-56. doi: 10.1056・・・
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: T T Thanh, C Casals-Pascual, N T H Ny, N M Ngoc, R Geskus, L N T Nhu, N T T Hong, D T Duc, D D A Thu, P N Uyen, V B Ngoc, L T M Chau, V X Quynh, N H H Hanh, N T T Thuong, L T Diem, B T B Hanh, V T T Hang, P K N Oanh, R Fischer, N H Phu, H D T Nghia, N V V Chau, N T Hoa, B M Kessler, G Thwaites, L V Tan
雑誌名: Clin Microbiol Infect. 2020 Jul 11;. doi: 10.1016/j.cmi.2020.07.006. Epub 2020 Jul 11.
Abstract/Text OBJECTIVES: Central nervous system (CNS) infections are common causes of morbidity and mortality worldwide. We aimed to discover protein biomarkers that could rapidly and accurately identify the likely cause of the infections, essential for clinical management and improving outcome.
METHODS: We applied liquid chromatography tandem mass spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with and without CNS infections to discover potential diagnostic biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in Vietnam.
RESULTS: In the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis (BM) other than tuberculous meningitis. The analysis of the validation cohort showed that LCN2 could discriminate BM from other CNS infections (including tuberculous meningitis, cryptococcal meningitis and virus/antibody-mediated encephalitis), with sensitivity of 0.88 (95% confident interval (CI), 0.77-0.94), specificity of 0.91 (95% CI, 0.88-0.94) and diagnostic odds ratio of 73.8 (95% CI, 31.8-171.4). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2, CSF leukocytes, glucose, protein and lactate resulted in the highest diagnostic performance for BM (area under the receiver operating characteristics curve, 0.96; 95% CI, 0.93-0.99). Data are available via ProteomeXchange with identifier PXD020510.
CONCLUSIONS: LCN2 is a sensitive and specific biomarker for discriminating BM from a broad spectrum of other CNS infections. A prospective study is needed to assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections.

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
PMID 32659386  Clin Microbiol Infect. 2020 Jul 11;. doi: 10.1016/j.cmi・・・
著者: Tomohiro Taniguchi, Sanefumi Tsuha, Soichi Shiiki, Masashi Narita
雑誌名: Ann Clin Microbiol Antimicrob. 2020 Dec 7;19(1):59. doi: 10.1186/s12941-020-00404-9. Epub 2020 Dec 7.
Abstract/Text BACKGROUND: Gram stain of cerebrospinal fluid (CSF) is widely used in the diagnosis of acute meningitis, however, it is often conducted in the laboratory, as only some hospitals have access to point-of-care Gram stain (PCGS). The purpose of this study was to demonstrate the clinical impact and utility of PCGS in diagnosing and treating both bacterial and aseptic meningitis in adults.
METHODS: This was a hospital-based, retrospective observational study at a referral center in Okinawa, Japan. We reviewed the records of all patients aged 15 years or older who were admitted to the Division of Infectious Diseases between 1995 and 2015 and finally diagnosed with bacterial (n = 34) or aseptic meningitis (n = 97). For bacterial meningitis, we compared the treatments that were actually selected based on PCGS with simulated treatments that would have been based on the Japanese guidelines. For aseptic meningitis, we compared the rates of antibiotic use between real cases where PCGS was available and real cases where it was not.
RESULTS: PCGS was the most precise predictor for differentiating between bacterial and aseptic meningitis (sensitivity 91.2%, specificity 98.9%), being superior in this regard to medical histories, vital signs and physical examinations, and laboratory data available in the emergency room (ER). In bacterial meningitis, PCGS reduced the frequency of meropenem use (1/34 = 3.0%) compared with simulated cases in which PCGS was not available (19/34 = 55.9%) (p< 0.001). In aseptic meningitis cases, the rate of antibiotic administration was lower when PCGS was used (38/97 = 39.2%) than when it was not (45/74 = 60.8%) (p = 0.006).
CONCLUSIONS: PCGS of CSF distinguishes between bacterial and aseptic meningitis more accurately than other predictors available in the ER. Patients with bacterial meningitis are more likely to receive narrower-spectrum antimicrobials when PCGS is used than when it is not. PCGS of CSF thus can potentially suppress the empiric use of antimicrobials for aseptic meningitis.

PMID 33287843  Ann Clin Microbiol Antimicrob. 2020 Dec 7;19(1):59. doi・・・
著者: Allan R Tunkel, Barry J Hartman, Sheldon L Kaplan, Bruce A Kaufman, Karen L Roos, W Michael Scheld, Richard J Whitley
雑誌名: Clin Infect Dis. 2004 Nov 1;39(9):1267-84. doi: 10.1086/425368. Epub 2004 Oct 6.
Abstract/Text
PMID 15494903  Clin Infect Dis. 2004 Nov 1;39(9):1267-84. doi: 10.1086・・・
著者: D T Durack, A Spanos
雑誌名: JAMA. 1982 Jul 2;248(1):75-8.
Abstract/Text
PMID 7087096  JAMA. 1982 Jul 2;248(1):75-8.
著者: Lisanne Denneman, Amandine Vial-Dupuy, Nathalie Gault, Michel Wolff, Diederik van de Beek, Bruno Mourvillier
雑誌名: J Infect. 2013 Oct;67(4):350-3. doi: 10.1016/j.jinf.2013.05.001. Epub 2013 May 9.
Abstract/Text
PMID 23664854  J Infect. 2013 Oct;67(4):350-3. doi: 10.1016/j.jinf.201・・・
著者: Joseph Y Ting, Ashley Roberts, Sarah Khan, Ari Bitnun, Michael Hawkes, Michelle Barton, Jennifer Bowes, Jason Brophy, Lynda Ouchenir, Christian Renaud, Andrée-Anne Boisvert, Jane McDonald, Joan L Robinson
雑誌名: PLoS One. 2020;15(8):e0238056. doi: 10.1371/journal.pone.0238056. Epub 2020 Aug 28.
Abstract/Text BACKGROUND: There are variations in recommendations from different guidelines regarding the indications for repeat lumbar puncture (LP) in young infants with the diagnosis of bacterial meningitis.
OBJECTIVE: To evaluate the frequency of repeat LPs and the characteristics of cerebrospinal fluid (CSF) parameters in repeated sampling and their predictive values for adverse outcomes in a national cohort.
METHODS: This cohort study included infants born January 1, 2013 through December 31, 2014, who had proven or suspected bacterial meningitis within the first 90 days of life at seven paediatric tertiary care hospitals across Canada, and who underwent a repeat LP at the discretion of the treating physicians.
RESULTS: Forty-nine of 111 infants (44%) underwent repeat LP at a median of 5 (IQR: 3, 13) days after the LP that led to the diagnosis of bacterial meningitis. Those who had meningitis caused by gram negative bacilli were more likely to have repeat LP than those with gram positive bacteria (77% versus 57%; p = 0.012). White blood cell (WBC) count on the second spinal tap yielded an area under the curve of 0.88 for predicting sequelae of meningitis at discharge from the hospital, with a cut-off value of 366 × 106/L, providing a sensitivity of 91% and specificity of 88%.
CONCLUSION: In this multi-centre retrospective cohort study, infants with gram negative meningitis were more likely to have repeated LP. A high WBC on the second CSF sample was predictive of adverse outcome at the time of discharge from the hospital.

PMID 32857801  PLoS One. 2020;15(8):e0238056. doi: 10.1371/journal.pon・・・
著者: Matthijs C Brouwer, Allan R Tunkel, Diederik van de Beek
雑誌名: Clin Microbiol Rev. 2010 Jul;23(3):467-92. doi: 10.1128/CMR.00070-09.
Abstract/Text The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women. Given the significant morbidity and mortality associated with bacterial meningitis, accurate information is necessary regarding the important etiological agents and populations at risk to ascertain public health measures and ensure appropriate management. In this review, we describe the changing epidemiology of bacterial meningitis in the United States and throughout the world by reviewing the global changes in etiological agents followed by specific microorganism data on the impact of the development and widespread use of conjugate vaccines. We provide recommendations for empirical antimicrobial and adjunctive treatments for clinical subgroups and review available laboratory methods in making the etiological diagnosis of bacterial meningitis. Finally, we summarize risk factors, clinical features, and microbiological diagnostics for the specific bacteria causing this disease.

PMID 20610819  Clin Microbiol Rev. 2010 Jul;23(3):467-92. doi: 10.1128・・・
著者: Isabelle Parent du Châtelet, Yves Traore, Bradford D Gessner, Aude Antignac, B Naccro, Berthe-Marie Njanpop-Lafourcade, Macaire S Ouedraogo, Sylvestre R Tiendrebeogo, Emmanuelle Varon, Muhammed K Taha
雑誌名: Clin Infect Dis. 2005 Jan 1;40(1):17-25. doi: 10.1086/426436. Epub 2004 Dec 8.
Abstract/Text BACKGROUND: In addition to frequent epidemics of group A meningococcal disease, endemic bacterial meningitis due mostly to Neisseria meningitidis, pneumococcus, and Haemophilus influenzae type b is a serious problem in sub-Saharan Africa. The improved ability to identify the etiologic agent in cases of bacterial meningitis will facilitate more rapid administration of precise therapy.
METHODS: To describe the epidemiology of bacterial meningitis and evaluate the usefulness of field-based polymerase chain reaction (PCR) testing, we implemented population-based meningitis surveillance in Burkina Faso during 2002-2003 by use of PCR, culture, and antigen detection tests.
RESULTS: Among persons aged 1 month to 67 years, the incidences of meningococcal meningitis, pneumococcal meningitis, and Haemophilus influenzae type b meningitis were 19 cases (n=179), 17 cases (n=162), and 7.1 cases (n=68) per 100,000 persons per year, respectively. Of the cases of meningococcal meningitis, 72% were due to N. meningitidis serogroup W135. Pneumococcal meningitis caused 61% of deaths and occurred in a seasonal pattern that was similar to that of meningococcal meningitis. Of cases of pneumococcal meningitis and N. meningitidis serogroup W135 meningitis, 71% occurred among persons >2 years of age. Most patients, regardless of the etiology of their illness and the existence of an epidemic, received short-course therapy with oily chloramphenicol. Compared with culture as the gold standard, the sensitivity and specificity of PCR in the field were high; this result was confirmed in Burkina Faso and Paris.
CONCLUSIONS: Precise and rapid identification of etiologic agents is critical for improvement in the treatment and prevention of meningitis, and, thus, PCR should be considered for wider use in Africa. Vaccines against Streptococcus pneumoniae, N. meningitidis (including serogroup W135), and H. influenzae type b all will have a major impact on the bacterial meningitis burden. Antibiotic recommendations need to consider the importance of S. pneumoniae, even during the epidemic season.

PMID 15614687  Clin Infect Dis. 2005 Jan 1;40(1):17-25. doi: 10.1086/4・・・
著者: Carmen Munoz-Almagro, Maria T Rodriguez-Plata, Silvia Marin, Cristina Esteva, Elisabeth Esteban, Amadeu Gene, Gemma Gelabert, Iolanda Jordan
雑誌名: Diagn Microbiol Infect Dis. 2009 Feb;63(2):148-54. doi: 10.1016/j.diagmicrobio.2008.10.008. Epub 2008 Nov 21.
Abstract/Text A prospective study was performed including all children younger than 18 years with the clinical diagnosis of invasive meningococcal disease (IMD) hospitalized at the University Hospital Sant Joan de Déu in Barcelona, Spain, from January 2001 to December 2006. During the study period, 168 meningococcal disease cases were reported. Microbiologic confirmation was obtained in 118 cases. Forty-six (38.9%) of 118 cases were only detected by polymerase chain reaction (PCR); 6 patients were culture positive and PCR negative (5%). Serogroup B predominated in the 6-year period with 83.1% of the strains. A significant decrease in serogroup C was observed in the last 3 years of the study (P=0.029), and less common serogroups, such as serogroup A and W135, emerged. Serogroup distribution of patient diagnoses only by real-time PCR showed a similar distribution: serogroup B, 85.7%; serogroup C, 7.1%; and nontypeable serogroups, 7.1%. In conclusion, real-time PCR is more rapid and sensitive than culture for diagnosis and serogrouping of IMD.

PMID 19026504  Diagn Microbiol Infect Dis. 2009 Feb;63(2):148-54. doi:・・・
著者: Lise E Nigrovic, Richard Malley, Charles G Macias, John T Kanegaye, Donna M Moro-Sutherland, Robert D Schremmer, Sandra H Schwab, Dewesh Agrawal, Karim M Mansour, Jonathan E Bennett, Yiannis L Katsogridakis, Michael M Mohseni, Blake Bulloch, Dale W Steele, Ron L Kaplan, Martin I Herman, Subhankar Bandyopadhyay, Peter Dayan, Uyen T Truong, Vince J Wang, Bema K Bonsu, Jennifer L Chapman, Nathan Kuppermann, American Academy of Pediatrics, Pediatric Emergency Medicine Collaborative Research Committee
雑誌名: Pediatrics. 2008 Oct;122(4):726-30. doi: 10.1542/peds.2007-3275.
Abstract/Text OBJECTIVE: The goal of this study was to evaluate the effect of antibiotic administration before lumbar puncture on cerebrospinal fluid profiles in children with bacterial meningitis.
METHODS: We reviewed the medical records of all children (1 month to 18 years of age) with bacterial meningitis who presented to 20 pediatric emergency departments between 2001 and 2004. Bacterial meningitis was defined by positive cerebrospinal fluid culture results for a bacterial pathogen or cerebrospinal fluid pleocytosis with positive blood culture and/or cerebrospinal fluid latex agglutination results. Probable bacterial meningitis was defined as positive cerebrospinal fluid Gram stain results with negative results of bacterial cultures of blood and cerebrospinal fluid. Antibiotic pretreatment was defined as any antibiotic administered within 72 hours before the lumbar puncture.
RESULTS: We identified 231 patients with bacterial meningitis and another 14 with probable bacterial meningitis. Of those 245 patients, 85 (35%) had received antibiotic pretreatment. After adjustment for patient age, duration and severity of illness at presentation, and bacterial pathogen, longer duration of antibiotic pretreatment was not significantly associated with cerebrospinal fluid white blood cell count, cerebrospinal fluid absolute neutrophil count. However, antibiotic pretreatment was significantly associated with higher cerebrospinal fluid glucose and lower cerebrospinal fluid protein levels. Although these effects became apparent earlier, patients with >or=12 hours of pretreatment, compared with patients who either were not pretreated or were pretreated for <12 hours, had significantly higher median cerebrospinal fluid glucose levels (48 mg/dL vs 29 mg/dL) and lower median cerebrospinal fluid protein levels (121 vs 178 mg/dL).
CONCLUSIONS: In patients with bacterial meningitis, antibiotic pretreatment is associated with higher cerebrospinal fluid glucose levels and lower cerebrospinal fluid protein levels, although pretreatment does not modify cerebrospinal fluid white blood cell count or absolute neutrophil count results.

PMID 18829794  Pediatrics. 2008 Oct;122(4):726-30. doi: 10.1542/peds.2・・・
著者: R Hasbun, J Abrahams, J Jekel, V J Quagliarello
雑誌名: N Engl J Med. 2001 Dec 13;345(24):1727-33. doi: 10.1056/NEJMoa010399.
Abstract/Text BACKGROUND: In adults with suspected meningitis clinicians routinely order computed tomography (CT) of the head before performing a lumbar puncture.
METHODS: We prospectively studied 301 adults with suspected meningitis to determine whether clinical characteristics that were present before CT of the head was performed could be used to identify patients who were unlikely to have abnormalities on CT. The Modified National Institutes of Health Stroke Scale was used to identify neurologic abnormalities.
RESULTS: Of the 301 patients with suspected meningitis, 235 (78 percent) underwent CT of the head before undergoing lumbar puncture. In 56 of the 235 patients (24 percent), the results of CT were abnormal; 11 patients (5 percent) had evidence of a mass effect. The clinical features at base line that were associated with an abnormal finding on CT of the head were an age of at least 60 years, immunocompromise, a history of central nervous system disease, and a history of seizure within one week before presentation, as well as the following neurologic abnormalities: an abnormal level of consciousness, an inability to answer two consecutive questions correctly or to follow two consecutive commands, gaze palsy, abnormal visual fields, facial palsy, arm drift, leg drift, and abnormal language (e.g., aphasia). None of these features were present at base line in 96 of the 235 patients who underwent CT scanning of the head (41 percent). The CT scan was normal in 93 of these 96 patients, yielding a negative predictive value of 97 percent. Of the three misclassified patients, only one had a mild mass effect on CT, and all three subsequently underwent lumbar puncture, with no evidence of brain herniation one week later.
CONCLUSIONS: In adults with suspected meningitis, clinical features can be used to identify those who are unlikely to have abnormal findings on CT of the head.

PMID 11742046  N Engl J Med. 2001 Dec 13;345(24):1727-33. doi: 10.1056・・・
著者: Masayoshi Shinjoh, Yoshio Yamaguchi, Satoshi Iwata
雑誌名: J Infect Chemother. 2017 Jul;23(7):427-438. doi: 10.1016/j.jiac.2017.02.014. Epub 2017 Apr 26.
Abstract/Text BACKGROUND: Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugated vaccine (PCV) have been widely used since 2010 in Japan when both vaccines were supported by the regional governments, and they were covered as routine recommended vaccines in 2013. The incidence of bacterial meningitis due to these organisms decreased in 2011 and 2012, but meningitis due to Streptococcus agalactiae and Escherichia coli remained unchanged.
OBJECTIVES: We planned to confirm whether the incidence also decreased in subsequent years.
METHODS: We analyzed the epidemiological and clinical data for 2013-2015, and compared the information obtained in the previous nationwide survey database and our previous reports. We also investigated the risk factors for disease outcome.
RESULTS: In the 2013-2015 surveys, 407 patients from 366 hospitals from all prefectures were evaluated. S. agalactiae (33%), Streptococcus pneumoniae (25%), and E. coli (10%) were the main organisms. The total number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.19 in 2009-2010 to 0.37 in 2013-2015 (p < 0.001). The incidence of H. influenzae and S. pneumoniae meningitis significantly decreased from 0.66 in 2009-2010 to 0.01 in 2013-2015, and from 0.30 to 0.09, respectively (p < 0.001). Only 0-2 cases with Neisseria meningitidis were reported each year throughout 2001-2015. The fatality rates for H. influenzae, S. pneumoniae, S. agalactiae, and E. coli in 2013-2015 were 0.0, 4.1, 3.1, and 2.6%, respectively. Risk factors for death and sequelae were consciousness disturbance, convulsion, low CSF glucose, and Staphylococcus sp. as a causative organism (p < 0.01).
CONCLUSIONS: Hib vaccine and PCV have decreased the rate of bacterial meningitis. S. agalactiae has subsequently become the most common cause of bacterial meningitis in Japan.

Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 28456490  J Infect Chemother. 2017 Jul;23(7):427-438. doi: 10.101・・・
著者: J M Bell, J D Turnidge, R N Jones, SENTRY Regional Participants Group
雑誌名: Int J Antimicrob Agents. 2002 Feb;19(2):125-32.
Abstract/Text From 1998 to 1999, a large number of community-acquired respiratory tract isolates of Streptococcus pneumoniae (n=566), Haemophilus influenzae (n=513) and Moraxella catarrhalis (n=228) were collected from 15 centres in Australia, Hong Kong, Japan, China, the Philippines, Singapore, South Africa and Taiwan through the SENTRY Antimicrobial Surveillance Program. Isolates were tested against 26 antimicrobial agents using the NCCLS-recommended methods. Overall, 40% of S. pneumoniae isolates were resistant to penicillin with 18% of strains having high-level resistance (MIC > or =2 mg/l). Rates of erythromycin and clindamycin resistance were 41 and 23%, respectively. Penicillin-resistant strains showed high rates of resistance to other antimicrobial agents: 96% to trimethoprim-sulphamethoxazole (TMP-SMX), 84% to tetracycline and 81% to erythromycin. A significant proportion of penicillin-susceptible strains was also resistant to erythromycin (21%), tetracycline (29%) and TMP-SMZ (26%). Small numbers of strains were resistant to levofloxacin (0.7%), trovafloxacin (0.4%) and grepafloxacin (1.3%) where as all strains remained uniformly susceptible to quinupristin/dalfopristin and BMS284756 (MIC(90), 0.06 mg/l), a new desfluoroquinolone. beta-lactamases were, produced by 20% H. influenzae isolates and only rare strains showed intrinsic resistance to amoxycillin. Other beta-lactam agents showed good activity with rates of resistance less than 2% and all isolates showed susceptibility to cefixime, ceftibuten, cefepime and cefotaxime. Rates of resistance to tetracycline and chloramphenicol were also relatively low at 3%. The majority (98%) of M. catarrhalis isolates was found to be beta-lactamase-positive and resistant to penicillins, however, resistance to erythromycin and tetracycline was also low at 1.8%. Both H. influenzae and M. catarrhalis isolates were uniformly susceptible to the new desfluoroquinolone and tested fluoroquinolones.

PMID 11850165  Int J Antimicrob Agents. 2002 Feb;19(2):125-32.
著者: U B Schaad, S Suter, A Gianella-Borradori, J Pfenninger, R Auckenthaler, O Bernath, J J Cheseaux, J Wedgwood
雑誌名: N Engl J Med. 1990 Jan 18;322(3):141-7. doi: 10.1056/NEJM199001183220301.
Abstract/Text To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission. After 18 to 36 hours of therapy, cultures of cerebrospinal fluid remained positive for 1 of the 52 children (2 percent) receiving ceftriaxone for whom cultures were available and 6 of 52 (12 percent) receiving cefuroxime (P = 0.11). In both groups the mean duration of antibiotic therapy was 10 days. The clinical responses to therapy were similar in the two treatment groups, and all 106 children were cured. Reversible biliary pseudolithiasis was detected by serial abdominal ultrasonography only in the children treated with ceftriaxone (16 of 35 vs. 0 of 35; P less than 0.001). The treatment of three children was switched from ceftriaxone to alternative antibiotics because these children had upper abdominal pain. Other side effects were infrequent in both groups. At follow-up examination two months later, moderate-to-profound hearing loss was present in two children (4 percent) treated with ceftriaxone and in nine (17 percent) treated with cefuroxime (P = 0.05); other neurologic abnormalities were similar in the two treatment groups. We conclude that ceftriaxone is superior to cefuroxime for the treatment of acute bacterial meningitis in children and that the benefits of milder hearing impairment and more rapid sterilization of the cerebrospinal fluid with ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.

PMID 2403654  N Engl J Med. 1990 Jan 18;322(3):141-7. doi: 10.1056/NE・・・
著者: Heather E Clauss, Bennett Lorber
雑誌名: Curr Infect Dis Rep. 2008 Jul;10(4):300-6.
Abstract/Text The foodborne pathogen Listeria monocytogenes has a particular tropism for the central nervous system and can produce infection in the meninges and brain substance. Well-recognized clinical syndromes include meningitis, brain abscess, rhombencephalitis, and spinal cord abscess; simultaneous infection of the meninges and brain is common. Although it is an uncommon cause of infection in the population at large, L. monocytogenes is an important cause of central nervous system infection in those with impaired cell-mediated immunity, whether due to underlying disease or treatment with immunosuppressive therapeutic agents; it is the etiology in 20% of bacterial meningitis cases in neonates and in 20% of cases in those older than 50 years. Ampicillin is considered the treatment of choice, and trimethoprim-sulfamethoxazole is recommended for those allergic to penicillin. At-risk patients should be advised to avoid unpasteurized milk and soft cheeses along with deli-style, ready-to-eat prepared meats, particularly poultry products.

PMID 18765103  Curr Infect Dis Rep. 2008 Jul;10(4):300-6.
著者: I W Fong, K B Tomkins
雑誌名: Rev Infect Dis. 1985 Sep-Oct;7(5):604-12.
Abstract/Text Pseudomonas aeruginosa meningitis is a rare disease and the optimal antibiotic therapy for this condition is not well established. Results of therapy using various regimens reported since 1960 are reviewed. Ceftazidime, an investigational cephalosporin with potent antipseudomonal activity, has been used to treat P. aeruginosa meningitis in Europe and North America. The results in 24 patients are analyzed here. Most patients had failed to respond to other regimens before commencing therapy with ceftazidime. Nineteen (79.2%) of these patients were cured, and only three (12.5%) were considered therapeutic failures. Hence, ceftazidime is a useful agent in the treatment of gram-negative bacillary meningitis and may be superior to other cephalosporins on the market for the treatment of pseudomonas meningitis. Since development of resistance is a concern, however, it may be prudent to use a concomitant parenteral aminoglycoside with ceftazidime for the first week in the treatment of P. aeruginosa meningitis.

PMID 3903939  Rev Infect Dis. 1985 Sep-Oct;7(5):604-12.
著者: J M Rousseau, B Soullié, T Villevielle, J L Koeck
雑誌名: J Trauma. 2001 May;50(5):971.
Abstract/Text
PMID 11379596  J Trauma. 2001 May;50(5):971.
著者: K P Klugman, R Dagan
雑誌名: Antimicrob Agents Chemother. 1995 May;39(5):1140-6.
Abstract/Text Broad-spectrum cephalosporins are drugs of choice for the treatment of meningitis in communities which can afford them. The emergence of cephalosporin-resistant pneumococci demands the clinical trial of alternate agents. Carbapenems are active against the bacteria causing meningitis, but the use of imipenem-cilastatin was frustrated by drug-associated seizures. The safety and efficacy of meropenem, a new carbapenem, were compared to those of cefotaxime in a prospective randomized trial of 190 children with bacterial meningitis. Seizures occurred within 24 h before antibiotic therapy in 16 of 98 patients (16%) randomized to receive meropenem and in 6 of 92 patients (7%) randomized to receive cefotaxime. In patients without seizures before therapy, seizures occurred during therapy in 5 of 82 patients (6%) receiving meropenem and in 1 of 86 patients (1%) receiving cefotaxime (95% confidence interval: -0.7%, 10.6%). None were thought to be drug related. Twenty-four meropenem-treated patients (24%) and 11 cefotaxime-treated patients (12%) had neurological abnormalities before therapy. In patients without pretherapy neurological abnormalities, these abnormalities were present after treatment in 4 of 74 meropenem-treated patients (5%) and in 2 of 81 cefotaxime-treated patients (2%) (95% confidence interval: -3.2%, 9.1%). Of 75 meropenem-treated and 64 cefotaxime-treated patients with pretherapy positive cerebrospinal-fluid cultures, 68 and 59, respectively, had repeat lumbar punctures. Bacterial eradication was found to be 100% in both groups. Our data suggest that meropenem may be a carbapenem agent that is well tolerated and effective in the treatment of bacterial meningitis.

PMID 7625802  Antimicrob Agents Chemother. 1995 May;39(5):1140-6.
著者: Bettina Pfausler, Heinrich Spiss, Ronny Beer, Andreas Kampl, Klaus Engelhardt, Maria Schober, Erich Schmutzhard
雑誌名: J Neurosurg. 2003 May;98(5):1040-4. doi: 10.3171/jns.2003.98.5.1040.
Abstract/Text OBJECT: Staphylococcal ventriculitis may be a complication in temporary external ventricular drains (EVDs). The limited penetration of vancomycin into the cerebrospinal fluid (CSF) is well known; the pharmacodynamics and efficacy of systemically compared with intraventricularly administered vancomycin is examined in this prospective study.
METHODS: Ten patients in whom EVDs were implanted to treat intracranial hemorrhage and who were suffering from drain-associated ventriculitis were randomized into two treatment groups. Five of these patients (median age 47 years) were treated with 2 g/day vancomycin administered intravenously (four infusions/day, Group 1), and the other five(median age 49 years) received 10 mg vancomycin intraventricularly once daily (Group 2). Vancomycin levels were measured in serum and CSF six times a day. The maximum vancomycin level in CSF was 1.73 +/- 0.4 micro/ml in Group 1 and 565.58 +/- 168.71 microg/ml 1 hour after vancomycin application in Group 2 (mean +/- standard deviation). Vancomycin levels above the recommended trough level of 5 microg/ml in CSF were never reached in Group 1, whereas in Group 2 they below the trough level (3.74 +/- 0.66 microg/ml) only at 21 hours after intraventricular vancomycin application. The vancomycin level in the serum was constant within therapeutic levels in Group 1, whereas in Group 2 in most instances vancomycin was almost below a measurable concentration. In both groups bacteriologically and laboratory-confirmed CSF clearance could be obtained.
CONCLUSIONS: Intraventricular vancomycin application is a safe and efficacious treatment modality in drain-associated ventriculitis, with much higher vancomycin levels being achieved in the ventricular CSF than by intravenous administration.

PMID 12744364  J Neurosurg. 2003 May;98(5):1040-4. doi: 10.3171/jns.20・・・
著者: Karen Ng, Vincent H Mabasa, Ivy Chow, Mary H H Ensom
雑誌名: Neurocrit Care. 2014 Feb;20(1):158-71. doi: 10.1007/s12028-012-9784-z.
Abstract/Text Central nervous system infections requiring treatment with intraventricular (IVT) vancomycin are becoming increasingly common with advent of intracranial devices and increasing prevalence of multi-drug resistant and nosocomial organisms. Administering vancomycin via IVT route bypasses the blood-brain barrier to allow localized and controlled delivery directly to the desired site of action, achieving high concentrations for more reliable bactericidal action. This article systematically reviews current literature on IVT vancomycin in adults, compiles current knowledge, and integrates available evidence to serve as a practical reference.Medline (1946-July 2012), Embase (1974-July 2012), and International Pharmaceutical Abstracts (1970-July 2012) were searched using terms vancomycin, intraventricular, shunt infection, cerebrospinal fluid, and intraventriculitis. Seventeen articles were included in this review. Indications for IVT vancomycin included meningitis unresponsive to intravenous antibiotics, ventriculitis, and intracranial device infections. No serious adverse effects following IVT vancomycin have been reported. Dosages reported in literature ranged from 0.075-50 mg/day, with the most evidence for dosages of 5 to 20 mg/day. Duration of therapy most commonly ranged from 7 to 21 days. Therapeutic drug monitoring was reported in 11 studies, with CSF vancomycin levels varying widely from 1.1 to 812.6 mg/L, without clear relationships between CSF levels and efficacy or toxicity. Using IVT vancomycin to treat meningitis, ventriculitis, and CNS device-associated infections appears safe and effective based on current evidence. Optimal regimens are still unclear, and dosing of IVT vancomycin requires intricate consideration of patient specific factors and their impact on CNS pathophysiology. Higher-quality clinical trials are necessary to characterize the disposition of vancomycin within CNS, and to determine models for various pathophysiological conditions to facilitate better understanding of effects on pharmacokinetic and pharmacodynamic parameters.

PMID 23090839  Neurocrit Care. 2014 Feb;20(1):158-71. doi: 10.1007/s12・・・
著者: Thomas Tängdén, Per Enblad, Måns Ullberg, Jan Sjölin
雑誌名: Clin Infect Dis. 2011 Jun;52(11):1310-6. doi: 10.1093/cid/cir197. Epub 2011 May 2.
Abstract/Text BACKGROUND: Gram-negative bacillary (GNB) ventriculitis and meningitis are rare but serious complications after neurosurgery. Prospective studies on antibiotic treatment for these infections are lacking, and retrospective reports are sparse. At our hospital in Uppsala, Sweden, meropenem has been recommended as empirical therapy since 1996, with the addition of intraventricular gentamicin in cases that do not respond satisfactorily to treatment. In this study, we retrospectively compare the efficacy of combination treatment with intraventricular gentamicin to that of systemic antibiotics alone. In addition, we report our experience of meropenem for the treatment of GNB ventriculomeningitis.
METHODS: Adult consecutive patients with gram-negative bacteria isolated from cerebrospinal fluid during a 10-year period and with postneurosurgical GNB ventriculitis or meningitis were included retrospectively. Data were abstracted from the medical records.
RESULTS: Thirty-one patients with neurosurgical GNB ventriculitis or meningitis and follow-up for 3 months were identified. The main intravenous therapies were meropenem (n = 24), cefotaxime (n = 3), ceftazidime (n = 2), imipenem (n = 1), and trimethoprim-sulfamethoxazole (n = 1). Thirteen patients were given combination treatment with appropriate intraventricular gentamicin. These patients had a higher cure rate and a lower relapse rate than did those treated with intravenous antibiotics alone (P = .03). Relapse occurred in 0 of 13 patients treated intraventricularly and in 6 of 18 patients treated with systemic antibiotics alone. The mortality rate was 19%; 3 patients in each group died, but in no case was death considered to be attributable to meningitis.
CONCLUSIONS: Our results support combination treatment with intraventricular gentamicin for postneurosurgical GNB ventriculomeningitis. Meropenem seems to be an effective and safe alternative for the systemic antibiotic treatment of these neurointensive care infections.

PMID 21540208  Clin Infect Dis. 2011 Jun;52(11):1310-6. doi: 10.1093/c・・・
著者: Jui-Hsing Wang, Po-Chang Lin, Chia-Hui Chou, Cheng-Mao Ho, Kuo-Hsi Lin, Chia-Ta Tsai, Jen-Hsien Wang, Chih-Yu Chi, Mao-Wang Ho
雑誌名: J Microbiol Immunol Infect. 2014 Jun;47(3):204-10. doi: 10.1016/j.jmii.2012.08.028. Epub 2012 Nov 30.
Abstract/Text BACKGROUND: Postneurosurgical Gram-negative bacillary meningitis (GNBM) or ventriculitis is a serious issue. Intraventricular (IVT) therapy has been applied; however, its effectiveness remains controversial, and the adverse drug effects are considerable.
METHODS: The demographic data, treatment strategies, and clinical outcomes of patients with postneurosurgical GNBM or ventriculitis were recorded.
RESULTS: From 2003 to 2011, data on 127 episodes of infection in 109 patients were collected, and 15 episodes in 14 patients were treated using a sequential combination of intravenous antibiotics and IVT therapy; others received intravenous antibiotics alone. The average age of patients who received a sequential combination with IVT therapy was 48.9 years, and 71.4% of the patients were men. The regimens used for IVT therapies included gentamicin (n = 4), amikacin (n = 7), and colistin (n = 4). After meningitis had been diagnosed, the average period that elapsed before initiation of IVT therapy was 25.4 days, and the average duration of IVT therapy was 13.3 days. The most frequently isolated pathogen from cerebrospinal fluid (CSF) was Acinetobacter baumannii, followed by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Serratia marcescens. The cure rate was 73.3%. Of note, the mean period to sterilize the CSF after appropriate IVT antibiotic treatment was 6.6 days. There were no incidents of seizure or chemical ventriculitis during this IVT therapy.
CONCLUSION: The findings of this study suggest that IVT antibiotic therapy is a useful option in the treatment of postneurosurgical GNBM or ventriculitis, especially for those with a treatment-refractory state.

Copyright © 2012. Published by Elsevier B.V.
PMID 23201321  J Microbiol Immunol Infect. 2014 Jun;47(3):204-10. doi:・・・
著者: Sachin S Shah, Arne Ohlsson, Vibhuti S Shah
雑誌名: Cochrane Database Syst Rev. 2012 Jul 11;(7):CD004496. doi: 10.1002/14651858.CD004496.pub3. Epub 2012 Jul 11.
Abstract/Text BACKGROUND: Neonatal meningitis may be caused by bacteria, especially gram-negative bacteria, which are difficult to eradicate from the cerebrospinal fluid (CSF) using safe doses of antibiotics. In theory, intraventricular administration of antibiotics would produce higher antibiotic concentrations in the CSF than intravenous administration alone, and eliminate the bacteria more quickly. However, ventricular taps may cause harm.
OBJECTIVES: To assess the effectiveness and safety of intraventricular antibiotics (with or without intravenous antibiotics) in neonates with meningitis (with or without ventriculitis) as compared to treatment with intravenous antibiotics alone.
SEARCH METHODS: The Cochrane Library, Issue 2, 2007; MEDLINE; EMBASE; CINAHL and Science Citation Index were searched in June 2007. The Oxford Database of Perinatal Trials was searched in June 2004. Pediatric Research (abstracts of proceedings) were searched (1990 to April 2007) as were reference lists of identified trials and personal files. No language restrictions were applied.This search was updated in May 2011.
SELECTION CRITERIA: Selection criteria for study inclusion were: randomised or quasi-randomised controlled trials in which intraventricular antibiotics with or without intravenous antibiotics were compared with intravenous antibiotics alone in neonates (< 28 days old) with meningitis. One of the following outcomes was required to be reported: mortality during initial hospitalisation; neonatal or infant mortality, or both; neurodevelopmental outcome; duration of hospitalisation; duration of culture positivity of CSF and side effects.
DATA COLLECTION AND ANALYSIS: All review authors abstracted information for outcomes reported and one review author checked for discrepancies and entered data into RevMan 5.1. Risk ratio (RR), risk difference (RD), number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH), and mean difference (MD), using the fixed-effect model are reported with 95% confidence intervals (CI).
MAIN RESULTS: The updated search in June 2011 did not identify any new trials. One study is included in the review. This study assessed the effect of intraventricular gentamicin in a mixed population of neonates (69%) and older infants (31%) with gram-negative meningitis and ventriculitis. Mortality was statistically significantly higher in the group that received intraventricular gentamicin in addition to intravenous antibiotics compared to the group receiving intravenous antibiotics alone (RR 3.43; 95% CI 1.09 to 10.74; RD 0.30; 95% CI 0.08 to 0.53); NNTH 3; 95% CI 2 to 13). Duration of CSF culture positivity did not differ significantly (MD -1.20 days; 95% CI -2.67 to 0.27).
AUTHORS' CONCLUSIONS: In one trial that enrolled infants with gram-negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a three-fold increased RR for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics as tested in this trial should be avoided. Further trials comparing these interventions are not justified in this population.

PMID 22786491  Cochrane Database Syst Rev. 2012 Jul 11;(7):CD004496. d・・・
著者: H E James, J W Walsh, H D Wilson, J D Connor, J R Bean, P A Tibbs
雑誌名: Neurosurgery. 1980 Nov;7(5):459-63. doi: 10.1227/00006123-198011000-00006.
Abstract/Text Thirty patients who met the rigid criteria for a prospective randomized study of cerebrospinal fluid (CSF) shunt infections underwent therapy with the three currently advocated treatment modalities to determine the efficacy of each form of therapy. Ten patients (Group A) underwent shunt removal and, in addition to receiving systemic antibiotics, were treated by either external ventricular drainage or intermittent ventricular taps for decompression and antibiotic administration; 10 patients (Group B) were treated by removal and immediate replacement of the shunt and intrashunt antibiotic therapy; and 10 patients (Group C) received antibiotics without removal or replacement of the shunt. All patients were given intravenous and intraventricular antibiotics as follows: in Group A, antibiotics were given by both the intravenous and the intraventricular routes for a minimal period of 7 days; in Group B, intravenous antibiotics were administered for a minimal period of 3 weeks and twice daily intraventricular antibiotics were given for a minimal period of 2 weeks; in Group C, intravenous antibiotics were administered for a minimal period of 3 weeks and twice daily intraventricular antibiotics were given for a minimal period of 2 weeks. In all patients, CSF was obtained from the shunt and cultured 48 hours after the cessation of antibiotic therapy, and the cultures were repeated within 4 months of the completion of treatment. All patients in Group A and 9 of 10 patients in Group B were treated successfully. They were clinically asymptomatic, and cultures after treatment were sterile. However, only 3 patients in Group C responded to treatment. The remaining patients of Group C had persistent infections requiring additional therapy. The mean follow-up of the study group was 23 +/- 14 (SD) months. The mean hospitalization time for the study group was 33 +/- 21 days; the hospitalization time was 24.7 +/- 17 days for Group A alone, 32.7 +/- 8 days for Group B, and 47 +/- 37 days Group C.

PMID 7003434  Neurosurgery. 1980 Nov;7(5):459-63. doi: 10.1227/000061・・・
著者: Katia Orvin, Efraim Bilavsky, Eran Weiner, Dror S Shouval, Jacob Amir
雑誌名: Int J Infect Dis. 2009 May;13(3):e101-3. doi: 10.1016/j.ijid.2008.07.008. Epub 2008 Oct 23.
Abstract/Text A case of Streptococcus pneumoniae meningitis in a possibly immune-compromised child with a ventriculoatrial shunt is described. The infection was successfully eradicated by treatment with intravenous ceftriaxone and rifampicin, without removal of the shunt.

PMID 18948047  Int J Infect Dis. 2009 May;13(3):e101-3. doi: 10.1016/j・・・
著者: Caroline L Trotter, Andrew J Fox, Mary E Ramsay, Francesca Sadler, Stephen J Gray, Richard Mallard, Edward B Kaczmarski
雑誌名: J Med Microbiol. 2002 Oct;51(10):855-60. doi: 10.1099/0022-1317-51-10-855.
Abstract/Text Penicillin has been the mainstay of treatment for meningococcal disease. Isolates of Neisseria meningitidis that are less susceptible to penicillin have been reported in several countries and in recent years have become more common. The clinical significance of this reduced susceptibility has not been investigated on a large scale. Hence, N. meningitidis isolates from culture-confirmed cases of meningococcal disease in England and Wales, between 1993 and 2000, were routinely serogrouped, serotyped and tested for susceptibility to penicillin. These data were linked to death registrations and analysed retrospectively. The changing trends in susceptibility were described and multivariate logistic regression was used to examine associations between strain characteristics and fatal outcome. The frequency of N. meningitidis isolates less susceptible to penicillin increased from < 6% in 1993 to > 18% in 2000. In particular, isolates expressing serogroup C with serotype 2b and serogroup W135 had a higher frequency of reduced penicillin susceptibility (49% and 55%, respectively). There was no evidence of an association between fatal outcome and infection with a less penicillin-susceptible isolate. Fatal outcome was associated with serogroup and serotype, with the odds of death for cases infected with C:2a and B:2a strains three-fold higher when compared with the baseline. For this large dataset the serogroup and serotype of the infecting strain influenced mortality from meningococcal disease and may be markers for hypervirulence. No association was found between reduced penicillin susceptibility and fatal outcome, but the increasing frequency of isolates less susceptible to penicillin highlights the need for continued surveillance.

PMID 12435065  J Med Microbiol. 2002 Oct;51(10):855-60. doi: 10.1099/0・・・
著者: D A Drevets, B P Canono, P J Leenen, P A Campbell
雑誌名: Infect Immun. 1994 Jun;62(6):2222-8.
Abstract/Text The purpose of the experiments described here was to test whether membrane-impermeant antibiotics present in the extracellular milieu could kill bacteria within macrophages. For this, mouse macrophage hybrids and elicited mouse peritoneal macrophages first were allowed to phagocytose the facultative intracellular bacterium Listeria monocytogenes. The cells were incubated with or without gentamicin, and their bactericidal activity was measured. The results show that gentamicin caused normally nonbactericidal macrophages to kill L. monocytogenes. In addition, gentamicin caused listericidal cells to kill significantly more bacteria. To determine whether gentamicin accumulated within macrophages during culture, we tested whether lysates of macrophage hybrids cultured for 72 h in gentamicin-containing medium and then washed could kill Listeria cells. When cultured with 50 to 100 micrograms of gentamicin per ml, but not when cultured with 0 to 5 micrograms of gentamicin per ml, cell lysates were extremely listericidal, demonstrating the presence of intracellular gentamicin. Because gentamicin does not penetrate cell membranes, we hypothesized that it can be internalized by the cell through pinocytosis and can enter the same intracellular compartment as does phagocytosed L. monocytogenes. To test this, macrophages which had phagocytosed L. monocytogenes were incubated with the fluorochrome lucifer yellow to trace pinocytosed medium. About half of the Listeria cells within the macrophages were surrounded by lucifer yellow, indicating delivery of pinocytosed fluid, which could contain antibiotics, to phagosomes containing bacteria. The experiments described here indicate that membrane-impermeant antibiotics can enter macrophages and kill intracellular bacteria. Thus, the use of gentamicin in macrophage bactericidal assays can interfere with the results and interpretation of experiments designed to study macrophage bactericidal activity.

PMID 8188344  Infect Immun. 1994 Jun;62(6):2222-8.
著者: Ajaree Rayanakorn, Hooi-Leng Ser, Priyia Pusparajah, Kok-Gan Chan, Bey Hing Goh, Tahir Mehmood Khan, Surasak Saokaew, Shaun Wen Huey Lee, Learn-Han Lee
雑誌名: PLoS One. 2020;15(5):e0232947. doi: 10.1371/journal.pone.0232947. Epub 2020 May 29.
Abstract/Text OBJECTIVE: To compare relative efficacy of different antibiotic therapies either with or without the addition of corticosteroids among adult patients with acute bacterial meningitis on all-cause mortality, neurological complications and any hearing loss.
METHODS: We searched nine databases from inception to 8 February 2018 for randomized controlled trials evaluating pharmacological interventions and clinical outcomes in adult bacterial meningitis. An updated search from 9 February to 9 March 2020 was performed, and no new studies met the inclusion criteria. Study quality was assessed using the revised Cochrane Risk of Bias Tool. The Grading of Recommendations Assessment, Development and Evaluation system was used for quality of evidences evaluation. Meta-analyses were conducted to estimate the risk ratio with 95% confidence interval for both direct and indirect comparisons on the primary outcomes of all-cause mortality, neurologic sequelae and any hearing loss. The study was registered in PROSPERO (CRD42018108062).
RESULTS: Nine RCTs were included in systematic review, involving 1,002 participants with a mean age ranging between 25.3 to 50.56 years. Six RCTs were finally included in the network-meta analysis. No significant difference between treatment was noted in meta-analysis. Network meta-analysis suggests that corticosteroids in combination with antibiotic therapy was more effective in reducing the risk of any hearing loss compared to mono antibiotic therapy (RR 0.64; 95%CI, 0.45 to 0.91, 4 RCTs, moderate certainty of evidence). Numerical lower risk of mortality and neurological complications was also shown for adjunctive corticosteroids in combination with antibiotic therapy versus mono antibiotic therapy (RR 0.65; 95%CI, 0.42 to 1.02, 6 RCTs, moderate certainty of evidence; RR 0.75; 95%CI, 0.47 to 1.18, 6 RCTs, moderate certainty of evidence). No differences were noted in the adverse events between different therapies. The overall certainty of evidence was moderate to very low for all primary outcomes examined.
CONCLUSIONS: Results of this study suggest that corticosteroids therapy in combination with antibiotic is more effective than mono antibiotic therapy in reducing the risk of any hearing loss in adult patients with acute bacterial meningitis. More well-design RCTs to investigate relative effective treatments in acute bacterial meningitis particularly in adult population should be mandated to aid clinicians in treatment recommendations.

PMID 32469959  PLoS One. 2020;15(5):e0232947. doi: 10.1371/journal.pon・・・
著者: Aaron M Cook, G Morgan Jones, Gregory W J Hawryluk, Patrick Mailloux, Diane McLaughlin, Alexander Papangelou, Sophie Samuel, Sheri Tokumaru, Chitra Venkatasubramanian, Christopher Zacko, Lara L Zimmermann, Karen Hirsch, Lori Shutter
雑誌名: Neurocrit Care. 2020 Jun;32(3):647-666. doi: 10.1007/s12028-020-00959-7.
Abstract/Text BACKGROUND: Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety.
METHODS: The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy.
RESULTS: The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy.
CONCLUSION: The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.

PMID 32227294  Neurocrit Care. 2020 Jun;32(3):647-666. doi: 10.1007/s1・・・
著者: A S Daoud, A Batieha, M Al-Sheyyab, F Abuekteish, A Obeidat, T Mahafza
雑誌名: Eur J Pediatr. 1999 Mar;158(3):230-3.
Abstract/Text UNLABELLED: A clinical trial was conducted to determine whether dexamethasone as adjunctive therapy alters the outcome of bacterial meningitis in neonates. Fifty-two full-term neonates with bacterial meningitis were enrolled in a prospective study. Infants were alternately assigned to receive either dexamethasone or not. Twenty-seven received dexamethasone in addition to standard antibiotic treatment and 25 received antibiotics alone. Dexamethasone therapy was started 10-15 min before the first dose of antibiotics in a dose of 0.15 mg/kg per 6 h for 4 days. Baseline characteristics, clinical and laboratory features in the two groups were virtually similar. Both groups showed a similar clinical response and similar frequency of mortality and sequelae. Six (22%) babies in the treatment group died compared to 7 (28%) in the control group (P = 0.87). At follow up examinations up to the age of 2 years, 6 (30%) of dexamethasone recipients and 7 (39%) of the control group had mild or moderate/severe neurological sequelae. Audiological sequelae were seen in two neonates in the dexamethasone group compared to one in the control group.
CONCLUSION: Adjunctive dexamethasone therapy does not improve the outcome of neonatal bacterial meningitis.

PMID 10094445  Eur J Pediatr. 1999 Mar;158(3):230-3.
著者: Emma Cb Wall, Katherine Mb Ajdukiewicz, Hanna Bergman, Robert S Heyderman, Paul Garner
雑誌名: Cochrane Database Syst Rev. 2018 Feb 6;2:CD008806. doi: 10.1002/14651858.CD008806.pub3. Epub 2018 Feb 6.
Abstract/Text BACKGROUND: Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.This is an update of a Cochrane Review first published in 2013.
OBJECTIVES: To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability.
SEARCH METHODS: We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015).
SELECTION CRITERIA: Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence.
MAIN RESULTS: We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low-certainty evidence).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low-certainty evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate-certainty evidence).Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate-certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS: Glycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness.

PMID 29405037  Cochrane Database Syst Rev. 2018 Feb 6;2:CD008806. doi:・・・
著者: Tuula Pelkonen, Irmeli Roine, Manuel Leite Cruzeiro, Anne Pitkäranta, Matti Kataja, Heikki Peltola
雑誌名: Lancet Infect Dis. 2011 Aug;11(8):613-21. doi: 10.1016/S1473-3099(11)70055-X. Epub 2011 May 5.
Abstract/Text BACKGROUND: New antimicrobials or adjunctive treatments have not substantially reduced mortality from acute childhood bacterial meningitis. Paracetamol seems to have beneficial effects in bacteraemic adults and some experts recommend initial slow β-lactam infusion. We investigated whether these treatments had benefits in children with bacterial meningitis.
METHODS: We did a prospective, double-blind, single-centre study with a two-by-two factorial design in Luanda, Angola. 723 participants aged 2 months to 13 years were randomly assigned two 12 h intravenous infusions, without loading doses, of 125 mg/kg bodyweight cefotaxime (total dose 250 mg/kg) given over 24 h, or 250 mg/kg bodyweight cefotaxime given as four boluses, one every 6 h over 24 h. Patients also received oral paracetamol at an initial dose of 30 mg/kg then 20 mg/kg every 6 h for 48 h or placebo. Two primary endpoints, death or severe neurological sequelae and deafness, were analysed by intention to treat. The study was registered as ISRCTN62824827.
FINDINGS: 183 patients were assigned cefotaxime infusion plus paracetamol and 180 patients to each of the other three treatment groups. Causative agents were identified in 63% of cases and were mostly Haemophilus influenzae type b, Streptococcus pneumoniae, or Neisseria meningitidis. Death or severe neurological sequelae were seen in 340 (47%) of 723 children and deafness in 45 (12%) of 374 tested, both distributed similarly across treatment groups. In a predefined subgroup analysis of death or any sequelae, by causative agent, a benefit was seen in favour of infusion over bolus in children with pneumococcal meningitis (infusion plus placebo, odds ratio 0·18, 95% CI 0·03-0·90, p=0·04). A similar effect was seen for children receiving cefotaxime infusion plus paracetamol, but the difference was not significant (OR 0·22, 95% CI 0·04-1·09, p=0·06). A post-hoc analysis suggested that cefotaxime infusion plus paracetamol lowered mortality at least during the first 3 days, irrespective of cause.
INTERPRETATION: Although no tested regimen improved the final outcomes of these very ill children, studies of longer courses of β-lactam infusion plus paracetamol seem warranted.
FUNDING: The Päivikki and Sakari Sohlberg, the Sigrid Jusélius, and the Paediatric Research Foundations, and the daily newspaper Helsingin Sanomat.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 21550313  Lancet Infect Dis. 2011 Aug;11(8):613-21. doi: 10.1016/・・・
著者: Elizabeth M Molyneux, Kondwani Kawaza, Ajib Phiri, Yamikani Chimalizeni, Limangeni Mankhambo, Edward Schwalbe, Matti Kataja, Paul Pensulo, Lucy Chilton, Heikki Peltola
雑誌名: Pediatr Infect Dis J. 2014 Feb;33(2):214-6. doi: 10.1097/INF.0000000000000122.
Abstract/Text We investigated the benefit of 2 candidate adjunctive therapies in bacterial meningitis: glycerol, which has shown promise in earlier studies, and acetaminophen, which is reportedly beneficial in adult septicemia. In a hospital in Blantyre, Malawi, we enrolled 360 children aged ≥ 2 months with proven bacterial meningitis (36% HIV infected) in a double-blind, randomized, placebo-controlled trial of glycerol and acetaminophen in a 2 × 2 factorial design. Of 4 groups, first group received oral glycerol, second received rectal acetaminophen, third received both therapies and the fourth received placebos only. Adjuvant therapies were given for the first 48 hours of antibiotic therapy. Endpoints were mortality and neurological sequelae. Baseline findings were similar across all groups, except that many children had prior antibiotics in the acetaminophen group and many were anemic in the acetaminophen and glycerol group. Outcomes were similar for all groups. We found no benefit from oral glycerol or rectal acetaminophen in, mostly pneumococcal, meningitis in Malawian children.

PMID 24136368  Pediatr Infect Dis J. 2014 Feb;33(2):214-6. doi: 10.109・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから