インフルエンザ菌b型(Hib)ワクチンおよび7価肺炎球菌結合型ワクチン(PCV7)導入が侵襲性細菌感染症に及ぼす効果について IASR Vol.33 p71-72: 20123月号.
Naruhiko Ishiwada, Haruka Hishiki, Koo Nagasawa, Sachiko Naito, Yasunori Sato, Bin Chang, Yuko Sasaki, Kouji Kimura, Makoto Ohnishi, Keigo Shibayama
The incidence of pediatric invasive Haemophilus influenzae and pneumococcal disease in Chiba prefecture, Japan before and after the introduction of conjugate vaccines.
Vaccine. 2014 Sep 22;32(42):5425-31. doi: 10.1016/j.vaccine.2014.07.100. Epub 2014 Aug 12.
Abstract/Text
The Haemophilus influenzae type b (Hib) vaccine and the heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in 2008 and 2010, respectively. In 2011, immunization with these two vaccines was encouraged throughout Japan through a governmental program. Children treated in Chiba prefecture for culture-proven invasive H. influenzae disease (IHiD) and invasive Streptococcus pneumoniae disease (IPD) were identified in a prefectural surveillance study from 2008 to 2013. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare the 3 years before and after governmental financial support for vaccination. The average number of IHiD and IPD cases among children <5 years of age in 2011-2013 decreased 84% (IRR: 0.16, 95% CI: 0.09-0.26, p<0.0001) and 51% (IRR: 0.49, 95% CI: 0.37-0.63, p<0.0001) compared with those occurring in 2008-2010. The most common non-PCV7 serotype encountered in 2011 and 2013 was 19A. After governmental subsidization of Hib and PCV7 vaccination, IHiD and IPD decreased in Chiba prefecture, Japan. Continuous surveillance is necessary to determine the effectiveness of these two vaccines and for detection of emerging invasive serotypes.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Shigeru Suga, Bin Chang, Kazutoyo Asada, Hideki Akeda, Junichiro Nishi, Kenji Okada, Hiroshi Wakiguchi, Akihiko Maeda, Megumi Oda, Naruhiko Ishiwada, Akihiko Saitoh, Tomohiro Oishi, Mitsuaki Hosoya, Takehiro Togashi, Kazunori Oishi, Toshiaki Ihara
Nationwide population-based surveillance of invasive pneumococcal disease in Japanese children: Effects of the seven-valent pneumococcal conjugate vaccine.
Vaccine. 2015 Nov 9;33(45):6054-60. doi: 10.1016/j.vaccine.2015.07.069. Epub 2015 Jul 31.
Abstract/Text
BACKGROUND: In Japan, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2010. PCV13 has replaced PCV7 since November 2013.
METHODS: The effectiveness of PCV7 in protecting against invasive pneumococcal disease (IPD) in children aged <5 years was evaluated in a nationwide active population-based surveillance of IPD in 2008-2013 in 10 prefectures in Japan.
RESULTS: 1181 cases were identified; 711 pneumococcal strains were analyzed for serotyping and antimicrobial resistance. Compared with the baseline IPD incidence (25.0 per 100,000), a 98% decline in IPD caused by PCV7 serotypes was found after the introduction of PCV7. This was partially offset by an increased incidence of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes, resulting in a 57% decline in overall IPD incidence. Absolute increases in the incidence rates of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes were 2.1 and 2.8 per 100,000 during the study period, respectively. The proportion of meropenem-nonsusceptible strains, especially with serotypes 19A and 15A, increased significantly after PCV7 introduction.
CONCLUSIONS: Our data confirmed a 98% decline in IPD incidence caused by PCV7 serotypes in children aged <5 years and serotype replacement after PCV7 introduction. This shows the importance of continuing surveillance of serotypes responsible for IPD and their antimicrobial resistance in Japan.
Copyright © 2015 Elsevier Ltd. All rights reserved.
D B Polk, R W Steele
Bacterial meningitis presenting with normal cerebrospinal fluid.
Pediatr Infect Dis J. 1987 Nov;6(11):1040-2.
Abstract/Text
At a large children's hospital cases of bacterial meningitis with normal initial cerebrospinal fluid determinations other than culture or antigen detection assays were reviewed in an attempt to determine clinical or other laboratory findings accompanying this presentation. During a 5-year period from January, 1980, through December, 1985, 7 of 261 pediatric meningitis patients (2.7%) fulfilled these criteria. Ages ranged from 3 weeks to 18 months. All 7 patients were hospitalized for observation with all but 1 begun on empiric antibiotic therapy. Laboratory parameters such as a complete blood count, sedimentation rate or C-reactive protein did not influence decisions for management. Cerebrospinal fluid antigen detection assays were negative in all but one patient with pneumococcal meningitis. Review of these cases did not reveal unique indicators for bacterial meningitis. The results emphasize that the physician must rely on clinical judgment in initiating empiric antimicrobial therapy once apparently normal cerebrospinal fluid parameters are observed.
JAID/JSC感染症治療ガイド委員会 JAID/JSC感染症治療ガイド2014 ライフサイエンス出版 東京 2014.
細菌性髄膜炎診療ガイドライン作成委員会 細菌性髄膜炎診療ガイドライン2014 南江堂 東京 2014.
Allan R Tunkel, Barry J Hartman, Sheldon L Kaplan, Bruce A Kaufman, Karen L Roos, W Michael Scheld, Richard J Whitley
Practice guidelines for the management of bacterial meningitis.
Clin Infect Dis. 2004 Nov 1;39(9):1267-84. doi: 10.1086/425368. Epub 2004 Oct 6.
Abstract/Text
P B McIntyre, C S Berkey, S M King, U B Schaad, T Kilpi, G Y Kanra, C M Perez
Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988.
JAMA. 1997 Sep 17;278(11):925-31.
Abstract/Text
OBJECTIVE: To evaluate the effectiveness of dexamethasone in bacterial meningitis in the subcategories of causative organism and timing and nature of antibiotic therapy.
DATA SOURCES: MEDLINE, HEALTHLINE, and AIDSLINE were searched with the Medical Subject Headings "dexamethasone" and "meningitis" in any language. Bibliographies, conference abstracts, and the authors of identified studies were consulted.
STUDY SELECTION: Randomized, concurrently controlled trials of dexamethasone therapy in childhood bacterial meningitis published from 1988 to November 1996 were selected. Of 16 studies identified, 5 were not eligible.
DATA EXTRACTION: Data were extracted by means of standard outcomes in a protocol sent to all principal authors.
DATA SYNTHESIS: Random-effects meta-analysis models were used to obtain summary estimates. As the incidence of severe hearing loss differed significantly by organism among control subjects, organism-specific estimates were used. In Haemophilus influenzae type b meningitis, dexamethasone reduced severe hearing loss overall (combined odds ratio [OR], 0.31; 95% confidence interval [CI], 0.14-0.69). Similar ORs were obtained after studies were stratified by the timing of administration of dexamethasone (before or with antibiotics vs later) or by type of antibiotic (cefuroxime vs other). In pneumococcal meningitis, only studies in which dexamethasone was given early suggested protection, which was significant for severe hearing loss (combined OR, 0.09; 95% CI, 0.0-0.71) and approached significance for any neurological or hearing deficit (combined OR, 0.23; 95% CI, 0.04-1.05). For all organisms combined, the pooled OR suggested protection against neurological deficits other than hearing loss but was not significant (OR, 0.59; 95% CI, 0.34-1.02). Outcomes were similar in studies that used 2 vs more than 2 days of dexamethasone therapy. Adverse effects were not significantly increased with dexamethasone except for secondary fever. The incidence of gastrointestinal tract bleeding increased with longer duration of dexamethasone treatment (0.5% in controls, 0.8% with 2 days of treatment, 3.0% with 4 days of treatment).
CONCLUSIONS: The available evidence on adjunctive dexamethasone therapy confirms benefit for H influenzae type b meningitis and, if commenced with or before parenteral antibiotics, suggests benefit for pneumococcal meningitis in childhood. Limiting dexamethasone therapy to 2 days may be optimal.
Matthijs C Brouwer, Peter McIntyre, Jan de Gans, Kameshwar Prasad, Diederik van de Beek
Corticosteroids for acute bacterial meningitis.
Cochrane Database Syst Rev. 2010 Sep 8;(9):CD004405. doi: 10.1002/14651858.CD004405.pub3. Epub 2010 Sep 8.
Abstract/Text
BACKGROUND: In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response.
OBJECTIVES: To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 1), MEDLINE (1966 to February 2010), EMBASE (1974 to February 2010) and Current Contents (2001 to February 2010).
SELECTION CRITERIA: Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS: We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality.
MAIN RESULTS: Twenty-four studies involving 4041 participants were included. Similar numbers of participants died in the corticosteroid and placebo groups (18.0% versus 20.0%; risk ratio (RR) 0.92, 95% confidence interval (CI) 0.82 to 1.04, P = 0.18). There was a trend towards lower mortality in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.76, 95% CI 0.64 to 0.89) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced severe hearing loss in Haemophilus influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) and reduced mortality in Streptococcus pneumoniae meningitis (RR 0.84, 95% CI 0.72 to 0.98).In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high quality studies.Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events.
AUTHORS' CONCLUSIONS: Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.
G A Syrogiannopoulos, A N Lourida, M C Theodoridou, I G Pappas, G C Babilis, J J Economidis, D J Zoumboulakis, N G Beratis, N S Matsaniotis
Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen.
J Infect Dis. 1994 Apr;169(4):853-8.
Abstract/Text
Four-day dexamethasone therapy has been used to treat bacterial meningitis. This prospective, randomized study compared the effect of a 2-day versus a 4-day regimen. Children (n = 118, ages 2.5 months to 15 years) were evaluated; 50% of the cases were due to Neisseria meningitidis and 40% to Haemophilus influenzae type b. Patients were treated intravenously (iv) mainly with conventional antimicrobial therapy and were randomly assigned to receive dexamethasone, 0.15 mg/kg iv every 6 h for 2 or 4 days. The clinical response was similar for both dexamethasone regimens. The meningococcal meningitis patients survived without neurologic or audiologic sequelae. On long-term follow-up, neurologic sequelae or moderate or more severe unilateral or bilateral hearing impairment (or both) were found in 1.8% and 3.8% of patients treated with dexamethasone for 2 and 4 days, respectively. The 2-day regimen appears appropriate for the treatment of H. influenzae and meningococcal meningitis.
U B Schaad, U Lips, H E Gnehm, A Blumberg, I Heinzer, J Wedgwood
Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group.
Lancet. 1993 Aug 21;342(8869):457-61.
Abstract/Text
Routine use of steroids as adjunctive treatment of bacterial meningitis remains controversial. We have carried out a prospective, placebo-controlled, double-blind study of dexamethasone in 115 children with acute bacterial meningitis in Switzerland. The patients were randomly assigned to receive either placebo (n = 55) or dexamethasone (n = 60) in addition to optimum antibiotic treatment (100 mg/kg daily ceftriaxone). Dexamethasone therapy (0.4 mg/kg) was started 10 min before the first dose of ceftriaxone and given every 12 h for 2 days. Baseline demographic, clinical, and laboratory features of the two groups were similar. After 24 h treatment meningeal inflammation as shown by cerebrospinal fluid (CSF) glucose concentration was significantly less with dexamethasone than with placebo (mean increase in glucose 63 [76] vs 40 [75]%, p = 0.008). However, other indices of inflammation showed similar changes in both groups. Addition of dexamethasone did not affect the rate at which CSF became sterile. Both groups showed prompt clinical responses and similar frequencies of complications (15 vs 12%). Monitoring for possible adverse effects of dexamethasone revealed no abnormalities. At follow-up examinations 3, 9, and 15 months after hospital discharge, 9 (16%) of 55 placebo recipients and 3 (5%) of 60 dexamethasone recipients had one or more neurological or audiological sequelae (p = 0.066); the relative risk of sequelae was 3.27 (95% CI 0.93-11.47). Our results and those of similarly designed studies lead us to believe that adjunctive dexamethasone therapy improves outcome from bacterial meningitis in infants and children. We recommend its use, preferably in the dose regimen used in this study.
Jan de Gans, Diederik van de Beek, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators
Dexamethasone in adults with bacterial meningitis.
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
A S Daoud, A Batieha, M Al-Sheyyab, F Abuekteish, A Obeidat, T Mahafza
Lack of effectiveness of dexamethasone in neonatal bacterial meningitis.
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.
R D Feigin, G H McCracken, J O Klein
Diagnosis and management of meningitis.
Pediatr Infect Dis J. 1992 Sep;11(9):785-814.
Abstract/Text
American Academy of Pediatrics : Pickering LK, Baker CJ, Kimberlin DW, Long SS, ed. Red Book: 2012 Report of the Committee on Infectious Diseases, 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
J I Ward, D W Fraser, L J Baraff, B D Plikaytis
Haemophilus influenzae meningitis. A national study of secondary spread in household contacts.
N Engl J Med. 1979 Jul 19;301(3):122-6. doi: 10.1056/NEJM197907193010302.
Abstract/Text
To determine the risk of severe Haemophilus influenzae illness among household contacts of patients with H. influenzae meningitis, we studied prospective data obtained in 19 states from January 1, 1977, to June 30, 1978. H. influenzae meningitis was reported in 1403 patients, and 1147 (82 per cent) of the exposed families were investigated for the occurrence of H. influenzae disease within 30 days after its onset in the index patient. During this interval, nine of 1687 household contacts (0.5 per cent) under the age of six years had systemic disease confirmed to be caused by H. influenzae Type b. The risk in children less than one year of age was 6 per cent, and the risk in those less than four years of age was 2.1 per cent. None of 2624 contacts above the age of five was affected. In the 30 days after onset of meningitis, the risk of this infection alone, aside from other types of serious H. influenzae disease, is 585 times greater in household contacts than the age-adjusted risk in the general population. The risk of H. influenzae disease in household contacts under six years of age is similar to the risk of secondary meningococcal disease in all household contacts--indicating a need for effective antimicrobial prophylaxis.
J D Band, D W Fraser, G Ajello
Prevention of Hemophilus influenzae type b disease.
JAMA. 1984 May 11;251(18):2381-6.
Abstract/Text
To determine the efficacy of rifampin prophylaxis in eradication of oropharyngeal carriage of Hemophilus influenzae type b and prevention of secondary H influenzae type b disease, we conducted a multicenter placebo-controlled trial among selected persons with invasive H influenzae type b disease. Households and day-care classrooms were randomized so that their members received either rifampin (initially at a dose of 10 mg/kg/dose for two to four days [rifampin-10], but subsequently at 20 mg/kg/dose for four days [rifampin-20]) or placebo. Pretherapy H influenzae type b colonization rates were similar in the treatment groups. Therapy with either rifampin regimen significantly reduced carriage (rifampin-20, 97%; rifampin-10, 63%; placebo, 28%). New acquisition of carriage was also significantly reduced by either rifampin regimen (rifampin-20 or rifampin-10, 2% v placebo, 6%). No rifampin-resistant H influenzae type b isolates emerged after treatment. Four of 765 placebo-treated contacts experienced secondary disease in contrast to zero of 1,112 rifampin-treated contacts. Because chemoprophylaxis of close contacts with rifampin seems to reduce significantly the risk of secondary H influenzae type b disease, we recommend the administration of prophylaxis in households or day-care classrooms where children younger than 4 years have been exposed to the disease.
