今日の臨床サポート

炭疽

著者: 古宮伸洋 日本赤十字社和歌山医療センター

監修: 細川直登 亀田総合病院

著者校正済:2022/08/17
現在監修レビュー中
参考ガイドライン:
  1. 世界保健機構(World Health Organization:WHO):Anthrax in humans and animals, 4th ed.
  1. 予防接種諮問委員会(Advisory Committee on Immunization Practices:ACIP):Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep. 2019 Dec 13;68(4):1-14.
患者向け説明資料

概要・推奨   

  1. 吸入炭疽では、前駆期に抗菌薬治療を行うことで予後が大きく改善されるため、早期に診断、治療を開始することが重要である(推奨度1S)
  1. 吸入炭疽、重症全身性感染症ではフルオロキノロンを軸とする多剤併用療法が勧められる(推奨度1G)
  1. 曝露後の予防抗菌薬としてはシプロフロキサシン、レボフロキサシンあるいはドキシサイクリンが推奨される(推奨度1G)
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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。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※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、実際の保険適応の査定において保険適応及び保険適応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応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:
古宮伸洋 : 特に申告事項無し[2022年]
監修:細川直登 : 未申告[2022年]

改訂のポイント:
  1. 主に以下の点について加筆した。
  1. バイオテロなど炭疽菌曝露(吸入)の可能性がある場合は、以前は60日間の予防的抗菌薬投与が推奨されていたが、「適切にワクチンが併用された健常な成人の場合で42日間、それ以外では60日間の予防抗菌薬投与を行う」ことが新しく推奨された。
  1. 全身症状を伴う重症例への抗毒素治療として米国では抗毒素血清であるanthrax immune globulin intravenous(AIGIV)、モノクローナル抗体製剤であるobiltoxaximab(Anthim)とraxibacumab(ABthrax)が認可され、推奨されている。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 炭疽とは炭疽菌による感染症であり、汚染した哺乳類の摂食や皮革への曝露によって感染する疾患である。
  1. 炭疽菌(Bacillus anthracis)は、芽胞を形成するグラム陽性桿菌で、自然界では土壌中に存在するが、感染した野生および家畜の哺乳類からヒトに感染する場合が多い。
  1. 感染経路によって皮膚炭疽、吸入炭疽、消化管炭疽の3病型に分けられる。
  1. 皮膚炭疽は炭疽菌が直接皮膚に接触する経路、腸炭疽は汚染された食物を経口摂取する経路、吸入炭疽は炭疽菌芽胞を肺に吸入する経路で発生する。皮膚炭疽の特殊なタイプとして汚染されたヘロインの静脈注射による軟部組織感染がある。
  1. 自然発生する炭疽の95%以上は皮膚炭疽である[1]
  1. 炭疽はアジアやアフリカを中心に、世界中で年間2万~10万例程度発生していると推計されている[2]
  1. 発展途上国では毛皮を取り扱う業者での報告や、死んだ家畜の肉を食べて集団発生した報告がある。バイオテロリズムに使用されることがあり、2001年に米国で郵便物に炭疽菌芽胞が混入される事件が発生した[3]
  1. 炭疽は、感染症法の4類感染症に分類され、診断した医師は、ただちに最寄の保健所に届け出る必要がある。1995年以後は報告はない。
 
  1. 炭疽菌はバイオテロリズムに使用される可能性がある。
  1. 代表事例:1946年英国グリュナード島で炭疽菌爆弾の投下実験が行われた。
    1979年旧ソ連のSverdlovskにおいて、軍事施設からの炭疽菌流出事故により、68例が死亡した[4]
    1993年に東京都江東区亀戸において、オウム真理教団による炭疽菌撒布が試みられた。この時用いられた菌株は毒性が低く、技術的な問題からうまく撒布できなかったことから失敗に終わった[5]
    2001年に米国で郵便物に炭疽菌芽胞が混入され、22症例が発生した[1]
  1. まとめ:炭疽菌は生物兵器として開発されてきた歴史があり、バイオテロリズムに使用され得る。
問診・診察のポイント  
  1. 炭疽を疑う身体所見に加え、下記の病歴の聴取が重要である。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

Abstract/Text During the bioterrorism-associated anthrax investigation of 2001 in the United States, 11 patients were diagnosed with inhalational anthrax and 11 more with the cutaneous forms of the disease. Over 125,000 specimens were processed at laboratories of the Laboratory Response Network including those at the Centers for Disease Control and Prevention. Although the 2001 anthrax investigation initially began as a public health investigation, the forensic aspect quickly became a preeminent component of the investigation. Whereas a public health investigation aims primarily to identify the causative agent and its source, so that appropriate and timely control and preventative measures can be implemented, a forensic investigation goes further to associate the source of the causative agent with a specific individual or group. In addition to identification and molecular characterization of the causative agents, which are the crucial components of forensic microbiology, there are many other requirements and activities that need to be in place for investigators to successfully complete a forensic investigation. These activities include establishment of quality assurance/quality control criteria and regular proficiency testing for all laboratories where evidence is analyzed; additional and/or specialized training in handling and processing samples in accordance with forensic microbiology criteria, not only for first responders but also for laboratory and other public health scientists; and establishing and maintaining repositories and databases containing isolates of diverse temporal and geographic origins to provide a comparative and diverse background for investigators to identify and track the origin and source of such agents.

PMID 12808729
Wan-Jun Chen, Sheng-Jie Lai, Yang Yang, Kun Liu, Xin-Lou Li, Hong-Wu Yao, Yu Li, Hang Zhou, Li-Ping Wang, Di Mu, Wen-Wu Yin, Li-Qun Fang, Hong-Jie Yu, Wu-Chun Cao
Mapping the Distribution of Anthrax in Mainland China, 2005-2013.
PLoS Negl Trop Dis. 2016 Apr;10(4):e0004637. doi: 10.1371/journal.pntd.0004637. Epub 2016 Apr 20.
Abstract/Text BACKGROUND: Anthrax, a global re-emerging zoonotic disease in recent years is enzootic in mainland China. Despite its significance to the public health, spatiotemporal distributions of the disease in human and livestock and its potential driving factors remain poorly understood.
METHODOLOGY/PRINCIPAL FINDINGS: Using the national surveillance data of human and livestock anthrax from 2005 to 2013, we conducted a retrospective epidemiological study and risk assessment of anthrax in mainland China. The potential determinants for the temporal and spatial distributions of human anthrax were also explored. We found that the majority of human anthrax cases were located in six provinces in western and northeastern China, and five clustering areas with higher incidences were identified. The disease mostly peaked in July or August, and males aged 30-49 years had higher incidence than other subgroups. Monthly incidence of human anthrax was positively correlated with monthly average temperature, relative humidity and monthly accumulative rainfall with lags of 0-2 months. A boosted regression trees (BRT) model at the county level reveals that densities of cattle, sheep and human, coverage of meadow, coverage of typical grassland, elevation, coverage of topsoil with pH > 6.1, concentration of organic carbon in topsoil, and the meteorological factors have contributed substantially to the spatial distribution of the disease. The model-predicted probability of occurrence of human cases in mainland China was mapped at the county level.
CONCLUSIONS/SIGNIFICANCE: Anthrax in China was characterized by significant seasonality and spatial clustering. The spatial distribution of human anthrax was largely driven by livestock husbandry, human density, land cover, elevation, topsoil features and climate. Enhanced surveillance and intervention for livestock and human anthrax in the high-risk regions, particularly on the Qinghai-Tibetan Plateau, is the key to the prevention of human infections.

PMID 27097318
M N Swartz
Recognition and management of anthrax--an update.
N Engl J Med. 2001 Nov 29;345(22):1621-6. doi: 10.1056/NEJMra012892. Epub 2001 Nov 6.
Abstract/Text
PMID 11704686
F A Abramova, L M Grinberg, O V Yampolskaya, D H Walker
Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979.
Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2291-4.
Abstract/Text A large epidemic of anthrax that occurred in Sverdlovsk (now Ekaterinburg), Russia, in 1979 resulted in the deaths of many persons. A series of 42 necropsies, representing a majority of the fatalities from this outbreak, consistently revealed pathologic lesions diagnostic of inhalational anthrax, namely hemorrhagic necrosis of the thoracic lymph nodes in the lymphatic drainage of the lungs and hemorrhagic mediastinitis. Bacillus anthracis was recovered in bacterial cultures of 20 cases, and organisms were detected microscopically in the infected tissues of nearly all of the cases. A novel observation was primary focal hemorrhagic necrotizing pneumonia at the apparent portal of entry in 11 cases. Mesenteric lymphadenitis occurred in only 9 cases. This remarkably large series demonstrated the full range of effects of anthrax bacteremia and toxemia (edema especially adjacent to sites of extensive infection and pleural effusions) and hematogenously disseminated infection [hemorrhagic meningitis (21 cases) and multiple gastrointestinal submucosal hemorrhagic lesions (39 cases)].

PMID 8460135
Hiroshi Takahashi, Paul Keim, Arnold F Kaufmann, Christine Keys, Kimothy L Smith, Kiyosu Taniguchi, Sakae Inouye, Takeshi Kurata
Bacillus anthracis incident, Kameido, Tokyo, 1993.
Emerg Infect Dis. 2004 Jan;10(1):117-20. doi: 10.3201/eid1001.030238.
Abstract/Text
PMID 15112666
Eric Jacob Stern, Kristin Broome Uhde, Sean Vincent Shadomy, Nancy Messonnier
Conference report on public health and clinical guidelines for anthrax.
Emerg Infect Dis. 2008 Apr;14(4). doi: 10.3201/eid1404.070969.
Abstract/Text On March 13-14, 2006, a meeting on anthrax, sponsored by the Centers for Disease Control and Prevention (CDC) in collaboration with the Southeastern Center for Emerging Biologic Threats, was held at Emory University in Atlanta, Georgia, USA. The meeting's agenda included discussion of postexposure prophylaxis (PEP), screening and evaluation, and treatment of the various manifestations of human anthrax. The goal was to convene subject matter experts for a review of research developments and clinical experience with anthrax prophylaxis and treatment and to make consensus recommendations for updating guidelines for PEP, treatment, and clinical evaluation of patients with anthrax. A 2001 conference on guidelines for anthrax has previously been summarized in this journal. This article summarizes the meeting's presentations and discussion. Consensus recommendations are summarized in the Table. Updated CDC guidelines for treatment and prophylaxis of anthrax will be published in detail in other CDC publications and are available on CDC's website at http://www.bt.cdc.gov/agent/anthrax/index.asp.

PMID 18394267
Nicholas E Kman, Richard N Nelson
Infectious agents of bioterrorism: a review for emergency physicians.
Emerg Med Clin North Am. 2008 May;26(2):517-47, x-xi. doi: 10.1016/j.emc.2008.01.006.
Abstract/Text The terrorist attacks on the United States in 2001 and the anthrax release soon after brought the issue of bioterrorism to the forefront in the medical community. Bioterrorism is the use of a biologic weapon to create terror and panic. Biologic weapons, or bioweapons, can be bacteria, fungi, viruses, or biologic toxins. Because the emergency department represents the front line of defense for the recognition of agents of bioterrorism, it is essential that emergency physicians have the ability to quickly diagnose victims of bioterrorism. This review examines the most deadly and virulent category A agents of bioterrorism, that is, anthrax, smallpox, plague, botulism, hemorrhagic fever viruses, and tularemia. The focus is on epidemiology, transmission, clinical manifestations, diagnosis, and treatment.

PMID 18406986
Jon-Erik C Holty, Dena M Bravata, Hau Liu, Richard A Olshen, Kathryn M McDonald, Douglas K Owens
Systematic review: a century of inhalational anthrax cases from 1900 to 2005.
Ann Intern Med. 2006 Feb 21;144(4):270-80.
Abstract/Text BACKGROUND: Mortality from inhalational anthrax during the 2001 U.S. attack was substantially lower than that reported historically.
PURPOSE: To systematically review all published inhalational anthrax case reports to evaluate the predictors of disease progression and mortality.
DATA SOURCES: MEDLINE (1966-2005), 14 selected journal indexes (1900-1966), and bibliographies of all retrieved articles.
STUDY SELECTION: Case reports (in any language) between 1900 and 2005 that met predefined criteria.
DATA EXTRACTION: Two authors (1 author for non-English-language reports) independently abstracted patient data.
DATA SYNTHESIS: The authors found 106 reports of 82 cases of inhalational anthrax. Mortality was statistically significantly lower for patients receiving antibiotics or anthrax antiserum during the prodromal phase of disease, multidrug antibiotic regimens, or pleural fluid drainage. Patients in the 2001 U.S. attack were less likely to die than historical anthrax case-patients (45% vs. 92%; P < 0.001) and were more likely to receive antibiotics during the prodromal phase (64% vs. 13%; P < 0.001), multidrug regimens (91% vs. 50%; P = 0.027), or pleural fluid drainage (73% vs. 11%; P < 0.001). Patients who progressed to the fulminant phase had a mortality rate of 97% (regardless of the treatment they received), and all patients with anthrax meningoencephalitis died.
LIMITATIONS: This was a retrospective case review of previously published heterogeneous reports.
CONCLUSIONS: Despite advances in supportive care, fulminant-phase inhalational anthrax is usually fatal. Initiation of antibiotic or anthrax antiserum therapy during the prodromal phase is associated with markedly improved survival, although other aspects of care, differences in clinical circumstances, or unreported factors may contribute to this observed reduction in mortality. Efforts to improve early diagnosis and timely initiation of appropriate antibiotics are critical to reducing mortality.

PMID 16490913
Katherine A Hendricks, Mary E Wright, Sean V Shadomy, John S Bradley, Meredith G Morrow, Andy T Pavia, Ethan Rubinstein, Jon-Erik C Holty, Nancy E Messonnier, Theresa L Smith, Nicki Pesik, Tracee A Treadwell, William A Bower, Workgroup on Anthrax Clinical Guidelines
Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults.
Emerg Infect Dis. 2014 Feb;20(2). doi: 10.3201/eid2002.130687.
Abstract/Text The Centers for Disease Control and Prevention convened panels of anthrax experts to review and update guidelines for anthrax postexposure prophylaxis and treatment. The panels included civilian and military anthrax experts and clinicians with experience treating anthrax patients. Specialties represented included internal medicine, pediatrics, obstetrics, infectious disease, emergency medicine, critical care, pulmonology, hematology, and nephrology. Panelists discussed recent patients with systemic anthrax; reviews of published, unpublished, and proprietary data regarding antimicrobial drugs and anthrax antitoxins; and critical care measures of potential benefit to patients with anthrax. This article updates antimicrobial postexposure prophylaxis and antimicrobial and antitoxin treatment options and describes potentially beneficial critical care measures for persons with anthrax, including clinical procedures for infected nonpregnant adults. Changes from previous guidelines include an expanded discussion of critical care and clinical procedures and additional antimicrobial choices, including preferred antimicrobial drug treatment for possible anthrax meningitis.

PMID 24447897
Charles E Binkley, Sandro Cinti, Diane M Simeone, Lisa M Colletti
Bacillus anthracis as an agent of bioterrorism: a review emphasizing surgical treatment.
Ann Surg. 2002 Jul;236(1):9-16.
Abstract/Text OBJECTIVE: To familiarize surgeons with the specific complications of cutaneous, gastrointestinal, inhalation, and systemic infection with Bacillus Anthracis, which may require surgical treatment.
SUMMARY BACKGROUND DATA: The recent cases of intentional exposure to Bacillus Anthracis in the United States make familiarity with the basic microbiology, clinical manifestations, diagnosis, treatment, and control of this disease essential if mortality and morbidity is to be minimized, particularly following mass exposure. Although the treatment of Bacillus Anthracis infection is primarily medical, there are specific surgical complications with which the surgeon should be familiar.
METHODS: A review of the literature was undertaken, utilizing electronic databases on infection with Bacillus Anthracis, as well as consultation with experts in this field. Emphasis was placed on the diagnosis and treatment of complications of infection that might require surgical intervention.
RESULTS: Cutaneous anthrax infection results in eschar formation and massive soft tissue edema. When involving the extremities, increased compartment pressure requiring fasciotomy may result. Primary infection of the gastrointestinal tract may result in oropharyngeal edema and respiratory compromise requiring a surgical airway. Direct involvement of the lower gastrointestinal tract can result in intestinal ulceration, necrosis, bleeding, and perforation, which would require surgical exploration and resection of affected segments. Systemic sepsis, most often associated with inhalation anthrax, can cause massive ascites, electrolyte derangements, and profound shock requiring aggressive fluid resuscitation and careful hemodynamic monitoring and respiratory support. Systemic anthrax infection can also lead to gastrointestinal involvement by hematogenous dissemination, resulting in complications and requiring surgical management similar to direct gastrointestinal infection.
CONCLUSIONS: Cutaneous, gastrointestinal, inhalation and systemic infection with Bacillus Anthracis can result in complications which would require familiarity with the pathogenesis and manifestations of this disease in order to recognize and treat promptly and successfully by surgical intervention.

PMID 12131080
Satish K Pillai, Eileen Huang, Julie T Guarnizo, Jamechia D Hoyle, Stefan Katharios-Lanwermeyer, Theresa K Turski, William A Bower, Katherine A Hendricks, Dana Meaney-Delman
Antimicrobial Treatment for Systemic Anthrax: Analysis of Cases from 1945 to 2014 Identified Through a Systematic Literature Review.
Health Secur. 2015 Nov-Dec;13(6):355-64. doi: 10.1089/hs.2015.0033. Epub 2015 Dec 1.
Abstract/Text Systemic anthrax is associated with high mortality. Current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of 2 weeks, bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax, and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. However, in an anthrax mass casualty incident, large numbers of anthrax cases may create challenges in meeting antimicrobial needs. To further inform our understanding of the role of antimicrobials in treating systemic anthrax, a systematic review of the English-language literature was conducted to identify cases of systemic anthrax treated with antimicrobials for which a clinical outcome was recorded. A total of 149 cases of systemic anthrax were identified. Among the identified 59 cases of cutaneous anthrax, 33 were complicated by meningitis (76% mortality), while 26 simply had evidence of the systemic inflammatory response syndrome (4% mortality); 21 of 26 (81%) of this latter group received monotherapy. Subsequent analysis regarding combination antimicrobial therapy was restricted to the remaining 123 cases of more severe anthrax (overall 67% mortality). Recipients of combination bactericidal and protein synthesis inhibitor therapy had a 45% survival versus 28% in the absence of combination therapy (p = 0.07). For meningitis cases (n = 77), survival was greater for those receiving 3 or more antimicrobials over the course of treatment (3 of 4; 75%), compared to receipt of 1 or 2 antimicrobials (12 of 73; 16%) (p = 0.02). Median parenteral antimicrobial duration was 14 days. Combination bactericidal and protein synthesis inhibitor therapy may be appropriate in severe anthrax disease, particularly anthrax meningitis, in a mass casualty incident.

PMID 26623698
Vladimir Savransky, Boris Ionin, Joshua Reece
Current Status and Trends in Prophylaxis and Management of Anthrax Disease.
Pathogens. 2020 May 12;9(5). doi: 10.3390/pathogens9050370. Epub 2020 May 12.
Abstract/Text Bacillusanthracis has been identified as a potential military and bioterror agent as it is relatively simple to produce, with spores that are highly resilient to degradation in the environment and easily dispersed. These characteristics are important in describing how anthrax could be used as a weapon, but they are also important in understanding and determining appropriate prevention and treatment of anthrax disease. Today, anthrax disease is primarily enzootic and found mostly in the developing world, where it is still associated with considerable mortality and morbidity in humans and livestock. This review article describes the spectrum of disease caused by anthrax and the various prevention and treatment options. Specifically we discuss the following; (1) clinical manifestations of anthrax disease (cutaneous, gastrointestinal, inhalational and intravenous-associated); (2) immunology of the disease; (3) an overview of animal models used in research; (4) the current World Health Organization and U.S. Government guidelines for investigation, management, and prophylaxis; (5) unique regulatory approaches to licensure and approval of anthrax medical countermeasures; (6) the history of vaccination and pre-exposure prophylaxis; (7) post-exposure prophylaxis and disease management; (8) treatment of symptomatic disease through the use of antibiotics and hyperimmune or monoclonal antibody-based antitoxin therapies; and (9) the current landscape of next-generation product candidates under development.

PMID 32408493
Caitlin W Hicks, Daniel A Sweeney, Xizhong Cui, Yan Li, Peter Q Eichacker
An overview of anthrax infection including the recently identified form of disease in injection drug users.
Intensive Care Med. 2012 Jul;38(7):1092-104. doi: 10.1007/s00134-012-2541-0. Epub 2012 Apr 24.
Abstract/Text PURPOSE: Bacillus anthracis infection (anthrax) can be highly lethal. Two recent outbreaks related to contaminated mail in the USA and heroin in the UK and Europe and its potential as a bioterrorist weapon have greatly increased concerns over anthrax in the developed world.
METHODS: This review summarizes the microbiology, pathogenesis, diagnosis, and management of anthrax.
RESULTS AND CONCLUSIONS: Anthrax, a gram-positive bacterium, has typically been associated with three forms of infection: cutaneous, gastrointestinal, and inhalational. However, the anthrax outbreak among injection drug users has emphasized the importance of what is now considered a fourth disease form (i.e., injectional anthrax) that is characterized by severe soft tissue infection. While cutaneous anthrax is most common, its early stages are distinct and prompt appropriate treatment commonly produces a good outcome. However, early symptoms with the other three disease forms can be nonspecific and mistaken for less lethal conditions. As a result, patients with gastrointestinal, inhalational, or injectional anthrax may have advanced infection at presentation that can be highly lethal. Once anthrax is suspected, the diagnosis can usually be made with gram stain and culture from blood or tissue followed by confirmatory testing (e.g., PCR). While antibiotics are the mainstay of anthrax treatment, use of adjunctive therapies such as anthrax toxin antagonists are a consideration. Prompt surgical therapy appears to be important for successful management of injectional anthrax.

PMID 22527064
James J Walsh, Nicki Pesik, Conrad P Quinn, Veronica Urdaneta, Clare A Dykewicz, Anne E Boyer, Jeannette Guarner, Patricia Wilkins, Kim J Norville, John R Barr, Sherif R Zaki, Jean B Patel, Sarah P Reagan, James L Pirkle, Tracee A Treadwell, Nancy Rosenstein Messonnier, Lisa D Rotz, Richard F Meyer, David S Stephens
A case of naturally acquired inhalation anthrax: clinical care and analyses of anti-protective antigen immunoglobulin G and lethal factor.
Clin Infect Dis. 2007 Apr 1;44(7):968-71. doi: 10.1086/512372. Epub 2007 Feb 26.
Abstract/Text This report describes the first case of naturally acquired inhalation anthrax in the United States since 1976. The patient's clinical course included adjunctive treatment with human anthrax immunoglobulin. Clinical correlation of serologic assays for the lethal factor component of lethal toxin and anti-protective antigen immunoglobulin G are also presented.

PMID 17342650
A M Friedlander, S L Welkos, M L Pitt, J W Ezzell, P L Worsham, K J Rose, B E Ivins, J R Lowe, G B Howe, P Mikesell
Postexposure prophylaxis against experimental inhalation anthrax.
J Infect Dis. 1993 May;167(5):1239-43.
Abstract/Text Inhalation anthrax is a rare disease that is almost invariably fatal. This study determined whether a prolonged course of postexposure antibiotics with or without vaccination would protect monkeys exposed to a lethal aerosol dose of Bacillus anthracis when the antibiotic was discontinued. Beginning 1 day after exposure, groups of 10 animals were given penicillin, ciprofloxacin, doxycycline, doxycycline plus vaccination, vaccination alone, or saline. Antibiotics were administered for 30 days and then discontinued. Vaccine was given on days 1 and 15. Two animals died of causes other than anthrax and were not included in the statistical analysis. Nine of 10 controls and 8 of 10 animals given only vaccine died. Each antibiotic regimen completely protected animals while on therapy and provided significant long-term protection upon discontinuance of the drug (penicillin, 7 of 10 survived, P < .02; ciprofloxacin, 8 of 9 survived, P < .002; doxycycline, 9 of 10 survived, P < .002; doxycycline plus vaccination, 9 of 9 survived, P < .0002). Protection against rechallenge was provided by combining postexposure antibiotic treatment with vaccination.

PMID 8486963
William A Bower, Jarad Schiffer, Robert L Atmar, Wendy A Keitel, Arthur M Friedlander, Lindy Liu, Yon Yu, David S Stephens, Conrad P Quinn, Katherine Hendricks, ACIP Anthrax Vaccine Work Group
Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2019.
MMWR Recomm Rep. 2019 Dec 13;68(4):1-14. doi: 10.15585/mmwr.rr6804a1. Epub 2019 Dec 13.
Abstract/Text This report updates the 2009 recommendations from the CDC Advisory Committee on Immunization Practices (ACIP) regarding use of anthrax vaccine in the United States (Wright JG, Quinn CP, Shadomy S, Messonnier N. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP)], 2009. MMWR Recomm Rep 2010;59[No. RR-6]). The report 1) summarizes data on estimated efficacy in humans using a correlates of protection model and safety data published since the last ACIP review, 2) provides updated guidance for use of anthrax vaccine adsorbed (AVA) for preexposure prophylaxis (PrEP) and in conjunction with antimicrobials for postexposure prophylaxis (PEP), 3) provides updated guidance regarding PrEP vaccination of emergency and other responders, 4) summarizes the available data on an investigational anthrax vaccine (AV7909), and 5) discusses the use of anthrax antitoxins for PEP. Changes from previous guidance in this report include the following: 1) a booster dose of AVA for PrEP can be given every 3 years instead of annually to persons not at high risk for exposure to Bacillus anthracis who have previously received the initial AVA 3-dose priming and 2-dose booster series and want to maintain protection; 2) during a large-scale emergency response, AVA for PEP can be administered using an intramuscular route if the subcutaneous route of administration poses significant materiel, personnel, or clinical challenges that might delay or preclude vaccination; 3) recommendations on dose-sparing AVA PEP regimens if the anthrax vaccine supply is insufficient to vaccinate all potentially exposed persons; and 4) clarification on the duration of antimicrobial therapy when used in conjunction with vaccine for PEP.These updated recommendations can be used by health care providers and guide emergency preparedness officials and planners who are developing plans to provide anthrax vaccine, including preparations for a wide-area aerosol release of B. anthracis spores. The recommendations also provide guidance on dose-sparing options, if needed, to extend the supply of vaccine to increase the number of persons receiving PEP in a mass casualty event.

PMID 31834290
James J Sejvar, Fred C Tenover, David S Stephens
Management of anthrax meningitis.
Lancet Infect Dis. 2005 May;5(5):287-95. doi: 10.1016/S1473-3099(05)70113-4.
Abstract/Text Meningitis due to infection with Bacillus anthracis is considered an infrequent manifestation of the disease but one associated with high mortality. The bioterrorism event in the USA in the autumn of 2001 demonstrated our need for a better understanding of anthrax meningitis, as well as management and antimicrobial therapy. However, human clinical trials are not possible and animal experiments to guide such therapy are limited. An approach to the treatment of anthrax meningitis, based on the pathogenicity of B anthracis, the pharmacokinetics and pharmacodynamics of individual antimicrobial agents, studies of anthrax post-exposure prophylaxis in non-human primates, experience with antimicrobial susceptibility patterns of the 2001 outbreak strain, and the clinical experience with inhalational anthrax cases during the 2001 outbreak is presented. These outbreak data, the failure of previous single-drug regimens, the concerns of resistance, and the need for coverage for other causes of bacterial mengingitis suggest initial treatment of suspected anthrax meningitis should anchor on an intravenous fluoroquinolone and should include one or two other agents with activity against B anthracis and good penetration into the central nervous system. Such other agents include penicillin, ampicillin, meropenem, vancomycin, and rifampicin.

PMID 15854884

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