Bacillus anthracis: Difference between revisions

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{{Taxobox
{{Taxobox
| color = lightgrey
| name = ''Bacillus anthracis''
| name = ''Bacillus anthracis''
| image = Bacillus_anthracis_01.png
| image = Bacillus_anthracis.png
| image_width = 240px
| image_width = 240px
| image_caption = Photomicrograph of ''Bacillus anthracis'' (fuchsin-methylene blue spore stain).
| image_caption = Photomicrograph of ''Bacillus anthracis'' (fuchsin-methylene blue spore stain)
| regnum = [[Bacterium|Bacteria]]
| domain = [[Bacterium|Bacteria]]
| kingdom = [[Archaebacteria]]
| phylum = [[Firmicutes]]
| phylum = [[Firmicutes]]
| classis = [[Bacilli]]
| classis = [[Bacilli]]
Line 15: Line 15:
| binomial_authority = Cohn 1872
| binomial_authority = Cohn 1872
}}
}}
[[Image:B_anthracis_diagram_en.png|right|thumb|240px|Structure of ''Bacillus anthracis''.]]
__NOTOC__
__NOTOC__
{{CMG}}; {{AE}} {{JH}}
{{About0|Anthrax}}
 
{{Anthrax}}
{{CMG}}
==Overview==
==Overview==
'''''Bacillus anthracis''''' is a [[Gram-positive]], [[Facultative anaerobic organism|facultatively anaerobic]], rod-shaped [[bacterium]] of the genus ''[[Bacillus]]''. An [[endospore]] forming bacterium, ''B. anthracis'' is a natural soil-dwelling organism, as well as the causative agent of [[anthrax disease|anthrax]].<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | isbn = 0-8385-8529-9 }}</ref>
The causative agent of [[anthrax]] is [[B. anthracis]], a [[motility|nonmotile]], [[Gram-positive]], [[aerobic]] or facultatively [[anaerobic]], [[endospore]]-forming, [[rod]]-shaped [[bacterium]]. The [[spores]] of [[B. anthracis]], which can remain dormant in the environment for decades, are the [[infectious]] form, but this vegetative [[B. anthracis]] rarely causes disease.<ref>{{Cite journal | author = [[Sean V. Shadomy]] & [[Theresa L. Smith]] | title = Zoonosis update. Anthrax | journal = [[Journal of the American Veterinary Medical Association]] | volume = 233 | issue = 1 | pages = 63–72 | year = 2008 | month = July | doi = 10.2460/javma.233.1.63 | pmid = 18593313}}</ref> The [[Bacillus]] may enter the body through the [[skin]], [[lungs]], [[gastrointestinal system]] or by injection, after which they will travel to the [[lymph nodes]]. The [[virulence factor]]s will facilitate the translocation of the [[toxins]] to the [[cytosol]]. The [[natural reservoir]]s of [[Bacillus anthracis]] include humans, mammals, herbivores, reptiles, and birds.
 
Each cell is about 1 by 6 [[micrometre|μm]] in size.
 
==Historical background==
''B. anthracis'' was the first bacterium conclusively demonstrated to cause disease, by [[Robert Koch]] in 1877.<ref name=Brock>{{cite book | author = Madigan M, Martinko J (editors). | title = Brock Biology of Microorganisms | edition = 11th ed. | publisher = Prentice Hall | year = 2005 | isbn = 0-13-144329-1 }}</ref> The species name ''anthracis'' is from the [[Greek language|Greek]] ''anthrakis'' (ἄνθραξ), meaning ''coal'' and referring to the most common form of the disease, [[cutaneous]] anthrax, in which large black skin [[lesion]]s are formed.
 
==Pathogenicity==
Under conditions of environmental stress, ''B. anthracis'' bacteria naturally produce endospores which rest in the soil and can survive for decades in this state.  When ingested by a cattle, sheep, or other [[herbivore]]s, the bacteria begin to reproduce inside the animal and eventually kill it, then continue to reproduce in its carcass.  Once the nutrients are exhausted, new endospores are produced and the cycle repeats.<ref name=Baron>{{cite book | author = Turnbull PCB | title = Bacillus. ''In:'' Barron's Medical Microbiology ''(Baron S ''et al'', eds.)| edition = 4th ed. | publisher = Univ of Texas Medical Branch | year = 1996 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.925 | isbn = 0-9631172-1-1}}</ref>
 
''B. anthracis'' has at least 89 known [[strain (biology)|strains]], ranging from highly virulent strains with [[biological warfare]] and [[bioterrorism]] applications ([[Ames strain|Ames]] and ''Vollum'') to benign strains used for [[inoculation]]s (''Sterne''). The strains differ in presence and activity of various [[gene]]s, determining their [[virulence]] and production of [[antigen]]s and [[toxin]]s. The form associated with the [[2001 anthrax attacks]] produced both [[anthrax toxin|toxin]] (consisting of three [[protein]]s: [[anthrax toxin|the protective antigen, the edema factor and the lethal factor]]) and a [[Capsule_(microbiology)|capsule]] (consisting of a polymer of glutamic acid).  Infection with anthrax requires the presence of all three of these exotoxins.<ref>{{cite journal |author=Dixon TC, Meselson M, Guillemin J, Hanna PC |title=Anthrax |journal=N. Engl. J. Med. |volume=341 |issue=11 |pages=815-26 |year=1999 |pmid=10477781 |doi=}}</ref>
 
The bacterium can be cultivated in ordinary nutrient medium under aerobic or anaerobic conditions.
 
==Treatment==
{{main|Anthrax}}
Infections with ''B. anthracis'' can be treated with [[Beta-lactam|β-lactam]] [[antibiotic]]s such as [[penicillin]], and others which are active against Gram-positive bacteria.<ref>{{cite journal |author = Barnes JM |title=Penicillin and ''B. anthracis''. |journal= J Path Bacteriol |volume=194|year=1947|pages=113}}</ref>
 
==Treatment==
 
===Antimicrobial therapy===
 
:*  '''Bacillus anthracis treatment'''
 
::* 1. '''Treatment for cutaneous anthrax, without systemic involvement'''<ref name="pmid24447897">{{cite journal| author=Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT et al.| title=Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. | journal=Emerg Infect Dis | year= 2014 | volume= 20 | issue= 2 | pages=  | pmid=24447897 | doi=10.3201/eid2002.130687 | pmc=PMC3901462 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24447897  }} </ref>
 
:::* Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (1): [[Ciprofloxacin]] 500 mg PO bid for 7-10 days
 
:::* Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (2): [[Doxycycline]] 100 mg PO bid for 7-10 days
 
:::* Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (3): [[Levofloxacin]] 750 mg PO qd for 7-10 days
 
:::* Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (4): [[Moxifloxacin]] 400 mg PO qd for 7-10 days
 
:::* Alternative regimen (1): [[Clindamycin]] 600 mg PO tid for 7-10 days
 
:::* Alternative regimen (2): [[Amoxicillin]] 1 g PO tid (for penicillin-susceptible strains) for 7-10 days
 
:::* Alternative regimen (3): [[Penicillin VK]] 500 mg PO qid (for penicillin-susceptible strains) for 7-10 days
 
:::* Note: Duration of treatment is 60 days for bioterrorism-related cases and 7-10 days for naturally acquired cases.
 
::* 2. '''Treatment for systemic anthrax including anthrax meningitis, inhalational anthrax, injectional anthrax, and gastrointestinal anthrax; and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck'''<ref name="pmid24447897">{{cite journal| author=Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT et al.| title=Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. | journal=Emerg Infect Dis | year= 2014 | volume= 20 | issue= 2 | pages=  | pmid=24447897 | doi=10.3201/eid2002.130687 | pmc=PMC3901462 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24447897  }} </ref>
 
:::* 2.1 '''Systemic anthrax with possible/confirmed meningitis'''
 
::::* 2.1.1 '''Bactericidal agent''' (fluoroquinolone)
 
:::::* Preferred regimen (1): '''[[Ciprofloxacin]] 400 mg IV q8h''' for 2-3 weeks
 
:::::* Preferred regimen (2): [[Levofloxacin]] 750 mg IV q24h for 2-3 weeks
 
:::::* Preferred regimen (3): [[Moxifloxacin]] 400 mg IV q24h for 2-3 weeks {{and}}
 
::::* 2.1.2 '''Bactericidal agent (ß-lactam) for all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
 
:::::* Preferred regimen (1): '''[[Meropenem]] 2 g IV q8h''' for 2-3 weeks
 
:::::* Preferred regimen (2): [[Imipenem]] 1 g IV q6h for 2-3 weeks
 
:::::* Preferred regimen (3): [[Doripenem]] 500 mg IV q8h for 2-3 weeks
 
:::::* Preferred regimen (4): [[Penicillin G]] 4 MU IV q4h (for penicillin-susceptible strains) for 2-3 weeks
 
:::::* Preferred regimen (5): [[Ampicillin]] 3 g IV q6h (for penicillin-susceptible strains) for 2-3 weeks {{and}}
 
::::* 2.1.3 '''Protein synthesis inhibitor'''
 
:::::* Preferred regimen (1): '''[[Linezolid]] 600 mg IV q12h''' for 2-3 weeks
 
:::::* Preferred regimen (2): [[Clindamycin]] 900 mg IV q8h for 2-3 weeks
 
:::::* Preferred regimen (3): [[Rifampin]] 600 mg IV q12h for 2-3 weeks
 
:::::* Preferred regimen (4): [[Chloramphenicol]] 1 g IV q6-8h for 2-3 weeks
 
:::::* Note (1): Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.
 
:::::* Note (2): Increased risk for seizures associated with [[Imipenem]]/[[Cilastatin]] treatment.
 
:::::* Note (3): [[Linezolid]] should be used with caution in patients with thrombocytopenia because it might exacerbate it. [[Linezolid]] use for > 14 days has additional hematopoietic toxicity.
 
:::::* Note (4): [[Rifampin]] is not a protein synthesis inhibitor. However, it may be used in combination with other antimicrobial drugs on the basis of its in vitro synergy.
 
:::* 2.2 '''Systemic anthrax when meningitis has been excluded'''
 
::::* 2.2.1 '''Bactericidal agent'''
 
:::::* Preferred regimen (1): '''[[Ciprofloxacin]] 400 mg IV q8h'''for 2 weeks
 
:::::* Preferred regimen (2): [[Levofloxacin]] 750 mg IV q24h for 2 weeks
 
:::::* Preferred regimen (3): [[Moxifloxacin]] 400 mg q24h for 2 weeks
 
:::::* Preferred regimen (4): [[Meropenem]] 2 g IV q8h for 2 weeks
 
:::::* Preferred regimen (5): [[Imipenem]] 1 g IV q6h for 2 weeks
 
:::::* Preferred regimen (6): [[Doripenem]] 500 mg IV q8h for 2 weeks
 
:::::* Preferred regimen (7): [[Vancomycin]] 20 mg/kg IV q8h (maintain serum trough concentrations of 15-20 µg/mL) for 2 weeks
 
:::::* Preferred regimen (8): [[Penicillin G]] 4 MU IV q4h (penicillin-susceptible strains) for 2 weeks
 
:::::* Preferred regimen (9): [[Ampicillin]] 3 g IV q6h (penicillin-susceptible strains) for 2 weeks {{and}}
 
::::* 2.2.2 '''Protein synthesis inhibitor'''
 
:::::* Preferred regimen (1): '''[[Clindamycin]] 900 mg IV q8h''' for 2 weeks
 
:::::* Preferred regimen (2): '''[[Linezolid]] 600 mg IV q12h''' for 2 weeks
 
:::::* Preferred regimen (3): [[Doxycycline]] 200 mg IV initially, then 100 mg IV q12h for 2 weeks
 
:::::* Preferred regimen (4): [[Rifampin]] 600 mg IV q12h for 2 weeks
 
:::::* Note: Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.
 
::* 3. '''Specific considerations'''
 
:::* 3.1 '''Treatment of anthrax for pregnant Women'''
 
::::* 3.1.1 '''Intravenous antimicrobial treatment for systemic anthrax with possible/confirmed meningitis''' <ref name="pmid24457117">{{cite journal| author=Meaney-Delman D, Zotti ME, Creanga AA, Misegades LK, Wako E, Treadwell TA et al.| title=Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women. | journal=Emerg Infect Dis | year= 2014 | volume= 20 | issue= 2 | pages=  | pmid=24457117 | doi=10.3201/eid2002.130611 | pmc=PMC3901460 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24457117  }} </ref>
 
:::::* 3.1.1.1 ''' A bactericidal agent (fluoroquinolone)'''
 
::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 400 mg IV q8h for 2–3 weeks
 
::::::* Preferred regimen (2): [[Levofloxacin]] 750 mg IV q24h for 2–3 weeks{{or}}
 
:::::* 3.1.1.2 ''' A bactericidal agent (ß-lactam)'''
 
::::::* 3.1.1.2.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
 
:::::::* Preferred regimen: '''[[Meropenem]] 2 g q8h''' for 2–3 weeks
 
::::::* 3.1.1.2.2 '''Alternatives for penicillin-susceptible strains'''
 
:::::::* Alternative regimen (1): [[Ampicillin]] 3 g IV q6h for 2–3 weeks
 
:::::::* Alternative regimen (2): [[Penicillin G]] 4 MU IV q4h for 2–3 weeks {{or}}
 
:::::* 3.1.1.3 ''' A protein synthesis Inhibitor'''
 
::::::* Preferred regimen (1): '''[[Clindamycin]] 900 IV mg q8h''' for 2–3 weeks
 
::::::* Preferred regimen (2): [[Rifampin]] 600 IV mg q12h for 2–3 weeks
 
::::::* Note: At least one antibiotic with transplacental passage is recommended.
 
::::* 3.1.2 '''Intravenous antimicrobial treatment for systemic anthrax when meningitis has been excluded'''
 
:::::* 3.1.2.1 ''' A bactericidal Antimicrobial'''
 
::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 400 mg IV q8h''' for 2 weeks
 
::::::* Preferred regimen (2): [[Levofloxacin]] 750 mg IV q24h for 2 weeks {{or}}
 
:::::* 3.1.2.2 ''' A bactericidal Agent (ß-lactam)'''
 
::::::* 3.1.2.2.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
 
:::::::* Preferred regimen: '''[[Meropenem]] 2 g q8h''' for 2 weeks  {{or}}
 
::::::* 3.1.2.2.2 '''Alternatives for penicillin-susceptible strains'''
 
:::::::* Alternative regimen (1): [[Ampicillin]] 3 g IV q6h for 2 weeks
 
:::::::* Alternative regimen (2): [[Penicillin G]] 4 MU IV q4h for 2 weeks {{or}}
 
:::::* 3.1.2.3 ''' A protein synthesis inhibitor'''
 
::::::* Preferred regimen (1): [[Clindamycin]] 900 IV mg q8h for 2 weeks
 
::::::* Preferred regimen (2): [[Rifampin]] 600 IV mg q12h for 2 weeks
 
::::* 3.1.3 '''Oral antimicrobial treatment for cutaneous anthrax without systemic involvement'''
 
:::::* 3.1.3.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
 
::::::* Preferred regimen: '''[[Ciprofloxacin]] 400 mg IV q8h'''
 
::::::* Note: Duration of treatment is 60 days
 
:::* 3.2 '''Treatment for anthrax in childern''' <ref name="pmid24777226">{{cite journal| author=Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney-Delman D et al.| title=Pediatric anthrax clinical management. | journal=Pediatrics | year= 2014 | volume= 133 | issue= 5 | pages= e1411-36 | pmid=24777226 | doi=10.1542/peds.2014-0563 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24777226  }} </ref>
 
::::* 3.2.1 '''Treatment of cutaneous anthrax without systemic involvement (for children 1 month of age and older)'''
 
:::::* 3.2.1.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
 
::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 30 mg/kg/day PO bid (not to exceed 500 mg/dose)''' for 7-10 days
 
::::::* Preferred regimen (2):
 
:::::::* If patients body weight is < 45 kg: [[Doxycycline]] 4.4 mg/kg/day PO bid (not to exceed  100 mg/dose) for 7-10 days
 
:::::::* If patients body weight is = 45 kg: [[Doxycycline]]  100 mg/dose PO bid for 7-10 days
 
::::::* Preferred regimen (3): [[Clindamycin]] 30 mg/kg/day PO tid (not to exceed  600 mg/dose) for 7-10 days
 
::::::* Preferred regimen (4):
 
:::::::* If patients body weight is < 50 kg: [[Levofloxacin]] 16 mg/kg/day PO bid (not to exceed  250 mg/dose) for 7-10 days
 
:::::::* If patients body weight is > 50 kg: [[Levofloxacin]] 500 mg PO qd for 7-10 days
 
:::::* 3.2.1.2 '''Alternatives for penicillin-susceptible strains'''
 
::::::* Alternative regimen (1):'''[[Amoxicillin]] 75 mg/kg/day PO tid (not to exceed 1 g/dose)''' for 7-10 days
 
::::::* Alternative regimen (2): [[Penicillin VK]] 50-75 mg/kg/day PO tid or qid for 7-10 days
 
::::* 3.2.2 ''' Combination therapy for systemic anthrax when meningitis can be ruled out (for children 1 month of age and older)'''
 
:::::* 3.2.2.1 '''A bactericidal antimicrobial'''
 
::::::* 3.2.2.1.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
 
:::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 30 mg/kg/day IV divided q8h (not to exceed 400 mg/dose)''' for 14 days
 
:::::::* Preferred regimen (2): [[Meropenem]] 60 mg/kg/day IV divided q8h (not to exceed 2 g/dose) for 14 days
 
:::::::* Preferred regimen (3):
 
::::::::* If patients body weight is < 50 kg: [[Levofloxacin]] 20 mg/kg/day IV divided q12h (not to exceed 250 mg/dose) for 14 days
 
::::::::* If patients body weight is > 50 kg: [[Levofloxacin]] 500 mg IV q24h for 14 days
 
:::::::* Preferred regimen (4): [[Imipenem]]/[[Cilastatin]] 100 mg/kg/day IV divided q6h (not to exceed 1 g/dose) for 14 days
 
:::::::* Preferred regimen (5): [[Vancomycin]] 60 mg/kg/day IV divided q8h (follow serum concentrations) for 14 days
 
::::::* 3.2.2.1.2 '''Alternatives for penicillin-susceptible strains'''
 
:::::::* Alternative regimen (1): '''[[Penicillin G]] 400 000 U/kg/day IV divided q4h (not to exceed 4 MU/dose)''' for 14 days
 
:::::::* Alternative regimen (2): [[Ampicillin]] 200 mg/kg/day IV divided q6h (not to exceed 3 g/dose) for 14 days {{and}}
 
:::::* 3.2.2.2 '''A protein synthesis inhibitor'''
 
::::::* Preferred regimen (1): '''[[Clindamycin]], 40 mg/kg/day IV divided q8h (not to exceed 900 mg/dose)''' for 14 days
 
::::::* Preferred regimen (2):  (non-CNS infection dose)
 
:::::::* If patient is < 12 y old: [[Linezolid]] 30 mg/kg/day IV divided q8h for 14 days
 
:::::::* If patient is = 12 y old: [[Linezolid]] 30 mg/kg/day IV divided q12h (not to exceed 600 mg/dose) for 14 days
 
::::::* Preferred regimen (3):
 
:::::::* If patients body weight is < 45 kg: [[Doxycycline]] 4.4 mg/kg/day IV loading dose (not to exceed 200 mg) {{then}} [[Doxycycline]] 4.4 mg/kg/day IV divided q12h  (not to exceed 100 mg/dose) for 14 days
 
:::::::* If patients body weight is =45 kg: [[Doxycycline]] 200 mg IV loading dose {{then}} [[Doxycycline]] 100 mg IV given q12h for 14 days
 
::::::* Preferred regimen (4): [[Rifampin]] 20 mg/kg/day IV divided q12h (not to exceed 300 mg/dose) for 14 days
 
::::::* Note: Duration of therapy for 14 days or longer until clinical criteria for stability are met.Will require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
 
::::* 3.2.3 '''Triple therapy for systemic anthrax (anthrax meningitis or disseminated infection and meningitis cannot be ruled out) for Children 1 Month of Age and Older'''
 
:::::* 3.2.3.1 '''A bactericidal antimicrobial''' (fluoroquinolone)
 
::::::* Preferred regimen (1): [[Ciprofloxacin]] 30 mg/kg/day IV divided q8h (not to exceed 400 mg/dose) for 2–3 wks
 
::::::* Preferred regimen (2):
 
:::::::* If patients body weight is < 50 kg: [[Levofloxacin]] 16 mg/kg/day IV divided q12h (not to exceed 250 mg/dose) for 2–3 wks
 
:::::::* If patients body weight is > 50 kg: [[Levofloxacin]] 500 mg IV q24h for 2–3 wks
 
::::::* Preferred regimen (3):
 
:::::::* If patients age is 3 months to < 2 years: [[Moxifloxacin]]  12 mg/kg/day IV, divided q12h (not to exceed 200 mg/dose) for 2–3 wks
 
:::::::* If patients age is 2-5 years: [[Moxifloxacin]] 10 mg/kg/day IV divided q1h (not to exceed 200 mg/dose) for 2–3 wks
 
:::::::* If patients age is 6–11 years: [[Moxifloxacin]] 8 mg/kg/day IV divided q12h (not to exceed 200 mg/dose) for 2–3 wks
 
:::::::* If patients age is 12–17 years, = 45 kg body weight: [[Moxifloxacin]] 400 mg IV q24h for 2–3 wks
 
:::::::* If patients age is 12–17 years, < 45 kg body weight: [[Moxifloxacin]] 8 mg/kg/day IV divided q12h (not to exceed 200 mg/dose) for 2–3 wks {{and}}
 
:::::* 3.2.3.2 '''A bactericidal antimicrobial (ß-lactam or glycopeptide)'''
 
::::::* 3.2.3.2.1 '''For all strains, regardless of penicillin susceptibility testing or if susceptibility is unknown''':
 
:::::::* Preferred regimen (1): [[Meropenem]] 120 mg/kg/day IV divided q8h (not to exceed 2 g/dose) for 2–3 wks
 
:::::::* Preferred regimen (2): [[Imipenem]]/[[Cilastatin]] 100 mg/kg/day IV divided q6h (not to exceed 1 g/dose) for 2–3 wks
 
:::::::* Preferred regimen (3): [[Doripenem]] 120 mg/kg/day IV divided q8h (not to exceed 1 g/dose) for 2–3 wks
 
:::::::* Preferred regimen (4): [[Vancomycin]] 60 mg/kg/day IV divided q8h for 2–3 wks
 
::::::* 3.2.3.2.2 '''Alternatives for penicillin-susceptible strains'''
 
:::::::* Alternative regimen (1): [[Penicillin G]] 400 000 U/kg/day IV divided q4h (not to exceed 4 MU/dose) for 2–3 wks
 
:::::::* Alternative regimen (2): [[Ampicillin]] 400 mg/kg/day IV divided q6h (not to exceed 3 g/dose) for 2–3 wks {{and}}
 
::::::* 3.2.3.3 '''A protein synthesis inhibitor'''
 
:::::::* Preferred regimen (1):
 
::::::::* If patients age is < 12 y old: [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 wk
 
::::::::* If patients age is = 12 y old: [[Linezolid]] 30 mg/kg/day,IV divided q12h (not to exceed 600 mg/dose) for 2–3 wk
 
:::::::* Preferred regimen (2): [[Clindamycin]] 40 mg/kg/day IV divided q8h (not to exceed 900 mg/dose)  for 2–3 wk
 
:::::::* Preferred regimen (3): [[Rifampin]] 20 mg/kg/day IV divided q12h (not to exceed 300 mg/dose) for 2–3 wk
 
:::::::* Preferred regimen (4): [[Chloramphenicol]] 100 mg/kg/day IV divided q6h for 2–3 wk
 
:::::::* Note (1): Duration of therapy for 2–3 wk or greater, until clinical criteria for stability are met.Will require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
 
:::::::* Note (2):  A 400-mg dose of [[Ciprofloxacin]] IV, provides an equivalent exposure to that of a 500-mg ciprofloxacin oral tablet.
 
::::* 3.2.4 '''Oral follow-up combination therapy for severe anthrax (for Children 1 Month of Age and Older)'''
 
:::::* 3.2.4.1 '''A bactericidal antimicrobial'''
 
::::::* 3.2.4.1.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
 
:::::::* Preferred regimen (1): [[Ciprofloxacin]] 30 mg/kg/day PO bid (not to exceed 500 mg/dose)
 
:::::::* Preferred regimen (2):
 
::::::::* If patients body weight is < 50 kg: [[Levofloxacin]] 16 mg/kg/day PO bid (not to exceed 250 mg/dose)
 
::::::::* If patients body weight is = 50 kg: [[Levofloxacin]] 500 mg PO qd
 
::::::* 3.2.4.1.2 '''Alternatives for penicillin-susceptible strains'''
 
:::::::* Alternative regimen (1): [[Amoxicillin]] 75 mg/kg/day PO tid (not to exceed 1 g/dose)
 
:::::::* Alternative regimen (2): [[Penicillin VK]] 50–75 mg/kg/day PO tid or qds {{and}}
 
:::::* 3.2.4.2 '''A protein synthesis inhibitor''':
 
::::::* Preferred regimen (1):[[Clindamycin]] 30 mg/kg/day PO tid (not to exceed 600 mg/dose)
 
::::::* Preferred regimen (2):
 
:::::::* If the patients body weight is < 45 kg: [[Doxycycline]] 4.4 mg/kg/day PO bid (not exceed 100 mg/dose)
 
:::::::* If the patients body weight is = 45 kg: [[Doxycycline]] 100 mg PO bid
 
::::::* Preferred regimen (3): (non-CNS infection dose):
 
:::::::* If the patients age is < 12 yrs old: [[Linezolid]] 30 mg/kg/day PO tid
 
:::::::* If the patients age is = 12 yrs old: [[Linezolid]] 30 mg/kg/day PO bid (not to exceed 600 mg/dose)
 
:::::::* Note: Duration of therapy to complete a treatment course of 14 days or greater. May require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
 
::::* 3.2.5 ''' Dosing in preterm and term neonates 32 to 44 Weeks postmenstrual Age (Gestational Age Plus Chronologic Age)'''
 
:::::* 3.2.5.1 '''Triple therapy for severe anthrax(anthrax meningitis or disseminated infection and meningitis cannot be ruled out)'''
 
::::::* 3.2.5.1.1 '''Bactericidal antimicrobial (fluoroquinolone) therapy'''
 
:::::::*  3.2.5.1.1.1 '''For 32–34 weeks gestational age '''
 
::::::::* '''For 0–1 week of age'''
 
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 20 mg/kg/day IV divided q12h''' for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Moxifloxacin]] 5 mg/kg/day IV q24h for 2–3 weeks
 
::::::::* '''For 1–4 weeks of age'''
 
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 20 mg/kg/day IV divided q12h''' for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Moxifloxacin]] 5 mg/kg/day IV q24h for 2–3 weeks
 
:::::::*  3.2.5.1.1.2 '''For 34–37 week gestational age '''
 
::::::::* '''For 0–1 wk of age'''
 
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 20 mg/kg/day IV divided q12h''' for 2–3 weeks
 
:::::::::* Preferred regimen (2):[[Moxifloxacin]] 5 mg/kg/day IV q24h for 2–3 weeks
 
::::::::* '''For 1–4 wk of age'''
 
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 20 mg/kg/day IV divided q12h''' for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Moxifloxacin]] 5 mg/kg/day IV q24h for 2–3 weeks
 
:::::::*  3.2.5.1.1.3 '''Term newborn infant'''
 
::::::::* '''For 0–1 week of age'''
 
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 30 mg/kg/day IV divided q12h''' for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Moxifloxacin]] 10 mg/kg/day IV q24h for 2–3 weeks
 
::::::::* '''For 1–4 weeks of age'''
 
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 30 mg/kg/day IV divided q12h''' for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Moxifloxacin]] 10 mg/kg/day IV q24h for 2–3 weeks {{and}}
 
::::::* 3.2.5.1.2 '''A bactericidal antimicrobial (ß-lactam)'''
 
:::::::* 3.2.5.1.2.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown''':
 
::::::::* 3.2.5.1.2.1.1 '''For 32–34 weeks gestational age'''
 
:::::::::* For 0–1 week of Age :
 
::::::::::* Preferred regimen (1): '''[[Meropenem]]''' 60 mg/kg/day  IV divided q8h for 2–3 weeks
 
::::::::::* Preferred regimen (2): [[Imipenem]] 50 mg/kg/day  IV divided q12h for 2–3 weeks
 
::::::::::* Preferred regimen (3): [[Doripenem]] 20 mg/kg/day  IV divided q12h for 2–3 weeks
 
:::::::::* For 1–4 wk of Age :
 
::::::::::* Preferred regimen (1): '''[[Meropenem]]''' 90 mg/kg/day  IV divided q8h for 2–3 weeks
 
::::::::::* Preferred regimen (2): [[Imipenem]] 75 mg/kg/day  IV divided q8h for 2–3 weeks
 
::::::::::* Preferred regimen (3): [[Doripenem]] 30 mg/kg/day  IV divided q8h for 2–3 weeks
 
::::::::* 3.2.5.1.2.1.2 '''For 34–37 week gestational age'''
 
:::::::::* For 0–1 week of Age :
 
::::::::::* Preferred regimen (1): '''[[Meropenem]]''' 60 mg/kg/day IV divided q8h for 2–3 weeks
 
::::::::::* Preferred regimen (2): [[Imipenem]] 50 mg/kg/day IV divided q12h for 2–3 weeks
 
::::::::::* Preferred regimen (3): [[Doripenem]]  20 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* For 1–4 week of Age :
 
::::::::::* Preferred regimen (1): '''[[Meropenem]]''' 90 mg/kg/day IV divided q8h for 2–3 weeks
 
::::::::::* Preferred regimen (2): [[Imipenem]] 75 mg/kg/day IV divided q8h for 2–3 weeks
 
::::::::::* Preferred regimen (3): [[Doripenem]] 30 mg/kg/day IV divided q8h for 2–3 weeks
 
::::::::* 3.2.5.1.2.1.3 '''Term newborn infant'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Preferred regimen (1):'''[[Meropenem]]''' 60 mg/kg/day IV divided q8h for 2–3 weeks
 
::::::::::* Preferred regimen (2): [[Imipenem]] 50 mg/kg/day IV divided q12h for 2–3 weeks
 
::::::::::* Preferred regimen (3): [[Doripenem]] 20 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Preferred regimen (1):'''[[Meropenem]]''' 90 mg/kg/day IV divided q8h for 2–3 weeks
 
::::::::::* Preferred regimen (2): [[Imipenem]] 75 mg/kg/day IV divided q8h for 2–3 weeks
 
::::::::::* Preferred regimen (3): [[Doripenem]] 30 mg/kg/day IV divided q8h for 2–3 weeks
 
:::::::* 3.2.5.1.2.2 ''' Alternatives for penicillin-susceptible strains'''
 
::::::::* 3.2.5.1.2.2.1 '''For 32–34 weeks gestational age'''
 
:::::::::* '''For 0–1 week of age'''
 
::::::::::* Alternative regimen (1):'''[[Penicillin G]]''' 200000 Units/kg/day IV divided q12h for 2–3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 100 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* '''For 1–4 week of age''' :
 
::::::::::* Alternative regimen (1): '''[[Penicillin G]]''' 300000 Units/kg/day IV divided q12h for 2–3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 150 mg/kg/day divided IV q12h for 2–3 weeks
 
::::::::* 3.2.5.1.2.2.2 '''For 34–37 week gestational age'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Alternative regimen (1): '''[[Penicillin G]]''' 300000 Units/kg/day IV divided q12h for 2–3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 150 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Alternative regimen (1): '''[[Penicillin G]]''' 400000 Units/kg/day IV divided q12h for 2–3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 200 mg/kg/day IV divided q12h for 2–3 weeks
 
::::::::* 3.2.5.1.2.2.3 '''Term newborn infant'''
 
:::::::::* '''For 0–1 week of age'''
 
::::::::::* Alternative regimen (1): '''[[Penicillin G]]''' 300000 Units/kg/day IV divided q12h for 2–3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 150 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Alternative regimen (1): '''[[Penicillin G]]''' 400000 Units/kg/day IV divided q12h for 2–3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 200 mg/kg/day IV divided q12h for 2–3 weeks {{and}}
 
::::::* 3.2.5.1.3 '''A protein synthesis inhibitor'''
 
:::::::* 3.2.5.1.3.1 '''For 32–34 weeks gestational age'''
 
::::::::* '''For < 1 week of age'''
 
:::::::::* Preferred regimen (1): '''[[Linezolid]]''' 20 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Clindamycin]] 10 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* Preferred regimen (4): [[Chloramphenicol]] 25 mg/kg/day IV q24h for 2–3 weeks
 
::::::::* '''For 1–4 week of age'''
 
:::::::::* Preferred regimen (1): '''[[Linezolid]]''' 30 mg/kg/day IV divided q8h for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Clindamycin]] 15 mg/kg/day IV divided q8h for 2–3 weeks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* Preferred regimen (4): [[Chloramphenicol]] 50 mg/kg/day IV q12h for 2–3 weeks
 
:::::::* 3.2.5.1.3.2 '''For 34–37 week gestational age'''
 
::::::::* '''For < 1 week of age'''
 
:::::::::* Preferred regimen (1): '''[[Linezolid]]''' 30 mg/kg/day IV divided q8h for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Clindamycin]] 15 mg/kg/day IV divided q8h for 2–3 weeks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* Preferred regimen (4): [[Chloramphenicol]] 25 mg/kg/day IV q24h for 2–3 weeks
 
::::::::* '''For 1–4 week of age'''
 
:::::::::* Preferred regimen (1):'''[[Linezolid]]''' 30 mg/kg/day IV divided q8h for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Clindamycin]] 20 mg/kg/day IV divided q6h for 2–3 weeks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* Preferred regimen (4): [[Chloramphenicol]] 50 mg/kg/day IV q12h for 2–3 weeks
 
:::::::* 3.2.5.1.3.3 '''Term newborn infant'''
 
::::::::* '''For < 1 week of age'''
 
:::::::::* Preferred regimen (1):'''[[Linezolid]]''' 30 mg/kg/day IV divided q8h for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Clindamycin]] 15 mg/kg/day IV divided q8h for 2–3 weeks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* Preferred regimen (4): [[Chloramphenicol]] 25 mg/kg/day IV q24h for 2–3 weeks
 
::::::::* '''For 1–4 week of age'''
 
:::::::::* Preferred regimen (1): '''[[Linezolid]]''' 30 mg/kg/day IV divided q8h for 2–3 weeks
 
:::::::::* Preferred regimen (2): [[Clindamycin]] 20 mg/kg/day IV divided q6h for 2–3 weeks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 20 mg/kg/day IV divided q12h for 2–3 weeks
 
:::::::::* Preferred regimen (4): [[Chloramphenicol]] 50 mg/kg/day IV q12h for 2–3 weeks
 
:::::::::* Note :Duration of therapy for 2–3 weeks, until clinical criteria for stability are met. Will require prophylaxis to complete an antibiotic course of upto 60 days from onset of illness.
 
:::::* 3.2.5.2 '''Therapy for severe anthrax when meningitis can be ruled out'''
 
::::::* 3.2.5.2.1 '''A bactericidal antimicrobial'''
 
:::::::* 3.2.5.2.1.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
 
::::::::* 3.2.5.2.1.1.1 '''For 32–34 weeks gestational age'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 20 mg/kg/day IV divided q12h''' for 2-3 weeks
 
::::::::::* Preferred regimen (2): [[Meropenem]] 40 mg/kg/day IV divided q8h for 2-3 weeks
 
::::::::::* Preferred regimen (3): [[Imipenem]] 40 mg/kg/day IV divided q12h for 2-3 weeks
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 20 mg/kg/day IV divided q12h''' for 2-3 weeks
 
::::::::::* Preferred regimen (2): [[Meropenem]] 60 mg/kg/day IV divided q8h for 2-3 weeks
 
::::::::::* Preferred regimen (3): [[Imipenem]] 50 mg/kg/day IV divided q12h for 2-3 weeks
 
::::::::* 3.2.5.2.1.1.2 '''For 34–37 week gestational age'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 20 mg/kg/day IV divided q12h''' for 2-3 weeks
 
::::::::::* Preferred regimen (2): [[Meropenem]] 60 mg/kg/day IV divided q8h for 2-3 weeks
 
::::::::::* Preferred regimen (3): [[Imipenem]] 50 mg/kg/day IV divided q12h for 2-3 weeks
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 20 mg/kg/day IV divided q12h''' for 2-3 weeks
 
::::::::::* Preferred regimen (2): [[Meropenem]] 60 mg/kg/day IV divided q8h for 2-3 weeks
 
::::::::::* Preferred regimen (3): [[Imipenem]] 75 mg/kg/day IV divided q8h for 2-3 weeks
 
::::::::* 3.2.5.2.1.1.3 '''Term newborn infant'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Preferred regimen (1): '''[[Ciprofloxacin]] 30 mg/kg/day IV divided q12h''' for 2-3 weeks
 
::::::::::* Preferred regimen (2): [[Meropenem]] 60 mg/kg/day IV divided q8h for 2-3 weeks
 
::::::::::* Preferred regimen (3): [[Imipenem]] 50 mg/kg/day IV divided q12h for 2-3 weeks
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Preferred regimen (1):'''[[Ciprofloxacin]] 30 mg/kg/day IV divided q12h''' for 2-3 weeks
 
::::::::::* Preferred regimen (2): [[Meropenem]] 60 mg/kg/day IV divided q8h for 2-3 weeks
 
::::::::::* Preferred regimen (3): [[Imipenem]] 75 mg/kg/day IV divided q8h for 2-3 weeks
 
:::::::::::* [[Vancomycin]] IV (dosing based on serum creatinine for infants of 32 wk gestational age). Follow vancomycin serum concentrations to modify dose.
 
::::::::::::* If  Serum creatinine < 0.7 then [[Vancomycin]] 15 mg/kg/dose IV q12h for 2-3 weeks
 
::::::::::::* If Serum creatinine 0.7 -0.9 then [[Vancomycin]] 20 mg/kg/dose IV q24h for 2-3 weeks
 
::::::::::::* If Serum creatinine 1–1.2 then [[Vancomycin]] 15 mg/kg/dose IV q24h for 2-3 weeks
 
::::::::::::* If Serum creatinine 1.3–1.6 then [[Vancomycin]] 10 mg/kg/dose IV q24h for 2-3 weeks
 
::::::::::::* If Serum creatinine > 1.6 then [[Vancomycin]] mg/kg/dose IV q48h for 2-3 weeks
 
::::::::::* Note: Begin treatment with a 20 mg/kg loading dose {{or}}
 
:::::::* 3.2.5.2.1.2 '''Alternatives for penicillin-susceptible strains'''
 
::::::::* 3.2.5.2.1.2.1 '''For 32–34 weeks gestational age'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Alternative regimen (1): [[Penicillin G]] 200000 U/kg/day IV divided q12h for 2-3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 100 mg/kg/day IV divided q12h for 2-3 weeks
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Alternative regimen (1): [[Penicillin G]] 300000 U/kg/day IV divided q8h for 2-3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 150 mg/kg/day IV divided q8h for 2-3 weeks
 
::::::::* 3.2.5.2.1.2.2 '''For 34–37 week gestational age'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Alternative regimen (1): [[Penicillin G]] 300000 U/kg/day IV divided q8h for 2-3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 150 mg/kg/day IV divided q8h for 2-3 weeks
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Alternative regimen (1): [[Penicillin G]] 400000 U/kg/day IV divided q6h for 2-3 weeks
::::::::::* Alternative regimen (2): [[Ampicillin]] 200 mg/kg/day IV divided q6h for 2-3 weeks
 
::::::::* 3.2.5.2.1.2.3 '''Term newborn infant'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Alternative regimen (1): [[Penicillin G]] 300000 U/kg/day IV divided q8h for 2-3 weeks
 
::::::::::* Alternative regimen (2): [[Ampicillin]] 150 mg/kg/day IV divided q8h for 2-3 weeks
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Alternative regimen (1): [[Penicillin G]] 400000 U/kg/day IV divided q6h for 2-3 weeks
 
::::::::::* Alternative regimen (2):[[Ampicillin]] 200 mg/kg/day IV divided q6h for 2-3 weeks
 
::::::* 3.2.5.2.2 '''A protein synthesis inhibitor'''
 
:::::::* 3.2.5.2.2.1 '''For 32–34 weeks gestational age'''
 
::::::::* '''For < 1 week of age'''
 
:::::::::* Preferred regimen (1): [[Clindamycin]] 10 mg/kg/day IV divided q12h for 2–3 wks
 
:::::::::* Preferred regimen (2): [[Linezolid]] 20 mg/kg/day IV divided q12h for 2–3 wks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 wks
 
::::::::* '''For 1–4 week of age'''
 
:::::::::* Preferred regimen (1): [[Clindamycin]] 15 mg/kg/day IV divided q8h for 2–3 wks
 
:::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 wks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 wks
 
:::::::* 3.2.5.2.2.2 '''For 34–37 week gestational age'''
 
::::::::* '''For < 1 week of age'''
 
:::::::::* Preferred regimen (1): [[Clindamycin]]  15 mg/kg/day IV divided q8h for 2–3 wks
 
:::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 wks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 wks
 
::::::::* '''For 1–4 week of age'''
 
:::::::::* Preferred regimen (1): [[Clindamycin]] 20 mg/kg/day IV divided q6h for 2–3 wks
 
:::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 wks
 
:::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 wks
 
:::::::* 3.2.5.2.2.3 '''Term newborn infant'''
 
::::::::* For 0–1 week of age :
 
:::::::::* Preferred regimen (1): [[Clindamycin]] 15 mg/kg/day  IV divided q8h for 2–3 wks
 
:::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 wks
 
:::::::::* Preferred regimen (3): [[Doxycycline]] 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 wks
 
:::::::::* Preferred regimen (4): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 wks
 
::::::::* For 1–4 week of age :
 
:::::::::* Preferred regimen (1): [[Clindamycin]] 20 mg/kg/day IV divided q6h for 2–3 wks
 
:::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 wks
 
:::::::::* Preferred regimen (3): [[Doxycycline]] 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 wks
 
:::::::::* Preferred regimen (4): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 wks
 
:::::::::* Note: Duration of therapy for 2–3 wks, until clinical criteria for stability are met (see text). Will require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness
 
:::::* 3.2.5.3 '''Oral follow-up combination therapy for severe anthrax'''
 
::::::* 3.2.5.3.1 '''A bactericidal antimicrobial'''
 
:::::::* 3.2.5.3.1.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
 
::::::::* 3.2.5.3.1.1.1 '''For 32–34 weeks gestational age'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Preferred regimen: '''[[Ciprofloxacin]] 20 mg/kg/day PO bid'''
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Preferred regimen: '''[[Ciprofloxacin]] 20 mg/kg/day PO bid'''
 
::::::::* 3.2.5.3.1.1.2 '''For 34–37 week gestational age'''
 
:::::::::*  '''For < 1 week of age'''
 
::::::::::* Preferred regimen: '''[[Ciprofloxacin]] 20 mg/kg/day PO bid'''
 
:::::::::* '''For 1–4 week of age'''
 
::::::::::* Preferred regimen: '''[[Ciprofloxacin]] 20 mg/kg/day PO bid'''
 
::::::::* 3.2.5.3.1.1.3 '''Term newborn infant'''
 
:::::::::* '''For < 1 week of age'''
 
::::::::::* Preferred regimen: '''[[Ciprofloxacin]] 30 mg/kg/day PO bid'''


:::::::::* '''For 1–4 week of age'''
== Historical background ==
French physician [[Casimir Davaine]] (1812-1882) demonstrated the symptoms of anthrax were invariably accompanied by the microbe ''B. anthracis''.<ref>{{cite journal
|last=Théodoridès
|first=J
|authorlink=
|date=April 1966
|title=Casimir Davaine (1812-1882): a precursor of Pasteur
|journal=Medical history
|volume=10
|issue=2
|pages=155–65
| publisher = | pmid = 5325873
| bibcode = |pmc=1033586
| doi=10.1017/S0025727300010942
}}</ref>  German physician [[Aloys Pollender]] (1799–1879) is also credited for this discovery. ''B. anthracis'' was the first bacterium conclusively demonstrated to cause disease, by [[Robert Koch]] in 1876.<ref>Koch, R. (1876) "Untersuchungen über Bakterien: V. Die Ätiologie der Milzbrand-Krankheit, begründet auf die Entwicklungsgeschichte des ''Bacillus anthracis''" (Investigations into bacteria: V. The etiology of anthrax, based on the ontogenesis of ''Bacillus anthracis''), Cohns ''Beitrage zur Biologie der Pflanzen'', vol. 2, no. 2, [http://edoc.rki.de/documents/rk/508-5-26/PDF/5-26.pdf pages 277–310].</ref> The species name ''anthracis'' is from the [[Greek language|Greek]] ''anthrax''<!--[sic]--> (ἄνθραξ), meaning "coal" and referring to the most common form of the disease, [[cutaneous]] anthrax, in which large, black skin [[lesion]]s are formed.


::::::::::* Preferred regimen: '''[[Ciprofloxacin]] 30 mg/kg/day PO bid''' {{or}}
==Biology==
[[B. anthracis]], the causative agent of [[anthrax]], is a [[motility|nonmotile]], [[Gram-positive]], [[aerobic]] or facultatively [[anaerobic]], [[endospore]]-forming, [[rod]]-shaped [[bacterium]] approximately 4 μm by 1 μm, although under the microscope it frequently appears in chains of [[cells]]. Like other [[Bacillus]], [[Bacillus anthracis]] is  saprophyte, being able to live in vegetation, air, water and soil.<ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref>


:::::::* 3.2.5.3.1.2 '''Alternatives for penicillin-susceptible strains'''
These [[bacterial]] [[cells]] may occur isolated, form groups of 2 or more [[cells]] in the body, or long chains in [[cell culture|cultures]].<ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref> In [[blood smear]]s, smears of [[tissue]]s or lesion fluid from [[diagnostic]] specimens, these chains are two to a few [[cells]] in length. In smears made from [[in vitro]] cultures, they can appear as endless strings of [[cells]] - responsible for the characteristic tackiness of the colonies and for the flocculating nature of broth cultures. [[Cell culture]]s appear with a large, grey and curled structure, resembling a "medusa head".<ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref>


::::::::* 3.2.5.3.1.2.1 '''For 32–34 weeks gestational age'''
[[B. anthracis]] have a characteristic square-ended appearance, traditionally associated with its vegetative state, although this may not always be very clear. In the presence of [[oxygen]], ideally at 32 - 35 ºC, and towards the end of the exponential phase of growth, one ellipsoidal [[spore]] (approximately 2 μm by 1 μm in size) is formed within each [[cell]].<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref><ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref> Commonly the [[spores]] will be produced once the [[cell]] senses scarcity of [[nutrients]].<ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref>


:::::::::* '''For < 1 week of age'''
The [[spores]] of [[B. anthracis]], which can remain dormant in the environment for decades, being resistant to heat and disinfectants, are the [[infectious]] form, but vegetative [[B. anthracis]] rarely causes disease.<ref>{{Cite journal | author = [[Sean V. Shadomy]] & [[Theresa L. Smith]] | title = Zoonosis update. Anthrax | journal = [[Journal of the American Veterinary Medical Association]] | volume = 233 | issue = 1 | pages = 63–72 | year = 2008 | month = July | doi = 10.2460/javma.233.1.63 | pmid = 18593313}}</ref><ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref>


::::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 50 mg/kg/day PO bid
In the absence of [[oxygen]] and under a high partial pressure of Co2, in the presence of [[bicarbonate]], the vegetative [[cell]] secretes its [[polypeptide]] [[capsule]]. This is one of the two established [[in vivo]] [[virulence factor]]s of [[B. anthracis]]. The [[capsule]] is also a primary [[diagnostic]] aid.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref> Protective [[antigen]] (PA) and [[edema]] factor (EF) combine to form [[edema]] toxin (ET) and PA and lethal factor (LF) combine to form lethal toxin (LT), the active [[toxins]].<ref>{{Cite journal | author = [[Mahtab Moayeri]] & [[Stephen H. Leppla]] | title = The roles of anthrax toxin in pathogenesis | journal = [[Current opinion in microbiology]] | volume = 7 | issue = 1 | pages = 19–24 | year = 2004 | month = February | doi = 10.1016/j.mib.2003.12.001 | pmid = 15036135}}</ref><ref name=CDC>{{cite web | title = Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults | url = http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article }}</ref>


::::::::::* Alternative regimen (2): Penicillin VK  50 mg/kg/day PO bid


:::::::::* '''For 1–4 week of age'''
{| style="float: right;"
| [[File:AnthraxCauses2.png|200px|thumb|none| Photomicrograph depicting a number of Gram-positive, endospore-forming Bacillus anthracis bacteria<SMALL>Courtesy: ''[http://phil.cdc.gov/phil/home.asp Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|-
| [[File:AnthraxCauses1.jpg|200px|thumb|none| Scanning electron micrograph (SEM) depicted spores from the Sterne strain of Bacillus anthracis bacteria<SMALL>Courtesy: ''[http://phil.cdc.gov/phil/home.asp Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|}


::::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 75 mg/kg/day PO bid
==Genome structure==
''B. anthracis'' has a single chromosome which is a circular, 5,227,293-bp DNA molecule.<ref name="Read">{{cite journal|last=Read|first=TD|coauthors=Peterson, SN; Tourasse, N; Baillie, LW; Paulsen, IT; Nelson, KE; Tettelin, H; Fouts, DE; Eisen, JA; Gill, SR; Holtzapple, EK; Okstad, OA; Helgason, E; Rilstone, J; Wu, M; Kolonay, JF; Beanan, MJ; Dodson, RJ; Brinkac, LM; Gwinn, M; DeBoy, RT; Madpu, R; Daugherty, SC; Durkin, AS; Haft, DH; Nelson, WC; Peterson, JD; Pop, M; Khouri, HM; Radune, D; Benton, JL; Mahamoud, Y; Jiang, L; Hance, IR; Weidman, JF; Berry, KJ; Plaut, RD; Wolf, AM; Watkins, KL; Nierman, WC; Hazen, A; Cline, R; Redmond, C; Thwaite, JE; White, O; Salzberg, SL; Thomason, B; Friedlander, AM; Koehler, TM; Hanna, PC; Kolstø, AB; Fraser, CM|title=The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria.|journal=Nature|date=May 1, 2003|volume=423|issue=6935|pages=81–6|pmid=12721629|doi=10.1038/nature01586}}</ref>  It also has two circular, extrachromosomal, double-stranded DNA plasmids, pXO1 and pXO2. Both the pXO1 and pXO2 plasmids are required for full virulence and represent two distinct plasmid families.<ref name="Kolstø">{{cite journal|last=Kolstø|first=Anne-Brit|author2=Tourasse, Nicolas J.|author3= Økstad, Ole Andreas|title=What Sets                            Apart from Other                            Species?|journal=Annual Review of Microbiology|date=1 October 2009|volume=63|issue=1|pages=451–476|doi=10.1146/annurev.micro.091208.073255}}</ref>


::::::::::* Alternative  regimen (2): Penicillin VK 75 mg/kg/day PO bid
{| class="wikitable"
|-
! Feature !! scope="col" width="100px" | Chromosome !! scope="col" width="100px" | pXO1 !! scope="col" width="100px" | pXO2
|-
| Size (bp) || align="right"|5,227,293 || align="right"|181,677 || align="right"|94,829
|-
| Number of genes || align="right"|5,508 || align="right"|217 || align="right"|113
|-
| [[Replicon (genetics)|Replicon]] coding (%) || align="right"|84.3 || align="right"|77.1 || align="right"|76.2
|-
| Average [[gene]] length (nt) || align="right"|800 || align="right"|645 || align="right"|639
|-
| G+C content (%) || align="right"|35.4 || align="right"|32.5 || align="right"|33.0
|-
| [[rRNA]] operons || align="right"|11 || align="right"|0 || align="right"|0
|-
| [[tRNA]]s || align="right"|95 || align="right"|0 || align="right"|0
|-
| [[Small RNA|sRNAs]] || align="right"|3 || align="right"|2 || align="right"|0
|-
| [[Phage]] genes || align="right"|62 || align="right"|0 || align="right"|0
|-
| [[Transposon]] genes || align="right"|18 || align="right"|15 || align="right"|6
|-
| Disrupted reading frame || align="right"|37 || align="right"|5 || align="right"|7
|-
| Genes with assigned function || align="right"|2,762 || align="right"|65 || align="right"|38
|-
| Conserved hypothetical genes || align="right"|1,212 || align="right"|22 || align="right"|19
|-
| Genes of unknown function || align="right"|657 || align="right"|8 || align="right"|5
|-
| Hypothetical genes || align="right"|877 || align="right"|122 || align="right"|51
|}


::::::::* 3.2.5.3.1.2.2 '''For 34–37 week gestational age'''
===pXO1 plasmid===
The pXO1 plasmid (182 kb) contains the genes that encode for the [[anthrax toxin]] components: ''pag'' (protective antigen, PA), ''lef'' (lethal factor, LF), and ''cya'' (edema factor, EF).  These factors are contained within a 44.8-kb [[pathogenicity island]] (PAI).  The lethal toxin is a combination of PA with LF and the edema toxin is a combination of PA with EF.  The PAI also contains genes which encode a [[transcriptional activator]] AtxA and the [[repressor]] PagR, both of which regulate the expression of the anthrax toxin genes.<ref name="Kolstø" />


:::::::::* '''For < 1 week of age'''
===pXO2 plasmid===
pXO2 encodes a five-gene [[operon]] (''capBCADE'') which synthesizes a poly-γ-D-glutamic acid (polyglutamate) capsule.  This capsule allows ''B. anthracis'' to evade the host immune system by protecting itself from [[phagocytosis]].  Expression of the capsule operon is activated by the transcriptional regulators AcpA and AcpB, located in the pXO2 pathogenicity island (35 kb).  Interestingly, AcpA and AcpB expression are under the control of AtxA from pXO1.<ref name="Kolstø" />


::::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 50 mg/kg/day PO bid
==Strains==
The 89 known strains of ''B. anthracis'' include:
*[[Sterne strain]] (34F2; aka the "Weybridge strain"), used by [[Max Sterne]] in his 1930s vaccines
*[[Vollum strain]], formerly weaponized by the US, UK, and Iraq; isolated from cow in [[Oxfordshire]], UK, in 1935
**Vollum M-36, virulent British research strain; passed through macaques 36 times
**Vollum 1B, weaponized by the US and UK in the 1940s-60s
**Vollum-14578, UK biotesting contaminated [[Gruinard Island]], Scotland, in 1940s
**V770-NP1-R, the avirulent, nonencapsulated strain used in the ''[[BioThrax]]'' vaccine
*Anthrax 836, highly virulent strain weaponized by the USSR; discovered in [[Kirov, Kirov Oblast|Kirov]] in 1953
*[[Ames strain]], isolated from a cow in [[Texas]] in 1981; famously used in [[AMERITHRAX]] letter attacks (2001)
**Ames Ancestor
**Ames Florida
*H9401, isolated from human patient in Korea; used in investigational anthrax vaccines<ref name="Chun" />


::::::::::* Alternative regimen (2): Penicillin VK 50 mg/kg/day PO bid
==Evolution==
Whole genome sequencing has made reconstruction of the ''B. anthracis'' phylogeny extremely accurate.  A contributing factor to the reconstruction is ''B. anthracis'' being monomorphic, meaning it has low genetic diversity, including the absence of any measurable lateral DNA transfer since its derivation as a species.  The lack of diversity is due to a short evolutionary history that has precluded mutational saturation in [[single nucleotide polymorphisms]].<ref name="Keim">{{cite journal|last=Keim|first=Paul|author2=Gruendike, Jeffrey M.|author3= Klevytska, Alexandra M.|author4= Schupp, James M.|author5= Challacombe, Jean|author6= Okinaka, Richard|title=The genome and variation of Bacillus anthracis|journal=Molecular Aspects of Medicine|date=1 December 2009|volume=30|issue=6|pages=397–405|doi=10.1016/j.mam.2009.08.005|pmid=19729033|pmc=3034159}}</ref>


:::::::::* '''For 1–4 week of age'''
A short evolutionary time does not necessarily mean a short chronological time.  When DNA is replicated, mistakes occur which become genetic mutations.  The buildup of these mutations over time leads to the evolution of a species.  During the ''B. anthracis'' lifecycle, it spends a significant amount of time in the soil spore reservoir stage, a stage in which DNA replication does not occur.  These prolonged periods of dormancy have greatly reduced the evolutionary rate of the organism.<ref name="Keim" />


::::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 75 mg/kg/day PO bid
===Nearest neighbors===
''B. anthracis'' belongs to the ''B. cereus'' group consisting of the strains: ''B. cereus'', ''B. anthracis'', ''B. thuringiensis'', ''[[Bacillus weihenstephanensis|B. weihenstephanensis]]'', ''[[Bacillus mycoides|B. mycoides]]'', and ''B. pseudomycoides''.  The first three strains are pathogenic or opportunistic to insects or mammals, while the last three are not considered pathogenic.  The strains of this group are genetically and phenotypically heterogeneous overall, but some of the strains are more closely related and phylogenetically intermixed at the chromosome level.  The ''B. cereus'' group generally exhibits complex genomes and most carry varying numbers of plasmids.<ref name="Kolstø" />


::::::::::* Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid
''B. cereus'' is a soil-dwelling bacterium which can colonize the gut of invertebrates as a symbiont<ref>{{cite journal|last=Jensen|first=G. B.|author2=Hansen, B. M.|author3= Eilenberg, J.|author4= Mahillon, J.|title=The hidden lifestyles of Bacillus cereus and relatives|journal=Environmental Microbiology|date=18 July 2003|volume=5|issue=8|pages=631–640|doi=10.1046/j.1462-2920.2003.00461.x|pmid=12871230}}</ref>  and is a frequent cause of food poisoning<ref>{{cite journal|last=Drobniewski|first=FA|title=Bacillus cereus and related species.|journal=Clinical Microbiology Reviews|date=October 1993|volume=6|issue=4|pages=324–38|pmid=8269390|pmc=358292}}</ref>  It produces an emetic toxin, enterotoxins, and other virulence factors.<ref>{{cite journal|last=Stenfors Arnesen|first=Lotte P.|author2=Fagerlund, Annette|author3= Granum, Per Einar|title=From soil to gut:                           and its food poisoning toxins|journal=FEMS Microbiology Reviews|date=1 July 2008|volume=32|issue=4|pages=579–606|doi=10.1111/j.1574-6976.2008.00112.x|pmid=18422617}}</ref>    The enterotoxins and virulence factors are encoded on the chromosome, while the emetic toxin is encoded on a 270-kb plasmid, pCER270.<ref name="Kolstø" />


::::::::* 3.2.5.3.1.2.3 '''Term newborn infant'''
''B. thuringiensis'' is an insect pathogen and is characterized by production of parasporal crystals of insecticidal toxins Cry and Cyt.<ref>{{cite journal|last=Schnepf|first=E|author2=Crickmore, N|author3=Van Rie, J|author4=Lereclus, D|author5=Baum, J|author6=Feitelson, J|author7=Zeigler, DR|author8= Dean, DH|title=Bacillus thuringiensis and its pesticidal crystal proteins.|journal=Microbiology and molecular biology reviews : MMBR|date=September 1998|volume=62|issue=3|pages=775–806|pmid=9729609|pmc=98934}}</ref>    The genes encoding these proteins are commonly located on plasmids which can be lost from the organism, making it indistinguishable from ''B. cereus''.<ref name="Kolstø" />


:::::::::* '''For < 1 week of age'''  
===Pseudogene===
''PlcR'' is a global transcriptional regulator which controls most of the secreted virulence factors in ''B. cereus'' and ''B. thuringiensis''.  It is chromosomally encoded and is ubiquitous throughout the cell.<ref>{{cite journal|last=Agaisse|first=H|author2=Gominet, M|author3= Okstad, OA|author4= Kolstø, AB|author5= Lereclus, D|title=PlcR is a pleiotropic regulator of extracellular virulence factor gene expression in Bacillus thuringiensis.|journal=Molecular microbiology|date=June 1999|volume=32|issue=5|pages=1043–53|pmid=10361306|doi=10.1046/j.1365-2958.1999.01419.x}}</ref>    In ''B. anthracis'', however, the ''plcR'' gene contains a single base change at position 640, a nonsense mutation, which creates a dysfunctional protein.  While 1% of the ''B. cereus'' group carries an inactivated ''plcR'' gene, none of them carries the specific mutation found only in ''B. anthracis''.<ref>{{cite journal|last=Slamti|first=L|author2=Perchat, S|author3=Gominet, M|author4=Vilas-Bôas, G|author5=Fouet, A|author6=Mock, M|author7=Sanchis, V|author8=Chaufaux, J|author9=Gohar, M|author10= Lereclus, D|title=Distinct mutations in PlcR explain why some strains of the Bacillus cereus group are nonhemolytic.|journal=Journal of bacteriology|date=June 2004|volume=186|issue=11|pages=3531–8|pmid=15150241|doi=10.1128/JB.186.11.3531-3538.2004|pmc=415780}}</ref>


::::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 75 mg/kg/day PO tid
The ''plcR'' gene is part of a two-gene operon with ''papR''.<ref>{{cite journal|last=Okstad|first=OA|author2=Gominet, M|author3= Purnelle, B|author4= Rose, M|author5= Lereclus, D|author6= Kolstø, AB|title=Sequence analysis of three Bacillus cereus loci carrying PIcR-regulated genes encoding degradative enzymes and enterotoxin.|journal=Microbiology (Reading, England)|date=November 1999|volume=145|pages=3129–38|pmid=10589720|issue=11}}</ref><ref name="Slamti">{{cite journal|last=Slamti|first=L|author2=Lereclus, D|title=A cell-cell signaling peptide activates the PlcR virulence regulon in bacteria of the Bacillus cereus group.|journal=The EMBO Journal|date=Sep 2, 2002|volume=21|issue=17|pages=4550–9|pmid=12198157|pmc=126190|doi=10.1093/emboj/cdf450}}</ref>  The ''papR'' gene encodes a small protein which is secreted from the cell and the reimported as a processed heptapeptide forming a quorum-sensing system.<ref name="Slamti" /><ref>{{cite journal|last=Bouillaut|first=L|author2=Perchat, S|author3=Arold, S|author4=Zorrilla, S|author5=Slamti, L|author6=Henry, C|author7=Gohar, M|author8=Declerck, N|author9= Lereclus, D|title=Molecular basis for group-specific activation of the virulence regulator PlcR by PapR heptapeptides|journal=Nucleic Acids Research|date=June 2008|volume=36|issue=11|pages=3791–801|pmid=18492723|doi=10.1093/nar/gkn149|pmc=2441798}}</ref>  The lack of PlcR in ''B. anthracis'' is a principle characteristic differentiating it from other members of the ''B. cereus'' group.  While ''B. cereus'' and ''B. thuringiensis'' depend on the ''plcR'' gene for expression of their virulence factors, ''B. anthracis'' relies on the pXO1 and pXO2 plasmids for its virulence.<ref name="Kolstø" />


::::::::::* Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid
== Laboratory research ==
Components of [[tea]], such as [[polyphenols in tea|polyphenol]]s, have the ability to inhibit the activity both of ''B. anthracis'' and its toxin considerably; spores, however, are not affected. The addition of milk to the tea completely inhibits its antibacterial activity against anthrax.<ref>{{cite web|url = http://web.archive.org/web/20090213231226/http://www.sfam.org.uk/newsarticle.php?214&2 |title=Anthrax and tea|publisher = Society for Applied Microbiology |accessdate = 2011-12-21|date=2011-12-21}}</ref> Activity against the ''B. athracis'' in the [[laboratory]] does not prove that drinking tea affects the course of an infection, since it is unknown how these polyphenols are absorbed and distributed within the body.


:::::::::* '''For 1–4 week of age'''  
===Recent research===
Advances in genotyping methods have led to improved genetic analysis for variation and relatedness.  These methods include multiple-locus variable-number tandem repeat analysis ([[MLVA]]) and typing systems using canonical [[single-nucleotide polymorphisms]].  The Ames ancestor chromosome was sequenced in 2003<ref name="Read" /> and contributes to the identification of genes involved in the virulence of ''B. anthracis''.  Recently, ''B. anthracis'' isolate H9401 was isolated from a Korean patient suffering from gastrointestinal anthrax.  The goal of the Republic of Korea is to use this strain as a challenge strain to develop a recombinant vaccine against anthrax.<ref name="Chun">{{cite journal|last=Chun|first=J.-H.|author2=Hong, K.-J.|author3=Cha, S. H.|author4=Cho, M.-H.|author5=Lee, K. J.|author6=Jeong, D. H.|author7=Yoo, C.-K.|author8= Rhie, G.-e.|title=Complete Genome Sequence of Bacillus anthracis H9401, an Isolate from a Korean Patient with Anthrax|journal=Journal of Bacteriology|date=18 July 2012|volume=194|issue=15|pages=4116–4117|doi=10.1128/JB.00159-12|pmid=22815438|pmc=3416559}}</ref>


::::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 75 mg/kg/day PO tid
The H9401 strain isolated in the Republic of Korea was sequenced using [[454 Life Sciences|454]] GS-FLX technology and analyzed using several bioinformatics tools to align, annotate, and compare H9401 to other ''B. anthracis'' strains.  The sequencing coverage level suggests a molecular ratio of pXO1:pXO2:chromosome as 3:2:1 which is identical to the Ames Florida and Ames Ancestor strains.  H9401 has 99.679% sequence homology with Ames Ancestor with an [[amino acid]] sequence homology of 99.870%.  H9401 has a circular chromosome (5,218,947 bp with 5,480 predicted [[Open reading frame|ORF]]s), the pXO1 plasmid (181,700 bp with 202 predicted ORFs), and the pXO2 plasmid (94,824 bp with 110 predicted ORFs).<ref name="Chun" /> As compared to the Ames Ancestor chromosome above, the H9401 chromosome is about 8.5 kb smaller.  Due to the high pathogenecity and sequence similarity to the Ames Ancestor, H9401 will be used as a reference for testing the efficacy of candidate anthrax vaccines by the Repbulic of Korea.<ref name="Chun" />
::::::::::* Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid or qid


::::::* 3.2.5.3.2 '''A protein synthesis inhibitor'''
== Host interactions ==
As with most other pathogenic bacteria, ''B. anthracis'' must acquire iron to grow and proliferate in its host environment. The most readily available iron sources for pathogenic bacteria are the [[heme]] groups used by the host in the transport of oxygen. To scavenge heme from host [[hemoglobin]] and [[myoglobin]], ''B. anthracis'' uses two secretory [[siderophore]] proteins, IsdX1 and IsdX2. These proteins can separate heme from hemoglobin, allowing surface proteins of ''B. anthracis'' to transport it into the cell.<ref>{{cite journal |author = Maresso AW, Garufi G, Schneewind O |title=Bacillus anthracis Secretes Proteins That Mediate Heme Acquisition from Hemoglobin |journal= PLOS Pathogens |volume=4(8): e1000132|year=2008}}</ref>


:::::::* 3.2.5.3.2.1 '''For 32–34 weeks gestational age'''
==Origin==
[[Bacillus anthracis]] is thought to have originated in Egypt and Mesopotamia. Many scholars think that in Moses’ time, during the 10 plagues of Egypt, [[anthrax]] may have caused what was known as the fifth [[plague]], described as a sickness affecting horses, cattle, sheep, camels and oxen.


::::::::* '''For < 1 week of age'''
==Tropism==
:::::::::* Preferred regimen (1): '''[[Clindamycin]] 10 mg/kg/day PO bid'''
After entering the body (through the [[skin]], [[lungs]], [[gastrointestinal tract]] or by [[injection]]), [[B. anthracis]] [[spores]] are believed to germinate locally or be transported by [[phagocytic cells]] to the [[lymphatics]] and regional [[lymph nodes]], where they germinate.<ref name=CDC>{{cite web | title = Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults | url = http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article }}</ref><ref name="Ross1957">{{cite journal|last1=Ross|first1=Joan M.|title=The pathogenesis of anthrax following the administration of spores by the respiratory route|journal=The Journal of Pathology and Bacteriology|volume=73|issue=2|year=1957|pages=485–494|issn=0368-3494|doi=10.1002/path.1700730219}}</ref> After binding to [[cell]] surface receptors, the PA portion of the complexes facilitates translocation of the [[toxins]] to the [[cytosol]].<ref name="Moayeri2004">{{cite journal|last1=Moayeri|first1=M|title=The roles of anthrax toxin in pathogenesis|journal=Current Opinion in Microbiology|volume=7|issue=1|year=2004|pages=19–24|issn=13695274|doi=10.1016/j.mib.2003.12.001}}</ref><ref name=CDC>{{cite web | title = Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults | url = http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article }}</ref>


:::::::::* Preferred regimen (2): [[Linezolid]] 20 mg/kg/day PO bid
==Natural Reservoir==
[[Natural reservoir]]s of [[Bacillus anthracis]] include:<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref><ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref><ref name=CDC>{{cite web | title = Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults | url = http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article }}</ref>
* Humans
* Mammals
* Herbivores
* Reptiles
* Birds


::::::::* '''For 1–4 week of age'''
:::::::::* Preferred regimen (1): '''[[Clindamycin]] 15 mg/kg/day PO bid'''
:::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day PO bid
:::::::* 3.2.5.3.2.2 '''For 34–37 week gestational age'''
::::::::* '''For < 1 week of age'''
:::::::::* Preferred regimen (1): '''[[Clindamycin]] 15 mg/kg/day PO tid'''
:::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day PO tid
::::::::* '''For 1–4 week of age'''
:::::::::* Preferred regimen (1): '''[[Clindamycin]] 20 mg/kg/day PO qid'''
:::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day PO tid
:::::::* 3.2.5.3.2.3 '''Term newborn infant'''
::::::::* '''For < 1 week of age'''
:::::::::* Preferred regimen (1): '''[[Clindamycin]] 15 mg/kg/day PO tid'''
:::::::::* Preferred regimen (2): [[Doxycycline]] 4.4 mg/kg/day PO bid (loading dose 4.4 mg/kg) 
:::::::::* Preferred regimen (3): [[Linezolid]] 30 mg/kg/day PO tid
::::::::* '''For 1–4 week of age'''
:::::::::* Preferred regimen (1): '''[[Clindamycin]] 20 mg/kg/day PO qid'''
:::::::::* Preferred regimen (2): [[Doxycycline]] 4.4 mg/kg/day PO bid (loading dose 4.4 mg/kg)
:::::::::* Preferred regimen (3): [[Linezolid]] 30 mg/kg/day PO tid
:::::::::* Note: Duration of therapy to complete a treatment course of 10–14 days or greater. May require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness.
:::::* 3.2.5.4 '''Treatment of cutaneous anthrax without systemic involvement'''
::::::* 3.2.5.4.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
:::::::* 3.2.5.4.1.1 '''For 32–34 weeks gestational age'''
::::::::* '''For < 1 week of age'''
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 20 mg/kg/day PO bid
:::::::::* Preferred regimen (2): [[Clindamycin]] 10 mg/kg/day PO bid
::::::::* '''For 1–4 week of age'''
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 20 mg/kg/day PO bid
:::::::::* Preferred regimen (2): [[Clindamycin]] 15 mg/kg/day PO tid
:::::::* 3.2.5.4.1.2 '''For 34–37 week gestational age'''
::::::::* '''For < 1 week of age'''
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 20 mg/kg/day PO bid
:::::::::* Preferred regimen (2): [[Clindamycin]] 15 mg/kg/day PO tid
::::::::* '''For 1–4 week of age'''
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 20 mg/kg/day PO bid
:::::::::* Preferred regimen (2): [[Clindamycin]] 20 mg/kg/day PO qid
:::::::* 3.2.5.4.1.3 '''Term newborn infant'''
::::::::* '''For < 1 week of age'''
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 30 mg/kg/day PO bid
:::::::::* Preferred regimen (2): [[Doxycycline]] 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)
:::::::::* Preferred regimen (3): [[Clindamycin]] 15 mg/kg/day PO tid
::::::::* '''For 1–4 week of age'''
:::::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 30 mg/kg/day PO bid
:::::::::* Preferred regimen (2): [[Doxycycline]] 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)
:::::::::* Preferred regimen (3): [[Clindamycin]] 20 mg/kg/day PO qid
   
   
::::::* 3.2.5.4.2 '''Alternatives for penicillin-susceptible strains'''
:::::::* 3.2.5.4.2.1 '''For 32–34 weeks gestational age'''
::::::::* '''For < 1 week of age'''
:::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 50 mg/kg/day PO bid
:::::::::* Alternative regimen (2): Penicillin Vk 50 mg/kg/day PO bid
::::::::* '''For 1–4 week of age'''
:::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 75 mg/kg/day PO tid
:::::::::* Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid
:::::::* 3.2.5.4.2.2 '''For 34–37 week gestational age'''
::::::::* '''For < 1 week of age'''
:::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 50 mg/kg/day PO bid
:::::::::* Alternative regimen (2): Penicillin Vk 50 mg/kg/day PO bid
::::::::* '''For 1–4 week of age'''
:::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 75 mg/kg/day PO bid
:::::::::* Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO bid
:::::::* 3.2.5.4.2.3 '''Term newborn infant'''
::::::::* '''For < 1 week of age'''
:::::::::* Alternative regimen (1): '''[[Amoxicillin]]''' 75 mg/kg/day PO tid
:::::::::* Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid
::::::::* '''For 1–4 week of age'''
:::::::::* Alternative regimen (1): '''[[Amoxicillin]]'''  75 mg/kg/day PO tid
:::::::::* Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid or qid
:::::::::* Note : Duration of therapy for naturally acquired infection is 7–10 days and for a biological weapon–related event,may require additional prophylaxis for inhaled spores to complete an antimicrobial course of up to 60 days from onset of illness.
:* '''Bacillus anthracis, postexposure prophylaxis'''
::* 1. '''For adults'''<ref name="pmid24447897">{{cite journal| author=Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT et al.| title=Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. | journal=Emerg Infect Dis | year= 2014 | volume= 20 | issue= 2 | pages=  | pmid=24447897 | doi=10.3201/eid2002.130687 | pmc=PMC3901462 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24447897  }} </ref>
:::* 1.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
::::* Preferred regimen (1): '''[[Ciprofloxacin]] 500 mg IV q12h'''
::::* Preferred regimen (2): '''[[Doxycycline]] 100 mg IV q12h'''
::::* Preferred regimen (3): [[Levofloxacin]] 750 mg IV q24h
::::* Preferred regimen (4): [[Moxifloxacin]] 400 mg IV q24h
::::* Preferred regimen (5): [[Clindamycin]] 600 mg IV q8h
:::* 1.2 '''Alternatives for penicillin-susceptible strain'''
::::* Preferred regimen (1): [[Amoxicillin]] 1 g IV q8h
::::* Preferred regimen (2): Penicillin VK 500 mg IV q6h
::* 2. '''For children = 1 month'''<ref name="pmid24777226">{{cite journal| author=Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney-Delman D et al.| title=Pediatric anthrax clinical management. | journal=Pediatrics | year= 2014 | volume= 133 | issue= 5 | pages= e1411-36 | pmid=24777226 | doi=10.1542/peds.2014-0563 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24777226  }} </ref>
:::* 2.1 '''For penicillin-resistant strains or prior to susceptibility testing'''
::::* Preferred regimen (1): '''[[Ciprofloxacin]] 30 mg/kg/day PO bid (not to exceed 500 mg/dose)'''
::::* Preferred regimen (2):
:::::* If patients body weight < 45 kg: [[Doxycycline]] 4.4 mg/kg/day PO bid (not to exceed 100 mg/dose)
:::::* If patients body weight > 45 kg: [[Doxycycline]] 100 mg/dose PO bid
::::* Preferred regimen (3): [[Clindamycin]] 30 mg/kg/day PO tid (not to exceed 900 mg/dose)
::::* Preferred regimen (4):
:::::* If patients body weight < 50 kg: [[Levofloxacin]] 16 mg/kg/day PO bid (not to exceed 250 mg/dose)
:::::* If patients body weight > 50 kg: [[Levofloxacin]] 500 mg PO qd
:::* 2.2 '''For penicillin-susceptible strains'''
::::* Preferred regimen (1): '''[[Amoxicillin]] 75 mg/kg/day PO tid (not to exceed 1 g/dose)'''
::::* Preferred regimen (2): [[Penicillin VK]] 50-75 mg/kg/day PO bid or tid
::::* Note: '''Duration of Therapy is 60 days after exposure'''
::* 3. '''For children < 1 month'''
:::* 3.1 '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
::::* 3.1.1 '''For 32–34 weeks gestational age'''
:::::* 3.1.1.1 '''For < 1 week of Age'''
::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 20 mg/kg/day PO bid
::::::* Preferred regimen (2): [[Clindamycin]] 10 mg/kg/day PO bid
:::::* 3.1.1.2 '''For 1–4 week of age '''
::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 20 mg/kg/day PO bid
::::::* Preferred regimen (2): [[Clindamycin]] 15 mg/kg/day PO tid
::::* 3.1.2 '''For 34–37 week gestational age'''
:::::* 3.1.2.1 '''For < 1 week of age'''
::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 20 mg/kg/day PO bid
::::::* Preferred regimen (2): [[Clindamycin]] 15 mg/kg/day PO tid
:::::* 3.1.2.2 '''For 1–4 week of age'''
::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 20 mg/kg/day PO bid
::::::* Preferred regimen (2): [[Clindamycin]] 20 mg/kg/day PO tid
::::* 3.1.3 '''Term newborn infant'''
:::::* 3.1.3.1 '''For < 1 week of age '''
::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 30 mg/kg/day PO bid
::::::* Preferred regimen (2): [[Doxycycline]] 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)
::::::* Preferred regimen (3): [[Clindamycin]] 15 mg/kg/day PO tid
:::::* 3.1.3.2 '''For 1–4 week of Age'''
::::::* Preferred regimen (1): '''[[Ciprofloxacin]]''' 30 mg/kg/day PO bid
::::::* Preferred regimen (2): [[Doxycycline]] 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)
::::::* Preferred regimen (3): [[Clindamycin]] 20 mg/kg/day PO qid
:::* 3.2 '''Alternatives for penicillin-susceptible strains'''
::::* 3.2.1 '''For 32–34 weeks gestational age'''
:::::* 3.2.1.1 '''For < 1 week of age'''
::::::* Alternative regimen (1): [[Amoxicillin]] 50 mg/kg/day PO bid
::::::* Alternative regimen (2): Penicillin Vk  50 mg/kg/day PO bid
:::::* 3.2.1.2 '''For 1–4 week of age'''
::::::* Alternative regimen (1): [[Amoxicillin]] 75 mg/kg/day PO tid
::::::* Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid
::::* 3.2.2 '''For 34–37 week gestational age'''
:::::* 3.2.2.1 '''For < 1 week of age'''
::::::* Alternative regimen (1): [[Amoxicillin]] 50 mg/kg/day PO bid
::::::* Alternative regimen (2): Penicillin Vk 50 mg/kg/day PO bid
:::::* 3.2.2.2 '''For 1–4 week of age'''
::::::* Alternative regimen (1): [[Amoxicillin]] 75 mg/kg/day PO tid
::::::* Alternative regimen (2): Penicillin Vk  75 mg/kg/day PO tid
::::* 3.2.3 '''Term newborn infant'''
:::::* 3.2.3.1 '''For < 1 week of age'''
::::::* Alternative regimen (1): [[Amoxicillin]] 75 mg/kg/day PO tid
::::::* Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid
:::::* 3.2.3.2 '''For 1–4 week of age'''
::::::* Alternative regimen (1): [[Amoxicillin]] 75 mg/kg/day PO tid
::::::* Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO bid or tid
::::::* Note: Duration of therapy is  60 days from exposure
==References==
{{reflist|2}}
==Gallery==
<gallery>
Image: Bacillus_anthracis01.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis02.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis03.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis05.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis06.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis07.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis08.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis09.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis10.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis11.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis12.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis13.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis14.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis15.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis16.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis17.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis18.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis19.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis20.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis21.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Bacillus_anthracis22.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


</gallery>
== References ==
{{Reflist|2}}


==References==
== External links ==
<!-- ---------------------------------------------------------------
{{commons category|Bacillus anthracis}}
See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for a
* [http://patricbrc.org/portal/portal/patric/Taxon?cType=taxon&cId=1392 Bacillus anthracis] genomes and related information at [http://patricbrc.org/ PATRIC], a Bioinformatics Resource Center funded by [http://www.niaid.nih.gov/ NIAID]
discussion of different citation methods and how to generate
* [http://hazard.hegroup.org/query/query_detail.php?c_hazard_ID=64 Hazards in Animal Research Database - ''Bacillus anthracis'']
footnotes using the <ref> & </ref> tags and the {{Reflist}} template
* [http://pathema.jcvi.org/cgi-bin/Bacillus/PathemaHomePage.cgi Pathema-''Bacillus'' Resource]
-------------------------------------------------------------------- -->
{{Reflist}}


[[Category:Bacillaceae]]
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Latest revision as of 15:40, 21 August 2015

style="background:#Template:Taxobox colour;"|Bacillus anthracis
Photomicrograph of Bacillus anthracis (fuchsin-methylene blue spore stain)
Photomicrograph of Bacillus anthracis (fuchsin-methylene blue spore stain)
style="background:#Template:Taxobox colour;" | Scientific classification
Domain: Bacteria
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Bacillaceae
Genus: Bacillus
Species: B. anthracis
Binomial name
Bacillus anthracis
Cohn 1872
This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Anthrax.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The causative agent of anthrax is B. anthracis, a nonmotile, Gram-positive, aerobic or facultatively anaerobic, endospore-forming, rod-shaped bacterium. The spores of B. anthracis, which can remain dormant in the environment for decades, are the infectious form, but this vegetative B. anthracis rarely causes disease.[1] The Bacillus may enter the body through the skin, lungs, gastrointestinal system or by injection, after which they will travel to the lymph nodes. The virulence factors will facilitate the translocation of the toxins to the cytosol. The natural reservoirs of Bacillus anthracis include humans, mammals, herbivores, reptiles, and birds.

Historical background

French physician Casimir Davaine (1812-1882) demonstrated the symptoms of anthrax were invariably accompanied by the microbe B. anthracis.[2] German physician Aloys Pollender (1799–1879) is also credited for this discovery. B. anthracis was the first bacterium conclusively demonstrated to cause disease, by Robert Koch in 1876.[3] The species name anthracis is from the Greek anthrax (ἄνθραξ), meaning "coal" and referring to the most common form of the disease, cutaneous anthrax, in which large, black skin lesions are formed.

Biology

B. anthracis, the causative agent of anthrax, is a nonmotile, Gram-positive, aerobic or facultatively anaerobic, endospore-forming, rod-shaped bacterium approximately 4 μm by 1 μm, although under the microscope it frequently appears in chains of cells. Like other Bacillus, Bacillus anthracis is saprophyte, being able to live in vegetation, air, water and soil.[4]

These bacterial cells may occur isolated, form groups of 2 or more cells in the body, or long chains in cultures.[4] In blood smears, smears of tissues or lesion fluid from diagnostic specimens, these chains are two to a few cells in length. In smears made from in vitro cultures, they can appear as endless strings of cells - responsible for the characteristic tackiness of the colonies and for the flocculating nature of broth cultures. Cell cultures appear with a large, grey and curled structure, resembling a "medusa head".[4]

B. anthracis have a characteristic square-ended appearance, traditionally associated with its vegetative state, although this may not always be very clear. In the presence of oxygen, ideally at 32 - 35 ºC, and towards the end of the exponential phase of growth, one ellipsoidal spore (approximately 2 μm by 1 μm in size) is formed within each cell.[5][4] Commonly the spores will be produced once the cell senses scarcity of nutrients.[6]

The spores of B. anthracis, which can remain dormant in the environment for decades, being resistant to heat and disinfectants, are the infectious form, but vegetative B. anthracis rarely causes disease.[7][4]

In the absence of oxygen and under a high partial pressure of Co2, in the presence of bicarbonate, the vegetative cell secretes its polypeptide capsule. This is one of the two established in vivo virulence factors of B. anthracis. The capsule is also a primary diagnostic aid.[5] Protective antigen (PA) and edema factor (EF) combine to form edema toxin (ET) and PA and lethal factor (LF) combine to form lethal toxin (LT), the active toxins.[8][9]


Photomicrograph depicting a number of Gram-positive, endospore-forming Bacillus anthracis bacteriaCourtesy: Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)[10]
Scanning electron micrograph (SEM) depicted spores from the Sterne strain of Bacillus anthracis bacteriaCourtesy: Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)[11]

Genome structure

B. anthracis has a single chromosome which is a circular, 5,227,293-bp DNA molecule.[12] It also has two circular, extrachromosomal, double-stranded DNA plasmids, pXO1 and pXO2. Both the pXO1 and pXO2 plasmids are required for full virulence and represent two distinct plasmid families.[13]

Feature Chromosome pXO1 pXO2
Size (bp) 5,227,293 181,677 94,829
Number of genes 5,508 217 113
Replicon coding (%) 84.3 77.1 76.2
Average gene length (nt) 800 645 639
G+C content (%) 35.4 32.5 33.0
rRNA operons 11 0 0
tRNAs 95 0 0
sRNAs 3 2 0
Phage genes 62 0 0
Transposon genes 18 15 6
Disrupted reading frame 37 5 7
Genes with assigned function 2,762 65 38
Conserved hypothetical genes 1,212 22 19
Genes of unknown function 657 8 5
Hypothetical genes 877 122 51

pXO1 plasmid

The pXO1 plasmid (182 kb) contains the genes that encode for the anthrax toxin components: pag (protective antigen, PA), lef (lethal factor, LF), and cya (edema factor, EF). These factors are contained within a 44.8-kb pathogenicity island (PAI). The lethal toxin is a combination of PA with LF and the edema toxin is a combination of PA with EF. The PAI also contains genes which encode a transcriptional activator AtxA and the repressor PagR, both of which regulate the expression of the anthrax toxin genes.[13]

pXO2 plasmid

pXO2 encodes a five-gene operon (capBCADE) which synthesizes a poly-γ-D-glutamic acid (polyglutamate) capsule. This capsule allows B. anthracis to evade the host immune system by protecting itself from phagocytosis. Expression of the capsule operon is activated by the transcriptional regulators AcpA and AcpB, located in the pXO2 pathogenicity island (35 kb). Interestingly, AcpA and AcpB expression are under the control of AtxA from pXO1.[13]

Strains

The 89 known strains of B. anthracis include:

  • Sterne strain (34F2; aka the "Weybridge strain"), used by Max Sterne in his 1930s vaccines
  • Vollum strain, formerly weaponized by the US, UK, and Iraq; isolated from cow in Oxfordshire, UK, in 1935
    • Vollum M-36, virulent British research strain; passed through macaques 36 times
    • Vollum 1B, weaponized by the US and UK in the 1940s-60s
    • Vollum-14578, UK biotesting contaminated Gruinard Island, Scotland, in 1940s
    • V770-NP1-R, the avirulent, nonencapsulated strain used in the BioThrax vaccine
  • Anthrax 836, highly virulent strain weaponized by the USSR; discovered in Kirov in 1953
  • Ames strain, isolated from a cow in Texas in 1981; famously used in AMERITHRAX letter attacks (2001)
    • Ames Ancestor
    • Ames Florida
  • H9401, isolated from human patient in Korea; used in investigational anthrax vaccines[14]

Evolution

Whole genome sequencing has made reconstruction of the B. anthracis phylogeny extremely accurate. A contributing factor to the reconstruction is B. anthracis being monomorphic, meaning it has low genetic diversity, including the absence of any measurable lateral DNA transfer since its derivation as a species. The lack of diversity is due to a short evolutionary history that has precluded mutational saturation in single nucleotide polymorphisms.[15]

A short evolutionary time does not necessarily mean a short chronological time. When DNA is replicated, mistakes occur which become genetic mutations. The buildup of these mutations over time leads to the evolution of a species. During the B. anthracis lifecycle, it spends a significant amount of time in the soil spore reservoir stage, a stage in which DNA replication does not occur. These prolonged periods of dormancy have greatly reduced the evolutionary rate of the organism.[15]

Nearest neighbors

B. anthracis belongs to the B. cereus group consisting of the strains: B. cereus, B. anthracis, B. thuringiensis, B. weihenstephanensis, B. mycoides, and B. pseudomycoides. The first three strains are pathogenic or opportunistic to insects or mammals, while the last three are not considered pathogenic. The strains of this group are genetically and phenotypically heterogeneous overall, but some of the strains are more closely related and phylogenetically intermixed at the chromosome level. The B. cereus group generally exhibits complex genomes and most carry varying numbers of plasmids.[13]

B. cereus is a soil-dwelling bacterium which can colonize the gut of invertebrates as a symbiont[16] and is a frequent cause of food poisoning[17] It produces an emetic toxin, enterotoxins, and other virulence factors.[18] The enterotoxins and virulence factors are encoded on the chromosome, while the emetic toxin is encoded on a 270-kb plasmid, pCER270.[13]

B. thuringiensis is an insect pathogen and is characterized by production of parasporal crystals of insecticidal toxins Cry and Cyt.[19] The genes encoding these proteins are commonly located on plasmids which can be lost from the organism, making it indistinguishable from B. cereus.[13]

Pseudogene

PlcR is a global transcriptional regulator which controls most of the secreted virulence factors in B. cereus and B. thuringiensis. It is chromosomally encoded and is ubiquitous throughout the cell.[20] In B. anthracis, however, the plcR gene contains a single base change at position 640, a nonsense mutation, which creates a dysfunctional protein. While 1% of the B. cereus group carries an inactivated plcR gene, none of them carries the specific mutation found only in B. anthracis.[21]

The plcR gene is part of a two-gene operon with papR.[22][23] The papR gene encodes a small protein which is secreted from the cell and the reimported as a processed heptapeptide forming a quorum-sensing system.[23][24] The lack of PlcR in B. anthracis is a principle characteristic differentiating it from other members of the B. cereus group. While B. cereus and B. thuringiensis depend on the plcR gene for expression of their virulence factors, B. anthracis relies on the pXO1 and pXO2 plasmids for its virulence.[13]

Laboratory research

Components of tea, such as polyphenols, have the ability to inhibit the activity both of B. anthracis and its toxin considerably; spores, however, are not affected. The addition of milk to the tea completely inhibits its antibacterial activity against anthrax.[25] Activity against the B. athracis in the laboratory does not prove that drinking tea affects the course of an infection, since it is unknown how these polyphenols are absorbed and distributed within the body.

Recent research

Advances in genotyping methods have led to improved genetic analysis for variation and relatedness. These methods include multiple-locus variable-number tandem repeat analysis (MLVA) and typing systems using canonical single-nucleotide polymorphisms. The Ames ancestor chromosome was sequenced in 2003[12] and contributes to the identification of genes involved in the virulence of B. anthracis. Recently, B. anthracis isolate H9401 was isolated from a Korean patient suffering from gastrointestinal anthrax. The goal of the Republic of Korea is to use this strain as a challenge strain to develop a recombinant vaccine against anthrax.[14]

The H9401 strain isolated in the Republic of Korea was sequenced using 454 GS-FLX technology and analyzed using several bioinformatics tools to align, annotate, and compare H9401 to other B. anthracis strains. The sequencing coverage level suggests a molecular ratio of pXO1:pXO2:chromosome as 3:2:1 which is identical to the Ames Florida and Ames Ancestor strains. H9401 has 99.679% sequence homology with Ames Ancestor with an amino acid sequence homology of 99.870%. H9401 has a circular chromosome (5,218,947 bp with 5,480 predicted ORFs), the pXO1 plasmid (181,700 bp with 202 predicted ORFs), and the pXO2 plasmid (94,824 bp with 110 predicted ORFs).[14] As compared to the Ames Ancestor chromosome above, the H9401 chromosome is about 8.5 kb smaller. Due to the high pathogenecity and sequence similarity to the Ames Ancestor, H9401 will be used as a reference for testing the efficacy of candidate anthrax vaccines by the Repbulic of Korea.[14]

Host interactions

As with most other pathogenic bacteria, B. anthracis must acquire iron to grow and proliferate in its host environment. The most readily available iron sources for pathogenic bacteria are the heme groups used by the host in the transport of oxygen. To scavenge heme from host hemoglobin and myoglobin, B. anthracis uses two secretory siderophore proteins, IsdX1 and IsdX2. These proteins can separate heme from hemoglobin, allowing surface proteins of B. anthracis to transport it into the cell.[26]

Origin

Bacillus anthracis is thought to have originated in Egypt and Mesopotamia. Many scholars think that in Moses’ time, during the 10 plagues of Egypt, anthrax may have caused what was known as the fifth plague, described as a sickness affecting horses, cattle, sheep, camels and oxen.

Tropism

After entering the body (through the skin, lungs, gastrointestinal tract or by injection), B. anthracis spores are believed to germinate locally or be transported by phagocytic cells to the lymphatics and regional lymph nodes, where they germinate.[9][27] After binding to cell surface receptors, the PA portion of the complexes facilitates translocation of the toxins to the cytosol.[28][9]

Natural Reservoir

Natural reservoirs of Bacillus anthracis include:[5][4][9]

  • Humans
  • Mammals
  • Herbivores
  • Reptiles
  • Birds


References

  1. ↑ Sean V. Shadomy & Theresa L. Smith (2008). "Zoonosis update. Anthrax". Journal of the American Veterinary Medical Association. 233 (1): 63–72. doi:10.2460/javma.233.1.63. PMID 18593313. Unknown parameter |month= ignored (help)
  2. ↑ Théodoridès, J (April 1966). "Casimir Davaine (1812-1882): a precursor of Pasteur". Medical history. 10 (2): 155–65. doi:10.1017/S0025727300010942. PMC 1033586. PMID 5325873.
  3. ↑ Koch, R. (1876) "Untersuchungen über Bakterien: V. Die Ätiologie der Milzbrand-Krankheit, begründet auf die Entwicklungsgeschichte des Bacillus anthracis" (Investigations into bacteria: V. The etiology of anthrax, based on the ontogenesis of Bacillus anthracis), Cohns Beitrage zur Biologie der Pflanzen, vol. 2, no. 2, pages 277–310.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Bhatnagar, Rakesh; Batra, Smriti (2001). "Anthrax Toxin". Critical Reviews in Microbiology. 27 (3): 167–200. doi:10.1080/20014091096738. ISSN 1040-841X.
  5. ↑ 5.0 5.1 5.2 "Anthrax in Humans and Animals" (PDF).
  6. ↑ Spencer RC (2003). "Bacillus anthracis". J Clin Pathol. 56 (3): 182–7. PMC 1769905. PMID 12610093.
  7. ↑ Sean V. Shadomy & Theresa L. Smith (2008). "Zoonosis update. Anthrax". Journal of the American Veterinary Medical Association. 233 (1): 63–72. doi:10.2460/javma.233.1.63. PMID 18593313. Unknown parameter |month= ignored (help)
  8. ↑ Mahtab Moayeri & Stephen H. Leppla (2004). "The roles of anthrax toxin in pathogenesis". Current opinion in microbiology. 7 (1): 19–24. doi:10.1016/j.mib.2003.12.001. PMID 15036135. Unknown parameter |month= ignored (help)
  9. ↑ 9.0 9.1 9.2 9.3 "Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults".
  10. ↑ "http://phil.cdc.gov/phil/details.asp". External link in |title= (help)
  11. ↑ "http://phil.cdc.gov/phil/details.asp". External link in |title= (help)
  12. ↑ 12.0 12.1 Read, TD (May 1, 2003). "The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria". Nature. 423 (6935): 81–6. doi:10.1038/nature01586. PMID 12721629. Unknown parameter |coauthors= ignored (help)
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 Kolstø, Anne-Brit; Tourasse, Nicolas J.; Økstad, Ole Andreas (1 October 2009). "What Sets Apart from Other Species?". Annual Review of Microbiology. 63 (1): 451–476. doi:10.1146/annurev.micro.091208.073255.
  14. ↑ 14.0 14.1 14.2 14.3 Chun, J.-H.; Hong, K.-J.; Cha, S. H.; Cho, M.-H.; Lee, K. J.; Jeong, D. H.; Yoo, C.-K.; Rhie, G.-e. (18 July 2012). "Complete Genome Sequence of Bacillus anthracis H9401, an Isolate from a Korean Patient with Anthrax". Journal of Bacteriology. 194 (15): 4116–4117. doi:10.1128/JB.00159-12. PMC 3416559. PMID 22815438.
  15. ↑ 15.0 15.1 Keim, Paul; Gruendike, Jeffrey M.; Klevytska, Alexandra M.; Schupp, James M.; Challacombe, Jean; Okinaka, Richard (1 December 2009). "The genome and variation of Bacillus anthracis". Molecular Aspects of Medicine. 30 (6): 397–405. doi:10.1016/j.mam.2009.08.005. PMC 3034159. PMID 19729033.
  16. ↑ Jensen, G. B.; Hansen, B. M.; Eilenberg, J.; Mahillon, J. (18 July 2003). "The hidden lifestyles of Bacillus cereus and relatives". Environmental Microbiology. 5 (8): 631–640. doi:10.1046/j.1462-2920.2003.00461.x. PMID 12871230.
  17. ↑ Drobniewski, FA (October 1993). "Bacillus cereus and related species". Clinical Microbiology Reviews. 6 (4): 324–38. PMC 358292. PMID 8269390.
  18. ↑ Stenfors Arnesen, Lotte P.; Fagerlund, Annette; Granum, Per Einar (1 July 2008). "From soil to gut: and its food poisoning toxins". FEMS Microbiology Reviews. 32 (4): 579–606. doi:10.1111/j.1574-6976.2008.00112.x. PMID 18422617.
  19. ↑ Schnepf, E; Crickmore, N; Van Rie, J; Lereclus, D; Baum, J; Feitelson, J; Zeigler, DR; Dean, DH (September 1998). "Bacillus thuringiensis and its pesticidal crystal proteins". Microbiology and molecular biology reviews : MMBR. 62 (3): 775–806. PMC 98934. PMID 9729609.
  20. ↑ Agaisse, H; Gominet, M; Okstad, OA; Kolstø, AB; Lereclus, D (June 1999). "PlcR is a pleiotropic regulator of extracellular virulence factor gene expression in Bacillus thuringiensis". Molecular microbiology. 32 (5): 1043–53. doi:10.1046/j.1365-2958.1999.01419.x. PMID 10361306.
  21. ↑ Slamti, L; Perchat, S; Gominet, M; Vilas-Bôas, G; Fouet, A; Mock, M; Sanchis, V; Chaufaux, J; Gohar, M; Lereclus, D (June 2004). "Distinct mutations in PlcR explain why some strains of the Bacillus cereus group are nonhemolytic". Journal of bacteriology. 186 (11): 3531–8. doi:10.1128/JB.186.11.3531-3538.2004. PMC 415780. PMID 15150241.
  22. ↑ Okstad, OA; Gominet, M; Purnelle, B; Rose, M; Lereclus, D; Kolstø, AB (November 1999). "Sequence analysis of three Bacillus cereus loci carrying PIcR-regulated genes encoding degradative enzymes and enterotoxin". Microbiology (Reading, England). 145 (11): 3129–38. PMID 10589720.
  23. ↑ 23.0 23.1 Slamti, L; Lereclus, D (Sep 2, 2002). "A cell-cell signaling peptide activates the PlcR virulence regulon in bacteria of the Bacillus cereus group". The EMBO Journal. 21 (17): 4550–9. doi:10.1093/emboj/cdf450. PMC 126190. PMID 12198157.
  24. ↑ Bouillaut, L; Perchat, S; Arold, S; Zorrilla, S; Slamti, L; Henry, C; Gohar, M; Declerck, N; Lereclus, D (June 2008). "Molecular basis for group-specific activation of the virulence regulator PlcR by PapR heptapeptides". Nucleic Acids Research. 36 (11): 3791–801. doi:10.1093/nar/gkn149. PMC 2441798. PMID 18492723.
  25. ↑ "Anthrax and tea". Society for Applied Microbiology. 2011-12-21. Retrieved 2011-12-21.
  26. ↑ Maresso AW, Garufi G, Schneewind O (2008). "Bacillus anthracis Secretes Proteins That Mediate Heme Acquisition from Hemoglobin". PLOS Pathogens. 4(8): e1000132.
  27. ↑ Ross, Joan M. (1957). "The pathogenesis of anthrax following the administration of spores by the respiratory route". The Journal of Pathology and Bacteriology. 73 (2): 485–494. doi:10.1002/path.1700730219. ISSN 0368-3494.
  28. ↑ Moayeri, M (2004). "The roles of anthrax toxin in pathogenesis". Current Opinion in Microbiology. 7 (1): 19–24. doi:10.1016/j.mib.2003.12.001. ISSN 1369-5274.

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