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POST-EXPOSURE PROPHYLAXIS AND TREATMENT OF POTENTIALLY HARMFUL AGENTS TO SOCIETY ANTHRAX (drugs are listed in order of preference) 21, 22 Post-Exposure Prophylaxis: (duration of prophylaxis: 60 days

1 POST-EXPOSURE PROPHYLAXIS AND TREATMENT OF POTENTIALLY HARMFUL AGENTS TO SOCIETY ANTHRAX (drugs are listed in order of preference) 21, 22 Post-Exposure Prophylaxis: (duration of prophylaxis: 60 days after exposure) Ciprofloxacin 15 mg/kg/dose PO BID (max: 500 Doxycycline: <45 kg: 2.2mg/kg/dose PO BID (max: 100 > 45 kg: 100 mg/dose PO BID Clindamycin 10 mg/kg/dose PO TID (max: 900 Levofloxacin: <50 kg: 8 mg/kg/dose PO BID (max: 250 >50 kg: 500 mg PO once daily Amoxicillin 75 mg/kg/day PO divided into 3 doses (max: 1 gram/dose) Penicillin VK mg/kg/day PO divided every 6-8 hours Cutaneous Anthrax (Duration for naturally acquired infection: 7-10 days Duration for bioterrorism: 60 days from onset of illness) Ciprofloxacin 15 mg/kg/dose PO BID (max 500 mg/dose ) Doxycycline: o < 45kg: 2.2mg/kg/dose PO BID (max: 100 o 45kg: 100mg/dose PO BID Clindamycin 30 mg/kg/day PO divided every 8 hours (max: 600 Levofloxacin: o <50 kg: 8 mg/kg/dose PO BID (max: 250 o >50 kg: 500 mg PO once daily Amoxicillin 75 mg/kg/day PO divided every 8 hours (max: 1 gram/dose) Penicillin VK mg/kg/day PO divided every 6-8 hours Post-Exposure Prophylaxis: (duration of prophylaxis: 60 days after exposure) Ciprofloxacin 500mg/dose PO BID Doxycycline 100mg/dose PO BID Levofloxacin 750 mg PO once daily Moxifloxacin 400 mg PO once daily Clindamycin 600 mg PO every 8 hours Amoxicillin 1 gram PO every 8 hours Penicillin VK 500 mg every 6 hours Cutaneous Anthrax Ciprofloxacin 500mg/dose PO BID Doxycycline 100mg/dose PO BID Levofloxacin 750 mg PO once daily Moxifloxacin 400 mg PO once daily Clindamycin 600 mg PO every 8 hours Amoxicillin 1 gram PO every 8 hours Penicillin VK 500 mg every 6 hours

2 Systemic Anthrax Treatment (when meningitis has been ruled out): Duration of therapy: 14 days or longer until clinically stable Route of admin: IV 1 of the following bactericidal drugs: Ciprofloxacin 30 mg/kg day divided every 8 hours (max: 400 or Meropenem 60 mg/kg/day divided every 8 hours (max: 2 gram/dose) or Levofloxacin: <50 kg: 20 mg/kg/day divided every 12 hours (max: 250 ; >50 kg: 500 mg once daily or Imipenem 100 mg/kg/day divided every 6 hours (max: 1 gram/dose) or Vancomycin 60 mg/kg/day IV divided every 8 hours (monitor serum concentration) Penicillin G 400,000 units/kg/day divided every 4 hours (max: 4 MU/dose) or Ampicillin 200 mg/kg/day divided every 6 hours (max: 3 gram/dose) PLUS 1 of the following protein synthesis inhibitors: Clindamycin 40 mg/kg/day divided every 8 hours (max: 900 or Linezolid: <12 years old: 30 mg/kg/day divided every 8 hours; 12 years old: 30 mg/kg/day divided every 12 hours (max: 600 or Doxycycline: < 45 kg: loading dose 4.4 mg/kg/day (max: 200 mg) and maintenance dose 4.4 mg/kg/day divided every 12 hours (max: 100 ; 45 kg: loading dose 200 mg/day and maintenance dose 100 mg every 12 hrs or Rifampin 20 mg/kg/day divided every 12 hours (max: 300 (May switch to oral therapy and dosing when clinically appropriate) Systemic Anthrax Treatment (when meningitis has been ruled out): Duration of therapy; 14 days or longer until clinically stable Route of admin: IV 1 of the following bactericidal drugs: Ciprofloxacin 400 mg every 8 hours or Levofloxacin 750 mg once daily or Moxifloxacin 400 mg once daily or Meropenem 2 gram every 8 hours or Imipenem 1 gram every 6 hours or Doripenem 500 mg every 8 hours or Vancomycin 60 mg/kg/day IV divided every 8 hours (target trough level mcg/ml) Penicillin G, 4 million units every 4 hours or Ampicillin 3 gram every 6 hours PLUS 1 of the following protein synthesis inhibitors: Clindamycin 900 mg every 8 hours or Linezolid 600 mg every 12 hours or Doxycycline 200 mg initially, then 100 mg every 12 hours or Rifampin 600 mg every 12 hours (May switch to oral therapy and dosing when clinically appropriate) 2

3 Treatment of Anthrax with confirmed/possible meningitis: (Duration of therapy: 2-3 weeks until clinically stable) Route of admin: IV 1 fluoroquinolone Ciprofloxacin 30 mg/kg day divided every 8 hours (max: 400 or Levofloxacin: <50 kg: 16 mg/kg/day divided every 12 hours (max: 250 ; >50 kg: 500 mg once daily or Moxifloxacin: o 3 mo to < 2 years old: 12 mg/kg/day divided every 12 hours (max: 200 o 2-5 years old: 10 mg/kg/day divided every 12 hours (max: 200 o 6-11 years old: 8 mg/kg/day divided every 12 hours (max: 200 o years old: < 45 kg: 8 mg/kg/day divided every 12 hours (max: 200 ; 45 kg: 400 mg once daily PLUS 1 beta-lactam or glycopeptide Meropenem 120 mg/kg/day divided every 8 hours (max: 2 gram/dose) or Imipenem 100 mg/kg/day divided every 6 hours (max: 1 gram/dose) or Doripenem 120 mg/kg/day divided every 8 hours (max: 1 gram/dose) or Vancomycin 60 mg/kg/day divided every 8 hours (monitor serum concentration) Treatment of Anthrax with confirmed/possible meningitis: (Duration of therapy: 2-3 weeks until clinically stable) Route of admin: IV 1 fluoroquinolone Ciprofloxacin 400 mg every 8 hours or Levofloxacin 750 mg once daily or Moxifloxacin 400 mg once daily PLUS 1 beta-lactam Meropenem 2 gram every 8 hours or Imipenem 1 gram every 6 hours or Doripenem 500 mg every 8 hours Penicillin G, 4 million units every 4 hours or Ampicillin 3 gram every 6 hours PLUS 1 protein synthesis inhibitor Linezolid 600 mg every 12 hours or Clindamycin 900 mg every 8 hours or Rifampin 600 mg every 12 hours or Chloramphenicol 1 gram every 6-8 hours Penicillin G 400,000 units/kg/day divided every 4 hours (max: 4 MU/dose) or 3

4 BOTULISUM BRUCELLOSIS LASSA FEVER Ampicillin 400 mg/kg/day divided every 6 hours (max: 3 gram/dose) PLUS 1 protein synthesis inhibitor Linezolid: <12 years old: 30 mg/kg/day divided every 8 hours; 12 years old: 30 mg/kg/day divided every 12 hours (max: 600 or Clindamycin 40 mg/kg/day divided every 8 hours (max: 900 or Rifampin 20 mg/kg/day divided every 12 hours (max: 300 or Chloramphenicol 100 mg/kg/day divided every 6 hours Botulinum Equine Trivalent Antitoxin Treatment if >8 yoa: Doxycycline PO 200mg/day x 6 weeks + Streptomycin IM 1g/day x 2 weeks or Gentamycin 3-5mg/kg/day IM or IV x 1 week Doxycycline PO 200mg/d or TMP-SMX 2DS/d x 6 weeks + Rifampin PO 15-20mg/kg/day x 6 weeks Treatment if <8 yoa: TMP-SMX PO 5 mg/kg/dose BID x 45 days + Gentamicin IV/IM 2 mg/kg/dose q8h x 2 wks Ribavirin 30mg/kg IV x 1 dose (max dose: 2g), then 16mg/kg/dose Q 6 hours x 4 days (max dose: 1g), then 8mg/kg/dose Q 8 hours x 6 days (max dose: 500mg) 5 Botulinum Equine Trivalent Antitoxin 3 Doxycycline PO 200mg/day x 6 weeks + Streptomycin IM 1g/day x 2 weeks or Gentamycin 3-5mg/kg/day IM or IV x 1 week Doxycycline PO 200mg/day x 6 weeks + Rifampin PO 15-20mg/kg/day x 6 weeks 4 Ribavirin 33mg/kg IV x 1 dose (max dose: 2g), then 16mg/kg/dose Q 6 hours x 4 days (max dose: 1g), then 8mg/kg/dose Q 8 hours x 6 days (max dose: 500mg) 6 4

5 PLAGUE 19, 20 Q FEVER Post-Exposure Prophylaxis: Doxycycline: o <45kg: 2.2mg/kg/dose PO BID x 10 days o 45kg: 100mg/dose PO BID x 10 days Ciprofloxacin 20mg/kg/dose PO BID x 10 days Chloramphenicol 25mg/kg/dose PO QID x 10 days (avoid if <2yoa) Streptomycin 15mg/kg/dose IM BID (max daily dose: 2g) x 10 days Gentamicin 2.5mg/kg/dose IM or IV TID x 10 days Doxycycline: o <45kg: 2.2mg/kg/dose IV BID (max: 200mg/day) x 10 days o 45kg: 100mg/dose IV BID x 10 days Ciprofloxacin 15mg/kg/dose IV BID x 10 days Chloramphenicol 25mg/kg/dose IV QID x 10 days (avoid if <2yoa) Post-Exposure Prophylaxis: Doxycycline 100mg/dose PO BID x 10 days Ciprofloxacin 500mg/dose PO BID x 10 days Chloramphenicol 25mg/kg/dose PO QID x 10 days Streptomycin 1g/dose IM BID x 10 days Gentamicin 5mg/kg/dose IM or IV once daily or 2mg/kg LD x followed by 1.17mg/kg/dose IM or IV TID x 10 days Doxycycline 100mg/dose IV BID x 10 days Ciprofloxacin 400mg/dose IV BID x 10 days Chloramphenicol 25mg/kg/dose IV QID x 10 days 7 Prophylaxis: Doxycycline 100mg/dose PO BID x 5 days (Start 8-12 days after exposure) Tetracycline 500mg/dose PO QID x 5 days For pregnant women: Sulfamethoxazole-Trimethoprim 800mg-160mg PO BID for the duration of pregnancy 5

6 17, 18 SHIGELLOSIS SMALLPOX Acute Treatment : >= 8 years old: Doxycycline 2.2 mg/kg/dose PO BID x 14 days (max 100 < 8 years old with high risk (hospitalized or have severe illness, preexisting heart valvulopathy, immunocompromised, or delayed Q fever diagnosis who have experienced illness for >14 days without resolution of symptoms): Doxycycline 2.2 mg/kg/dose PO BID x 14 days (max 100 < 8 years old with mild/uncomplicated illness: Doxycycline 2.2 mg/kg/dose PO BID x 5 days (max 100 If patient remains febrile after 5 days of treatment: Co-trimoxazole: trimethoprim 4 mg/kg/dose PO BID x 2 weeks (max: sulfamethoxazole 800 First line: Ciprofloxacin 15 mg/kg PO Q12 hours x 3- days Alternatives (if Ciprofloxacin resistant): Ceftriaxone mg/kg IM once daily x 2-5 days Azithromycin 6-20 mg/kg PO once daily x 1-5 days Post-Exposure Prophylaxis: Smallpox Vaccine (not recommended in infants) 6 Doxycycline: o <45kg: 2.2mg/kg/dose PO BID x 14 days o 45kg: 100mg/dose PO BID x 14 days Ciprofloxacin 15mg/kg/dose PO BID x 14 days (max: 1g/day) Acute Doxycycline 100mg PO BID x 14 days First line: Ciprofloxacin 500mg/dose PO BID x 3 days Alternatives (if Ciprofloxacin resistant):azithromycin grams PO once daily x 1-5 days Post-Exposure Prophylaxis: Smallpox Vaccine 10 Doxycycline 100mg/dose PO BID x 14 days Ciprofloxacin 500mg/dose PO BID x 14 days 6

7 TULAREMIA TYPHOID FEVER 23 Gentamicin 2.5mg/kg/dose IM or IV TID x 10 days Drug of choice Streptomycin 15mg/kg/dose IM BID x 10 days (max: 2g/day) - alternative Doxycycline: o <45kg: 2.2mg/kg/dose IV BID x days o 45kg: 100mg/dose IV BID x days Chloramphenicol 15mg/kg/dose IV QID x days Ciprofloxacin 15mg/kg/dose IV BID x 10 days (max: 1g/day) (can switch to oral therapy when clinically indicated) Treatment (Complicated Typhoid Fever): 24 Ceftriaxone 75mg/kg/day IV or IM x days 23 Gentamicin 5mg/kg/dose IM or IV once daily x 10 days Streptomycin 1g/dose IM BID x 10 days alternative Doxycycline 100mg/dose IV BID x at least 15 days Chloramphenicol 15mg/kg/dose IV QID x days Ciprofloxacin 400mg/dose IV BID x days 11 (can switch to oral therapy when clinically indicated) Treatment (Uncomplicated Typhoid Fever): 24 Ciprofloxacin 7.5mg/kg/dose PO BID x 5-7 days Ofloxacin 7.5mg/kg/dose PO BID x 5-7 days Chloramphenicol mg/kg/dose PO QID x days Amoxicillin mg/kg/dose TID x days Trimethoprim-Sulfamethoxazole 4/20-20/100 mg/kg/dose PO BID x days Cefixime mg/kg/dose PO BID x 7-14 days Azithromycin 8-10mg/kg/dose PO once daily x 7 days Ceftriaxone 75 mg/kg/day IV or IM x days (complicated) 9 7

8 ARSINE No antidote Oxygen by mask Aerosolized bronchodilators Racemic epinephrine aerosol for children who develop stridor: mL of 2.25% racemic epinephrine in 2.5mL water; repeat Q 20 min PRN No antidote Oxygen by mask Aerosolized bronchodilators 2 ARSENIC Dimercaprol: o Mild: 2.5mg/kg/dose IM Q6 hours x 2 days, then Q12 hours x 1 day, then Q24 hours x 10 days o Severe: 3mg/kg/dose Q4 hours x 2 days, then Q6 hours x 1 day, then Q12 hours x 10 days 12 Dimercaprol 3-5mg/kg/dose IM Q 4-6 hours until symptoms resolve or another chelator is substituted 25 DMSA 10mg/kg/dose Q 8 hours x 5 days, then 10mg/kg/dose Q 12 hours x 14 days 2 CARBON MONOXIDE 100% Oxygen Hyperbaric oxygen 100% Oxygen Hyperbaric oxygen 2,13 HYDROGEN CYANIDE Amyl Nitrate Perles: break onto a gauze pad and hold under nose and inhale for 30 seconds Q minute and use a new perle Q 3 minutes Next, give sodium nitrite IV: ml/kg (max: 10mL) infused over 5 minutes Then give sodium thiosulfate IV: 1.65mL/kg of a 25% solution. Half the dose may be repeated 30 minutes later if inadequate response. Amyl Nitrate Perles: break onto a gauze pad and hold under nose, over the Ambu-valve intake, or placed under the lip of the face mask, and inhale for 30 seconds Q minute and use a new perle Q 3 minutes 26 Next, give Sodium nitrite IV: 10 ml of 3% solution infused over 5 minutes Then give sodium thiosulfate IV: 50mL of 25% solution infused over minutes. Half the dose may be repeated 30 minutes later if inadequate response. 2 ETHYLENE GLYCOL N/A IV Ethanol: 10% ethanol IV over minutes Oral Ethanol: 20% ethanol solution PO until ethanol level of mg/dl Fomepizole (4-methylpyrazole) 15mg/kg LD IV, 12 hours later 10mg/kg/dose Q 12 hours x 4 doses, then 15mg/kg/dose Q 12 hours as long as indicated 2 MERCURY Dimercaprol 3-5 mg/kg/dose IM Q 4 hours x 2 days, then Dimercaprol 3-5 mg/kg/dose IM Q 4 hours x 2 days, then 2.5-8

9 2.5-3mg/kg/dose IM Q 6 hours x 2 days, then 2.5-3mg/kg/dose IM Q 12 hours x 7 days Penicillamine 20-30mg/kg/day PO QD or BID AC DMSA 10mg/kg/dose PO Q 8 hours x 5 days, then 10mg/kg/dose PO BID x 14 days 3mg/kg/dose IM Q 6 hours x 2 days, then 2.5-3mg/kg/dose IM Q 12 hours x 7 days Penicillamine 15-40mg/kg/day (don t exceed mg PO Q6H AC) x 1 week until decline in urine mercury levels DMSA 10mg/kg/dose PO Q 8 hours x 5 days, then 10mg/kg/dose PO BID x 14 days 14 PARAQUAT Activated Charcoal (1-12 yoa): 1-2g/kg or 25-50g Ingestion of food or dirt Activated Charcoal: g Ingestion of food or dirt 2,12 SARIN 0-2 yoa: Atropine 5 mg single dose IM or 0.02mg/kg IV 2-PAM Cl 15mg/kg IV slowly Infant < 70kg: 15mg/kg IV repeated twice at hourly intervals Above 70kg: 1gm IV repeated twice at hourly intervals PRN <20 kg: 15mg/kg IM >20kg 600mg auto injector IM 2-10 yoa: Atropine 1 mg single dose 2-PAM Cl: 15mg/kg IV slowly >10 yoa: Atropine 2.0mg single dose 2-PAM Cl: 15mg/kg IV slowly Exposure: Latent o Clinical: None o None, observe for one hour with vapor and for 18 hours if liquid or unknown exposure. Exposure: Mild o Clinical: Miosis with dim and/or blurred vision, rhinorrhea, shortness of breath. o Miosis and rhinorrhea, observation only. Shortness of breath: one MARK 1 kit or Atropine 2mg IM/IV and 2-PAM CI 600mg IM or 1 gm IV. Exposure: Moderate o Clinical: As above but more severe; or vomiting and diarrhea. o One MARK 1 Kit or Atropine 2mg IM/IV and 2- PAM CI 600mg IM or 1 gm IV. Exposure: Severe o Clinical: Above plus unconsciousness, flaccid paralysis, respiratory distress, cyanosis, seizures or severe effects in two or more organ systems. o Oxygen, bag mask, intubate after three MARK 1 kits or Atropine 6mg IM and 2-PAM CI 1800mg IM or 1 gm 2-PAM CI IV repeated twice at hourly intervals. Repeat 2mg Atropine at 3-5 minute intervals until atropinized. Diazepam for seizures. 9

10 SOMAN 0-2 yoa: Atropine 5 mg single dose IM or 0.02mg/kg IV 2-PAM Cl 15mg/kg IV slowly Infant < 70kg: 15mg/kg IV repeated twice at hourly intervals Above 70kg: 1gm IV repeated twice at hourly intervals PRN <20 kg: 15mg/kg IM >20kg 600mg auto injector IM 2-10 yoa: Atropine 1 mg single dose 2-PAM Cl: 15mg/kg IV slowly >10 yoa: Atropine 2.0mg single dose 2-PAM Cl: 15mg/kg IV slowly Atropine 2-6 mg IM (depending on severity, as above) 27 2-PAM Cl: 15mg/kg (max: 1g) IV slowly 2 [Adjustments] Elderly, frail or medically compromised: 1mg and repeat as necessary Atropine 2-6 mg IM (depending on severity, table above) 27 2-PAM Cl: 15mg/kg (max: 1g) IV slowly 2 [Adjustments] Elderly, frail or medically compromised: 1mg and repeat as necessary SUPER WARFARIN (Bromadiolone, Brodifacoum, Diphenadione, Chlorophacinone, and Pindone) Activated Charcoal 15-30gm (1-2mg/kg in infants) PO Life-Threatening Hemorrhage: Phytonadione Activated Charcoal g PO Life-Threatening Hemorrhage: Phytonadione (Vitamin K1) 10mg IM or SC 15 TABUN 0-2 yoa: Atropine 5 mg single dose IM or 0.02mg/kg IV 2-PAM Cl 15mg/kg IV slowly Infant < 70kg: 15mg/kg IV repeated twice at hourly intervals Above 70kg: 1gm IV repeated twice at hourly intervals PRN <20 kg: 15mg/kg IM Atropine 2-6 mg IM (depending on severity, table above) 2-PAM Cl: 15mg/kg (max: 1g) IV slowly 2 [Adjustments] Elderly, frail or medically compromised: 1mg and repeat as necessary 27 10

11 >20kg 600mg auto injector IM 2-10 yoa: Atropine 1 mg single dose 2-PAM Cl: 15mg/kg IV slowly >10 yoa: Atropine 2.0mg single dose 2-PAM Cl: 15mg/kg IV slowly 11

12 References: 1. Abramowicz, Mark. Post-Exposure Anthrax Prophylaxis. The Medical Letter, Inc. 2001; 44: W A. 2. Department of Health and Human Services Centers for Disease Control and Prevention U.S. Government. 06 Feb Arnon SS, Schecter R, Inglesby TV, et al. Botulinum Toxin as a Biological Weapon Medical and Public Management. JAMA. 2001; 285: Long: Principles and Practice of Pediatric Infectious Diseases Churchill Livingstone, An Imprint of Elsevier. 06 Feb Markenson, David. The Treatment of Children Exposed to Pathogens Linked to Bioterrorism. Infect Dis Clin N Am 2005; 19: Clinical Pharmacology Online Gold Standard Media. 06 Feb Inglesby TV, Dennis DT, Henderson DA et al. Plague as a Biological Weapon Medical and Public Health Management. JAMA 2000; 283: Interim Guidelines for Action in the Event of a Deliberate Release: Q FEVER. HPA Centre for Infections. Vers Mandell, Bennet, & Dollin: Principles and Practice of Infectious Diseases, 6th ed Churchill Livingstone, An Imprint of Elsevier. 6 Feb Henderson DA, Inglesby TV, Bartlett JG, et al. Smallpox as a Biological weapon Medical and Public Health Management. JAMA. 1999; 281: Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a Biological Weapon Medical and Public Health Management. JAMA. 2001; 285: Taketome CK, Hodding JK, and Kraus DM. LEXI-COMP S Pediatric Dosage Handbook 12th ed Lexi-Comp Inc. 13. World Health Organization Feb Diner, Barry. Toxicity, Mercury EMedicine.com, Inc. 06 Feb Management of Rodenticide Poisoning Indegene Lifesystems Pvt. Ltd. 6 Feb Leikin JB and Paloucek FB. Leikin & Paloucek s Poisoning & Toxicology Handbook 3rd ed Guidelines for the control of shigellosis, including epidemics due to Shigella dysenteria type 1. World Health Organization Health Advisory: Increased Shigella Cases: Ciprofloxacin-Resistance Common, Update 12/22/14. San Francisco Department of Public Health Anderson A, Bijlmer H, Fournier PE, et al. Diagnosis and Management of Q Fever United States, 2013: Recommendations from CDC and the Q Fever Working Group. Center for Disease Control and Prevention Moodie CE, Thompson HA, Meltzer MI, Swerdlow DL. Prophylaxis after exposure to Coxiella burnetii. Emerg Infect Dis [serial on the Internet] Oct. Available from Katherine AH, Mary EW, Sean VS, et al. Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults. Emerging Infectious Disease journal 2014;20. Available from Bradley JS, Peacock G, Krug SE, et al. Pediatric Anthrax Clinical Management. Pediatrics Available from WHO Guidelines on Tularaemia. World Health Organization Guidelines for the Management of Typhoid Fever. World Health Organization July Nelson LS, Lewin NA, Howland MA, et al. Goldfrank s Toxicological Emergencies. McGraw-Hill, New York ATSDR Toxicological profile for hydrogen cyanide (update). U.S. Department of Health and Human Services. Agency for Toxic Substances and Disease Registry 27. Zebra Packet 2010: Biological, Chemical, and Radiological Terrism information for Clinicians. County of San Diego Health and Human Services Agency. 12

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