6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
A) Remove contaminated clothing. Bag soiled clothing or dressings in polyethylene until autoclaved or incinerated. Anyone handling contaminated material should wash exposed area extremely thoroughly with soap and water. B) ACTIVATED CHARCOAL 1) There is no experience in the use of activated charcoal after ingestion of anthrax-contaminated food. Activated charcoal might be of use after recent ingestion. 2) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002). 1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
3) CHARCOAL DOSE a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005). 1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
b) ADVERSE EFFECTS/CONTRAINDICATIONS 1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
6.5.2) PREVENTION OF ABSORPTION
A) ACTIVATED CHARCOAL 1) There is no experience in the use of activated charcoal after ingestion of anthrax contaminated food. Activated charcoal might be of use after recent ingestion. 2) CHARCOAL ADMINISTRATION a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
3) CHARCOAL DOSE a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005). 1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
b) ADVERSE EFFECTS/CONTRAINDICATIONS 1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
6.5.3) TREATMENT
A) SUPPORT 1) MANAGEMENT OF SEVERE TOXICITY a) In patients with impending compromised airway or respiratory failure, support airway with endotracheal intubation and mechanical ventilation. Maintain ventilation and oxygenation and evaluate with frequent arterial blood gas or pulse oximetry monitoring. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Monitor serum electrolytes and fluid status and correct appropriately.
b) Early diagnosis and treatment before onset of sepsis is essential. Refer to treatment recommendations in INHALATION EXPOSURE SECTION for complete antibiotic treatment recommendations.
B) POST-EXPOSURE PROPHYLAXIS 1) Refer to INHALATION EXPOSURE SECTION for complete antibiotic postexposure prophylaxis treatment recommendations.
C) MONITORING OF PATIENT 1) Obtain CBC, electrolytes, BUN and creatinine, and cultures of blood, CSF, ascites fluid or pleural effusions as clinically indicated.
2) Monitor vital signs.
3) Anthraxin skin testing appears to be valuable for early diagnosis of acute anthrax, but is not widely available.
4) Cultures of infected blisters in cutaneous anthrax can be identified and diagnostic.
5) Chest x-ray may be a valuable diagnostic tool for respiratory forms of anthrax. Chest x-ray in these patients is characterized by a widened mediastinum and pleural effusions.
6) Cranial CT may be of value in suspected cases of anthrax meningoencephalitis.
7) Enzyme-linked immunosorbent assay (ELISA) and electrophoretic immunotransblot test (EITB, Western blot) may be valuable serologic diagnostic tests.
D) FLUID/ELECTROLYTE BALANCE REGULATION 1) Careful monitoring of electrolytes and proper fluid replacement is essential in malignant edema and intestinal and septicemic anthrax. Fluid and electrolyte replacement may approach those required in treatment of cholera. Fluid replacement is important shortly after starting antibiotic therapy and subsequent toxin release (LaForce, 1994). Assess clinical status to determine magnitude of dehydration.
2) MODERATE TO SEVERE DEHYDRATION (and normal renal function): Rehydrate over 30 to 45 minutes with 1 to 2 liters normal saline or lactated Ringers solution. Repeat a bolus (0.5 to 1 L) over 30 to 45 minutes if response is poor. In children begin with 10 to 20 milliliters/kilogram of normal saline or lactated Ringers solution.
3) With rapidly continuing losses, suspected cardiac or renal dysfunction, or inability to stabilize patient, central venous pressure or pulmonary wedge pressure may need to be monitored.
4) Following stabilization of vital signs and other parameters of severe dehydration, maintenance and deficit fluids can be replaced by a combination of 0.5NS, 0.25NS, and D5W at a rate to maintain normal vital signs and urine output. This assumes that most patients will be dehydrated but not hyponatremic.
E) AIRWAY MANAGEMENT 1) In the event of airway compromise, supportive measures including endotracheal intubation and mechanical ventilation may be necessary.
F) HYPOTENSIVE EPISODE 1) SUMMARY a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
2) DOPAMINE a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
3) NOREPINEPHRINE a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005). b) DOSE 1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
G) ACUTE LUNG INJURY 1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases. 2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011). a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011). 4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998). 5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995). 6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005). 7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015). H) ANTHRAX VACCINATION 1) Refer to INHALATION EXPOSURE SECTION for complete anthrax vaccination recommendations.
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6.7.2) TREATMENT
A) SUPPORT 1) MANAGEMENT OF SEVERE TOXICITY a) In patients with impending compromised airway or respiratory failure, support airway with endotracheal intubation and mechanical ventilation. Maintain ventilation and oxygenation and evaluate with frequent arterial blood gas or pulse oximetry monitoring. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Monitor serum electrolytes and fluid status and correct appropriately. Begin IV antibiotic treatment as soon as possible.
2) Hospitalized patients should be kept in strict isolation (LaForce, 1994). B) MONITORING OF PATIENT 1) Obtain CBC, electrolytes, BUN and creatinine, and cultures of blood, CSF, ascites fluid or pleural effusions as clinically indicated.
2) Monitor vital signs.
3) Anthraxin skin testing appears to be valuable for early diagnosis of acute anthrax, but is not widely available.
4) Cultures of infected blisters in cutaneous anthrax can be identified and diagnostic.
5) Chest x-ray may be a valuable diagnostic tool for respiratory forms of anthrax. Chest x-ray in these patients is characterized by a widened mediastinum and pleural effusions.
6) Cranial CT may be of value in suspected cases of anthrax meningoencephalitis.
7) Enzyme-linked immunosorbent assay (ELISA) and electrophoretic immunotransblot test (EITB, Western blot) may be valuable serologic diagnostic tests.
8) Monitor for development of bacteremia, septic shock, metastatic infection (e.g., meningitis which may occur in up to 50% of patients). Death usually occurs within 24 to 36 hours of metastatic infection (Franz et al, 1997).
C) AIRWAY MANAGEMENT 1) Airway management is indicated for increasing tracheal edema in patients with inhalational or oropharyngeal anthrax or edematous cutaneous anthrax. Endotracheal intubation and assisted mechanical ventilation with 100% oxygen may be required for treatment of respiratory depression.
D) ANTIBIOTIC THERAPY 1) SUMMARY: Begin IV antibiotic treatment as soon as possible. The antibiotic regimen of choice for inhalation, gastrointestinal, oropharyngeal, and severe cutaneous anthrax with systemic involvement, is combination therapy. If meningitis is suspected, the combination should include at least 3 drugs; one from each group. If meningitis is NOT suspected, combination therapy should include at least 2 drugs: one drug from either group 1 or 2 plus one drug from group 3. Duration of therapy is at least 2 weeks or until the patient is clinically stable, whichever is longer (Hendricks et al, 2014; Bradley et al, 2014). 2) GROUP 1 AGENTS (FLUOROQUINOLONES) a) CIPROFLOXACIN (FIRST LINE AGENT) 1) ADULT DOSE: 400 mg IV every 8 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older): 30 mg/kg/day IV divided every 8 hours (not to exceed 400 mg/dose) (Bradley et al, 2014).
3) PREGNANT WOMEN: At least one antibiotic that can cross the placenta (ie, ciprofloxacin, levofloxacin, meropenem, ampicillin, penicillin, clindamycin, rifampin) is recommended to be administered to pregnant patients with anthrax; however, ciprofloxacin is the preferred agent (Meaney-Delman et al, 2014).
b) LEVOFLOXACIN 1) ADULT DOSE: 750 mg IV every 24 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older, less than 50 kg): If meningitis is NOT suspected: 20 mg/kg/day IV divided every 12 hours, not to exceed 250 mg/dose. If meningitis IS suspected/confirmed: 16 mg/kg/day IV divided every 12 hours, not to exceed 250 mg/dose; (50 kg or more): 500 mg IV every 24 hours (Bradley et al, 2014).
c) MOXIFLOXACIN 1) ADULT DOSE: 400 mg IV every 24 hours (Hendricks et al, 2014). 2) PEDIATRIC DOSE (Bradley et al, 2014): 1) 3 month to less than 2 years: 12 mg/kg/day IV divided every 12 hours, not to exceed 200 mg/dose
2) 2 to 5 years: 10 mg/kg/day IV divided every 12 hours, not to exceed 200 mg/dose
3) 6 to 11 years: 8 mg/kg/day IV divided every 12 hours, not to exceed 200 mg/dose
4) 12 to 17 years, less than 45 kg: 8 mg/kg/day divided every 12 hours, not to exceed 200 mg/dose
5) 12 to 17 years, 45 kg or more: 400 mg IV once daily
3) GROUP 2 AGENTS (NON-FLUOROQUINOLONE BACTERICIDAL AGENTS) a) MEROPENEM (FIRST LINE AGENT) 1) ADULT DOSE: 2 g IV every 8 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older): If meningitis is NOT suspected: 60 mg/kg/day IV divided every 8 hours (not to exceed 2 g/dose). If meningitis IS suspected/confirmed: 120 mg/kg/day IV every 8 hours (not to exceed 2 g/dose) (Bradley et al, 2014).
b) IMIPENEM 1) ADULT DOSE: 1 g IV every 6 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older): 100 mg/kg/day IV divided every 6 hours (not to exceed 1 g/dose) (Bradley et al, 2014).
c) DORIPENEM 1) ADULT DOSE: 500 mg IV every 8 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older): 120 mg/kg/day IV divided every 8 hours (not to exceed 1 g/dose) (Bradley et al, 2014).
d) VANCOMYCIN 1) ADULT DOSE: 60 mg/kg/day IV divided every 8 hours (maintain serum trough concentrations of 15 to 20 mcg/mL) (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older): 60 mg/kg/day IV divided every 8 hours (Bradley et al, 2014).
e) PENICILLIN G 1) ADULT DOSE: 4 million units IV every 4 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older): 400,000 units/kg/day IV divided every 4 hours (not to exceed 4 million units/dose) (Bradley et al, 2014).
f) AMPICILLIN 1) ADULT DOSE: 3 g IV every 6 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older): If meningitis is NOT suspected, 200 mg/kg/day IV divided every 6 hours (not to exceed 3 g/dose). If meningitis IS suspected/confirmed: 400 mg/kg/day IV divided every 6 hours (not to exceed 3 g/dose) (Bradley et al, 2014).
4) GROUP 3 AGENTS (PROTEIN SYNTHESIS INHIBITORS) a) LINEZOLID (FIRST LINE AGENT) 1) ADULT DOSE: 600 mg IV every 12 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (less than 12 years): 30 mg/kg/day IV divided every 8 hours (not to exceed 600 mg/dose); (12 years or older): 30 mg/kg/day IV divided every 12 hours (not to exceed 600 mg/dose) (Bradley et al, 2014).
b) CLINDAMYCIN (FIRST LINE AGENT IF MENINGITIS IS NOT SUSPECTED) 1) ADULT DOSE: 900 mg IV every 8 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older): 40 mg/kg/day IV divided every 8 hours (not to exceed 900 mg/dose) (Bradley et al, 2014).
c) RIFAMPIN 1) ADULT DOSE: 600 mg IV every 12 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month of age or greater): 20 mg/kg/day IV divided every 12 hours (not to exceed 300 mg/dose) (Bradley et al, 2014).
d) CHLORAMPHENICOL (IF MENINGITIS IS SUSPECTED/CONFIRMED AND OTHER OPTIONS ARE NOT AVAILABLE) 1) ADULT DOSE: 1 g IV every 6 to 8 hours (Hendricks et al, 2014).
2) PEDIATRIC DOSE (1 month and older): 100 mg/kg/day IV divided every 6 hours (Bradley et al, 2014).
E) MONOCLONAL ANTIBODY 1) RAXIBACUMAB a) INDICATION 1) In combination with antibiotic therapy, raxibacumab is indicated to treat inhalational anthrax due to Bacillus anthracis in adult and pediatric patients. It can also be used as an alternative agent for prophylaxis of inhalational anthrax when other therapies are not available (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
2) Raxibacumab's efficacy is solely based on using raxibacumab in treating inhalational anthrax in animal model efficacy studies (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
b) MECHANISM OF ACTION 1) Raxibacumab is a monoclonal antibody that binds to the protective antigen (PA) of Bacillus anthracis. This inhibits binding of PA to its cellular receptors, and prevents the entry of anthrax lethal factor and edema factor into the cell. It does not cross the blood-brain barrier and cannot treat or prevent meningitis, and therefore must be given in conjunction with appropriate antibiotic therapy (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
c) DOSE 1) ADULT a) Given in combination with antibiotic therapy, the recommended dose of raxibacumab for the treatment of inhalational anthrax due to Bacillus anthracis is a single dose of 40 mg/kg IV, diluted to a final volume of 250 mL with 0.9% sodium chloride and infused over 2 hours and 15 minutes (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
b) Premedication with diphenhydramine 25 to 50 mg (oral or IV) 1 hour prior to raxibacumab administration is recommended to reduce the risk of infusion reactions (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
2) CHILD a) GREATER THAN 50 KG: Given in combination with antibiotic therapy, the recommended dose of raxibacumab for the treatment of inhalational anthrax due to Bacillus anthracis is a single dose of 40 mg/kg IV, diluted to a final volume of 250 mL with 0.9% sodium chloride and infused over 2 hours and 15 minutes (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
b) GREATER THAN 15 KG TO 50 KG: Given in combination with antibiotic therapy, the recommended dose of raxibacumab for the treatment of inhalational anthrax due to Bacillus anthracis is a single dose of 60 mg/kg IV, diluted to a final volume of 100 mL or 250 mL, depending on weight (see table below), with 0.9% sodium chloride and infused over 2 hours and 15 minutes (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
c) 15 KG OR LESS: Given in combination with antibiotic therapy, the recommended dose of raxibacumab for the treatment of inhalational anthrax due to Bacillus anthracis is a single dose of 80 mg/kg IV, diluted to a final volume in the range of 7 to 100 mL, depending on weight (see table below) with either 0.45% or 0.9% sodium chloride and infused over 2 hours and 15 minutes (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
d) Premedication with diphenhydramine 25 to 50 mg (oral or IV) 1 hour prior to raxibacumab administration is recommended to reduce the risk of infusion reactions (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
3) PREPARATION a) Based on body weight and dose, the total volume infused and the type of diluent used is as follows (Prod Info RAXIBACUMAB intravenous injection liquid, 2012): 4) ADMINISTRATION a) Administer via IV infusion at a rate based on the dose, as described in the following table (Prod Info RAXIBACUMAB intravenous injection liquid, 2012): 2) OBILTOXAXIMAB a) INDICATION 1) In combination with antibiotic therapy, obiltoxaximab is indicated to treat inhalational anthrax due to Bacillus anthracis in adult and pediatric patients. It can also be used as an alternative agent for prophylaxis of inhalational anthrax when other therapies are not available (Prod Info ANTHIM(R) intravenous injection, 2016).
2) Obiltoxaximab's efficacy is solely based on using obiltoxaximab in treating inhalational anthrax in animal model efficacy studies (Prod Info ANTHIM(R) intravenous injection, 2016).
b) MECHANISM OF ACTION 1) Obiltoxaximab is a monoclonal antibody that binds to the protective antigen (PA) of Bacillus anthracis. This inhibits binding of PA to its cellular receptors, and prevents the entry of anthrax lethal factor and edema factor into the cell. It does not cross the blood-brain barrier and cannot treat or prevent meningitis, and therefore must be given in conjunction with appropriate antibiotic therapy (Prod Info ANTHIM(R) intravenous injection, 2016).
c) DOSE 1) ADULT a) Given in combination with antibiotic therapy, the recommended dose of obiltoxaximab for the treatment of inhalational anthrax due to Bacillus anthracis is a single dose of 16 mg/kg IV, diluted to a final volume of 250 mL with 0.9% sodium chloride and infused over 90 minutes (Prod Info ANTHIM(R) intravenous injection, 2016).
b) Premedication with oral or IV diphenhydramine prior to obiltoxaximab administration is recommended to reduce the risk of infusion reactions (Prod Info ANTHIM(R) intravenous injection, 2016).
2) CHILD a) GREATER THAN 40 KG: Given in combination with antibiotic therapy, the recommended dose of obiltoxaximab for the treatment of inhalational anthrax due to Bacillus anthracis is a single dose of 16 mg/kg IV, diluted to a final volume of 250 mL with 0.9% sodium chloride and infused over 90 minutes (Prod Info ANTHIM(R) intravenous injection, 2016).
b) GREATER THAN 15 KG TO 40 KG: Given in combination with antibiotic therapy, the recommended dose of obiltoxaximab for the treatment of inhalational anthrax due to Bacillus anthracis is a single dose of 24 mg/kg IV, diluted to a final volume of 100 mL or 250 mL, depending on weight (see table below), with 0.9% sodium chloride and infused over 90 minutes (Prod Info ANTHIM(R) intravenous injection, 2016).
c) 15 KG OR LESS: Given in combination with antibiotic therapy, the recommended dose of obiltoxaximab for the treatment of inhalational anthrax due to Bacillus anthracis is a single dose of 32 mg/kg IV, diluted to a final volume in the range of 7 to 100 mL, depending on weight (see table below) with 0.9% sodium chloride and infused over 90 minutes (Prod Info ANTHIM(R) intravenous injection, 2016).
d) Premedication with oral or IV diphenhydramine prior to obiltoxaximab administration is recommended to reduce the risk of infusion reactions (Prod Info ANTHIM(R) intravenous injection, 2016).
3) PREPARATION AND ADMINISTRATION a) The following table contains obiltoxaximab dose, total infusion volume, and infusion rate by body weight (Prod Info ANTHIM(R) intravenous injection, 2016): F) ANTHRAX IMMUNE GLOBULIN 1) SUMMARY: Anthrax immune globulin is indicated, in combination with antibiotic therapy, for the treatment of inhalational anthrax in adult and pediatric patients. Effectiveness is solely based on animal efficacy studies (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015). 2) DOSE a) ADULT (17 YEARS AND OLDER): The starting dose is 420 units (7 vials) administered via IV infusion. Depending on the severity of symptoms and responsiveness of the patient, the initial dose may be increased to 840 units (14 vials). The starting infusion rate for the first 30 minutes is 0.5 mL/min, and increasing incrementally, every 30 minutes if tolerated, by 1 mL/min, up to a MAX infusion rate of 2 mL/min (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015). 1) Dose may be repeated in patients with substantial hemorrhage or who have significant compartmental fluid losses, and in patients with impaired or delayed immune response (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015).
b) CHILDREN (16 YEARS AND YOUNGER): The starting dose is 1 to 7 vials (60 to 420 units), depending on patient's weight, administered as an IV infusion, with a starting infusion rate of 0.01 mL/kg/min (not to exceed the adult rate of 0.5 mL/min). The rate may be increased incrementally every 30 minutes, if tolerated, by 0.02 mL/kg/min, up to a MAX infusion rate of 0.04 mL/kg/min (not to exceed the adult MAX rate of 2 mL/min) (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015): 1) WEIGHT LESS THAN 10 KG: 1 vial per dose
2) 10 KG TO LESS THAN 18 KG: 2 vials per dose
3) 18 KG TO LESS THAN 25 KG: 3 vials per dose
4) 25 KG TO LESS THAN 35 KG: 4 vials per dose
5) 35 KG TO LESS THAN 50 KG: 5 vials per dose
6) 50 KG TO LESS THAN 60 KG: 6 vials per dose
7) 60 KG OR GREATER: 7 vials per dose
8) Depending on the severity of symptoms and responsiveness of the patient, the dose may be doubled in patients who weigh greater than 5 kg (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015).
3) ADVERSE EFFECTS a) Safety data of anthrax immune globulin is based on healthy volunteers and 19 adult patients with anthrax who were treated with anthrax immune globulin under expanded access use (3 patients with inhalational anthrax, 1 patient with gastrointestinal anthrax, and 15 patients with anthrax secondary to injection of anthrax-contaminated heroin) (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015).
b) The most common adverse effects observed during clinical trials involving healthy volunteers, with an incidence rate of greater than 5%, were headache, infusion site reactions (ie, swelling and pain), nausea, and back pain. Eight of the 19 patients with anthrax experienced the following adverse effects within 72 hours of anthrax immune globulin infusion: acute respiratory distress syndrome (n=2), acute renal insufficiency/failure (n=4), pulmonary edema, pleural effusion, coagulopathy, hypotension, ascites, metabolic acidosis, hyperkalemia, edema/peripheral edema, and cardiac arrest/death (not otherwise specified, n=2) (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015).
c) There were 6 deaths reported among the anthrax patients, including the patient with inhalational anthrax. Three of the deaths were attributed to progression of the anthrax or co-morbidities. Causes of the other 3 deaths were not determined or not available at the time of this review (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015).
d) Thrombosis may occur with immune globulin products, including anthrax immune globulin. Risk factors may include hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, prolonged immobilization, indwelling vascular catheters, hyperviscosity, impaired cardiac output, and advanced age, although thrombosis may also occur in the absence of risk factors. In patients with risk factors, anthrax immune globulin should be administered at the minimum rate of infusion that is practicable, with adequate hydration to the patient prior to administration (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015).
4) LABORATORY INTERFERENCE: Falsely elevated blood glucose readings may occur with some point-of-care blood glucose testing systems (eg, glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase methods) due to the maltose that is contained within Anthrasil (R), anthrax immune globulin. It is suggested that diabetic patients receiving Anthrasil (R), only use testing systems that are glucose-specific (monitor and test strips) to monitor blood glucose levels (Prod Info ANTHRASIL(TM) intravenous injection solution, 2015). G) ANTHRAX VACCINATION 1) PRE-EXPOSURE VACCINATION a) Pre-exposure vaccination with anthrax vaccine adsorbed (AVA) is recommended for laboratory personnel involved in working with high concentrations of pure cultures of Bacillus anthracis spores, or with environmental samples associated with anthrax investigations, or in spore-contaminated areas or setting with high aerosol exposure. Pre-exposure vaccination is also recommended for military personnel according to department of defense guidelines, and for individuals involved in environmental investigations or remediation efforts (Centers for Disease Control and Prevention, 2009).
b) An anthrax licensed vaccine is available from Emergent BioDefense Operations Lansing LLC under the tradename, BioThrax(TM) (Prod Info BioThrax(R) intramuscular injection suspension, subcutaneous injection suspension, 2012; CDC, 2000; CDC, 1999; Franz et al, 1997). It may also be requested through the Centers for Disease Control. The licensed vaccine contains no dead or live bacteria.
c) DOSING: The recommended dose of the US vaccine (Anthrax Vaccine Adsorbed) for primary immunization is 0.5 mL intramuscularly at 0, 1, and 6 months, followed by 2 additional 0.5 mL injections at 12 and 18 months; thereafter, yearly booster doses (0.5 mL) are recommended to maintain immunity in those who remain at risk. Protection is conferred upon receipt of the full series (5 doses) of vaccinations. Subcutaneous administration may be used when medically indicated, such as in persons with coagulation disorders or in those receiving medications that affect coagulation. Dosing intervals are 0, 2, 4 weeks, and 6 months, with booster doses at 12 and 18 months, followed by yearly booster doses for patients who continue to remain at risk (Prod Info BioThrax(R) intramuscular injection suspension, subcutaneous injection suspension, 2012; Centers for Disease Control and Prevention, 2009).
2) POST-EXPOSURE PROPHYLAXIS a) Postexposure vaccine prophylaxis is recommended for all previously unvaccinated persons (including pregnant and nursing women) following exposure to aerosolized Bacillus anthracis species, whether exposure was naturally occurring, occupationally-related, or intentional. Postexposure vaccination is performed with an inactivated, cell-free anthrax vaccine and may be given in conjunction with chemoprophylaxis. Begin vaccination as soon as possible after exposure. Vaccine is administered subcutaneously in a series of three injections at a dose of 0.5 mL and repeated at 2 weeks and 4 weeks (Centers for Disease Control and Prevention, 2009; CDC, 2000; CDC, 1999; Franz et al, 1997; LaForce, 1994). The vaccine has not been evaluated for safety and efficacy in children, although based on experience with other inactivated vaccines, it is likely that the vaccine would be safe and effective (Inglesby et al, 2002). b) Vaccination alone after exposure is not effective. Antibiotic therapy with either oral ciprofloxacin 500 mg twice daily or doxycycline 100 mg twice daily should also be administered for 60 days. The duration of postexposure antibiotic therapy when used alone is also 60 days (Centers for Disease Control and Prevention, 2009; CDC, 2002; CDC, 2001; Inglesby et al, 2002a). c) For previously unvaccinated workers at risk for occupational exposure, postexposure vaccination guidelines should be followed along with a 60 day course of antibiotic therapy, then the licensed vaccination regimen should be followed at the 6-month dose. Individuals who are partially vaccinated at the time of exposure should also receive a 60-day course of postexposure antibiotic prophylaxis and should continue with the primary vaccination regimen (Hendricks et al, 2014; Centers for Disease Control and Prevention, 2009). d) Administration of vaccine during breast-feeding is not medically contraindicated (Modlin et al, 2001). e) Vaccine-resistant and antibiotic-resistant anthrax strains have been found to exist, and the potential exists for these strains to be used in a biological warfare attack (Nass, 1998). f) An experimental live, attenuated recombinant anthrax vaccine has shown promising protective effects in guinea pig experiments, but has not been used or approved in humans (Barnard & Friedlander, 1999). g) ADVERSE EFFECTS 1) In a survey of military personnel who had received anthrax vaccine, no patterns of unexpected local or systemic adverse events were identified (CDC, 2000a). Approximately 30% of vaccine recipients experience mild local reactions. One case of a delayed and life-threatening anaphylactoid reaction was reported 20 hours after the third dose of vaccine (Swanson-Biearman & Krenzelok, 2001).
2) Other adverse effects to anthrax vaccine that have been reported include: arthralgia, myalgia, arthritis, arthrosis, joint disease, flu syndrome, Guillain-Barre syndrome, myelitis and vasculitis (Geier & Geier, 2002).
3) Acute optic neuritis and eye pain were reported in 2 patients following anthrax booster vaccinations. One patient developed symptoms 1 month after vaccination and had excellent visual recovery following treatment with intravenous methylprednisolone. The other patient reported symptoms 2 weeks after vaccination and has required long-term immunosuppression to maintain his vision (Kerrison et al, 2002).
3) REPORTING: All confirmed and highly probable cases must be reported to local or state public health departments. H) POST-EXPOSURE PROPHYLAXIS 1) Patients exposed to aerosolized Bacillus anthracis spores require 60-day oral antibiotic prophylaxis. 2) CIPROFLOXACIN (FIRST LINE AGENT) a) ADULT DOSE: 500 mg orally every 12 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE (1 month and older): 30 mg/kg/day orally divided every 12 hours (not to exceed 500 mg/dose) (Bradley et al, 2014).
c) PREGNANT PATIENT: Ciprofloxacin is the preferred agent in pregnant women, with dosing the same as the adult dose (Meaney-Delman et al, 2014).
3) DOXYCYCLINE (FIRST LINE AGENT) a) ADULT DOSE: 100 mg orally every 12 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE (1 month and older, less than 45 kg): 4.4 mg/kg/day orally divided every 12 hours, not to exceed 100 mg/dose, (45 kg and more): 100 mg orally every 12 hours (Bradley et al, 2014).
c) TEETH STAINING: Prolonged doxycycline therapy (eg, up to 60 days), particularly in children less than 8-years-old, may result in permanent tooth discoloration (Bradley et al, 2014).
4) CLINDAMYCIN a) ADULT DOSE: 600 mg orally every 8 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE (1 month and older): 30 mg/kg/day orally divided every 8 hours (not to exceed 600 mg/dose) (Bradley et al, 2014).
5) LEVOFLOXACIN a) ADULT DOSE: 750 mg orally every 24 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE (1 month and older, less than 50 kg): 16 mg/kg/day orally divided every 12 hours (not to exceed 250 mg/dose); (50 kg and greater): 500 mg orally every 24 hours (Bradley et al, 2014).
6) MOXIFLOXACIN a) ADULT DOSE: 400 mg orally every 24 hours (Hendricks et al, 2014).
7) AMOXICILLIN a) ADULT DOSE: 1 g orally every 8 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE (1 month and older): 75 mg/kg/day orally divided every 8 hours (not to exceed 1 g/dose) (Bradley et al, 2014).
8) PENICILLIN VK a) ADULT DOSE: 500 mg orally every 6 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE (1 month and older): 50 to 75 mg/kg/day orally divided every 6 to 8 hours (Bradley et al, 2014).
I) FLUID/ELECTROLYTE BALANCE REGULATION 1) Monitor electrolytes and fluid status and correct appropriately. Fluid replacement is important shortly after starting antibiotic therapy and subsequent toxin release (LaForce, 1994). Assess clinical status to determine magnitude of dehydration.
J) HYPOTENSIVE EPISODE 1) SUMMARY a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
2) DOPAMINE a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
3) NOREPINEPHRINE a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005). b) DOSE 1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
K) ACUTE LUNG INJURY 1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases. 2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011). a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011). 4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998). 5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995). 6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005). 7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015). L) CORTICOSTEROID 1) Corticosteroids may reduce the morbidity and mortality of severe tracheal edema associated with inhalational anthrax (LaForce, 1994). Dexamethasone may be given in a dose of 0.5 mg/kg/day intravenously.
M) EXPERIMENTAL THERAPY 1) CHLOROQUINE: In one study, BALB/c mice challenged with anthrax lethal toxin (LeTx) were treated with chloroquine with doses similar to those used in human malaria treatment regimens. Chloroquine significantly increased survival and reduced tissue injury (as evaluated using histopathological examination of the spleen and by peripheral blood differential cell count ratios). The authors concluded that chloroquine may be combined with current antimicrobial treatment to optimize the management of patients; however, further studies are needed (Artenstein et al, 2004).
N) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate. |
6.9.1) DECONTAMINATION
A) DERMAL DECONTAMINATION 1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
B) CLOTHING 1) Bag soiled clothing or dressings in polyethylene until autoclaved or incinerated.
6.9.2) TREATMENT
A) SUPPORT 1) MANAGEMENT OF MILD TO MODERATE TOXICITY a) Begin oral antibiotic treatment if localized or uncomplicated cutaneous anthrax is suspected. Cutaneous lesion care includes cleansing and covering of the lesion(s). Excision of the lesions are contraindicated due to potential worsening of symptoms and spread of infection. Monitoring of serum electrolytes and fluid replacement is essential in malignant edema and resulting septicemia. Fluid replacement is important shortly after the start of antibiotics and subsequent toxin release. Cutaneous anthrax of the eyelids has led to corneal scarring from cicatricial ectropion. Usual treatment of corneal scarring and ophthalmologic consult may be required.
2) MANAGEMENT OF SEVERE TOXICITY a) In patients with impending compromised airway or respiratory failure, support airway with endotracheal intubation and mechanical ventilation. Maintain ventilation and oxygenation and evaluate with frequent arterial blood gas or pulse oximetry monitoring. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Monitor serum electrolytes and fluid status and correct appropriately. Begin IV antibiotic treatment as soon as possible.
b) Early diagnosis and treatment before onset of sepsis is essential. For severe cutaneous anthrax with systemic involvement, refer to treatment recommendations in INHALATION EXPOSURE SECTION for complete antibiotic treatment recommendations.
B) MONITORING OF PATIENT 1) Obtain CBC, electrolytes, BUN and creatinine, and cultures of blood, CSF, ascites fluid or pleural effusions as clinically indicated.
2) Monitor vital signs.
3) Anthraxin skin testing appears to be valuable for early diagnosis of acute anthrax, but is not widely available.
4) Cultures of infected blisters in cutaneous anthrax can be identified and diagnostic.
5) Cranial CT may be of value in suspected cases of anthrax meningoencephalitis.
6) Enzyme-linked immunosorbent assay (ELISA) and electrophoretic immunotransblot test (EITB, Western blot) may be valuable serologic diagnostic tests.
C) POST-EXPOSURE PROPHYLAXIS 1) Refer to INHALATION EXPOSURE SECTION for complete antibiotic postexposure prophylaxis treatment recommendations.
D) CUTANEOUS ANTHRAX 1) LOCALIZED/UNCOMPLICATED ANTHRAX: For cutaneous anthrax without systemic involvement, begin oral antibiotic therapy with one of the first line agents. If first-line therapy is not tolerated or unavailable, an alternative agent should be administered. Duration of therapy is 7 to 10 days for naturally-acquired anthrax and 60 days for bioterrorism-related cases (Hendricks et al, 2014). 2) CIPROFLOXACIN (FIRST LINE AGENT FOR ADULTS AND CHILDREN) a) ADULT DOSE: 500 mg orally every 12 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE (1 month and older): 30 mg/kg/day orally divided every 12 hours (not to exceed 500 mg/dose) (Bradley et al, 2014).
c) PREGNANT WOMEN: Ciprofloxacin is the preferred agent (Meaney-Delman et al, 2014).
3) DOXYCYCLINE (FIRST LINE AGENT FOR ADULTS ONLY) a) ADULT DOSE: 100 mg orally every 12 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE (1 month and older, less than 45 kg): 4.4 mg/kg/day orally divided every 12 hours, not to exceed 100 mg/dose, (45 kg or more): 100 mg orally every 12 hours (Bradley et al, 2014).
4) LEVOFLOXACIN (FIRST LINE AGENT FOR ADULTS ONLY) a) ADULT DOSE: 750 mg orally every 24 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE (1 month and older, less than 50 kg): 16 mg/kg/day orally divided every 12 hours, not to exceed 250 mg/dose, (50 kg or more): 500 mg orally every 24 hours (Bradley et al, 2014).
5) MOXIFLOXACIN (FIRST LINE AGENTS FOR ADULTS ONLY a) ADULT DOSE: 400 mg orally every 24 hours (Hendricks et al, 2014).
6) CLINDAMYCIN a) ADULT DOSE: 600 mg orally every 8 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE: 30 mg/kg/day orally divided every 8 hours (not to exceed 600 mg/dose) (Bradley et al, 2014).
7) AMOXICILLIN a) ADULT DOSE: 1 g orally every 8 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE: 75 mg/kg/day orally every 8 hours (not to exceed 1 g/dose) (Bradley et al, 2014).
8) PENICILLIN VK a) ADULT DOSE: 500 mg orally every 6 hours (Hendricks et al, 2014).
b) PEDIATRIC DOSE: 50 to 75 mg/kg/day orally divided every 6 to 8 hours (Bradley et al, 2014).
E) FLUID/ELECTROLYTE BALANCE REGULATION 1) Careful monitoring of electrolytes and proper fluid replacement is essential in malignant edema and intestinal and septicemic anthrax. Fluid and electrolyte replacement may approach those required in treatment of cholera. Fluid replacement is important shortly after starting antibiotic therapy and subsequent toxin release (LaForce, 1994). Assess clinical status to determine magnitude of dehydration.
2) MODERATE TO SEVERE DEHYDRATION (and normal renal function): Rehydrate over 30 to 45 minutes with 1 to 2 liters normal saline or lactated Ringers solution. Repeat a bolus (0.5 to 1 L) over 30 to 45 minutes if response is poor. In children begin with 10 to 20 milliliters/kilogram of normal saline or lactated Ringers solution.
3) With rapidly continuing losses, suspected cardiac or renal dysfunction, or inability to stabilize patient, central venous pressure or pulmonary wedge pressure may need to be monitored.
4) Following stabilization of vital signs and other parameters of severe dehydration, maintenance and deficit fluids can be replaced by a combination of 0.5NS, 0.25NS, and D5W at a rate to maintain normal vital signs and urine output. This assumes that most patients will be dehydrated but not hyponatremic.
F) AIRWAY MANAGEMENT 1) In cases of airway compromise, supportive measures including endotracheal intubation and mechanical ventilation may be necessary.
G) WOUND CARE 1) Patients should be isolated with drainage/secretion precautions observed until antibiotic therapy is completed and lesions have healed; wear gloves or gowns when in contact with infectious material.
2) Cutaneous lesion care includes cleansing and covering of the lesion. Bag the soiled dressings in polyethylene until autoclaved or burned to destroy spores. Excision of the lesions is contraindicated due to potential worsening of symptoms and spread of infection (LaForce, 1994).
3) Eschar formation at the lesion site has been reported. Following antibiotic therapy, removal of the eschar has been accomplished, with a split-thickness skin graft applied to the area after eschar removal (Wylock et al, 1983).
H) CORTICOSTEROID 1) Corticosteroids may reduce morbidity and mortality of severe cutaneous anthrax. Dexamethasone may be given in a dose of 0.5 mg/kg/day IV (LaForce, 1994).
I) HYPOTENSIVE EPISODE 1) SUMMARY a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
2) DOPAMINE a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
3) NOREPINEPHRINE a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005). b) DOSE 1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
J) ACUTE LUNG INJURY 1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases. 2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011). a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011). 4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998). 5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995). 6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005). 7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015). K) ANTHRAX VACCINATION 1) Refer to INHALATION EXPOSURE SECTION for complete anthrax vaccination recommendations.
L) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate. |