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Introduction

  1. Pharmacology. Botulism antitoxin contains equine polyclonal antibody fragments directed against the botulinum neurotoxins produced by the various strains of Clostridium botulinum. It provides passive immunization by binding to free circulating botulinum neurotoxins.
    1. Botulism antitoxin heptavalent (BAT) contains equine-derived antibody fragments that bind botulinum neurotoxin serotypes A, B, C, D, E, F, and G. It is composed of F(ab')2 and F(ab')2-related immunoglobulin. The pentavalent botulism toxoid vaccine for laboratory workers has been discontinued and is no longer recommended by the CDC.
    2. A human-derived botulism immune globulin (IgG antibodies), BabyBIG, is approved for the treatment of infant botulism caused by toxins A and B and has demonstrated significant reduction in the length of hospitalization associated with infant botulism.
    3. The antitoxins bind and inactivate only freely circulating botulinum neurotoxins; they do not remove toxin that is already bound to nerve terminals. Because antitoxin will not reverse established paralysis once it occurs, it must be administered before paralysis sets in. Treatment within 24 hours of the onset of symptoms may shorten the course of intoxication and prevent progression to total paralysis.
  2. Indications
    1. BAT heptavalent is indicated for the treatment of symptomatic botulism (see Botulism) following documented or suspected exposure to botulinum neurotoxin serotypes A, B, C, D, E, F, or G.
    2. Human-derived BabyBIG immune globulins used for the treatment of infant botulism.
  3. Contraindications
    1. Equine-derived antibodies (BAT). No absolute contraindications. Administration of this product to a patient with known or suspected hypersensitivity to botulinum antitoxin or horse serum requires extreme caution and skin sensitivity testing (see dosage section).
    2. Human-derived immune globulin. BabyBIG should not be given to patients with a prior history of severe reaction to human immunoglobulin products. BabyBIG contains trace amounts of IgA. Individuals with selective IgA deficiency may develop anaphylactic reactions to subsequently administered blood products with IgA.
  4. Adverse effects
    1. Equine-derived antibodies. Immediate hypersensitivity reactions (anaphylactic shock, angioedema, urticaria) resulting from the equine source of antibodies. Prepare for monitoring and management of allergic reactions (see dosage section). Monitor for delayed allergic reactions (serum sickness), which may occur up to 10 to 21 days after administration. Discontinue infusion and administer appropriate medical care if infusion reactions occur.
    2. Human-derived immune globulin. Mild transient erythematous rashes of the face and trunk have been reported commonly. Infusion rate-related reactions ranging from mild flushing to severe anaphylaxis may occur. Flulike symptoms similar to those seen with the use of other immune globulin intravenous products have been observed.
    3. Use in pregnancy. There are no data on teratogenicity. Anaphylactic reaction resulting in shock or hypoxemia in the mother could conceivably affect the fetus adversely.
  5. Drug or laboratory interactions. BAT heptavalent contains maltose and can produce falsely elevated glucose readings with some testing systems; use of glucose-specific testing is advised. Human-derived immune globulin (BabyBIG) preparations contain antibodies that may interfere with the immune response to live vaccines such as those for polio, measles, mumps, and rubella. Vaccination with live virus vaccines should be delayed until approximately 3 months or more after administration of BabyBIG.
  6. Dosage and method of administration
    1. BAT heptavalent. To obtain BAT heptavalent, healthcare providers should first contact their local or state health department for reporting and to facilitate access to the antitoxin. Additional emergency consultation is available 24/7 from the botulism duty officer via the CDC Emergency Operations Center at 1-770-488-7100. Consider skin sensitivity testing for patients with suspected horse serum sensitivity (see VI.A.4. below). In patients at risk for hypersensitivity reactions, begin BAT administration at lowest rate achievable. Otherwise, administer by slow IV infusion after 1:10 dilution in normal saline as follows:
      1. Adult. Total dose is 1 vial (10-22 mL depending on the lot number, but all contain the equivalent amount of antibodies per vial). Start at a rate of 0.5 mL/min for 30 minutes. If tolerating infusion, double the rate every 30 minutes to a maximum of 2 mL/min.
      2. Pediatric (1 year to <17 years). Give 20-100% of the adult dose by weight (see below). Start at 0.01 mL/kg/min not to exceed 0.5 mL/min for 30 minutes. If tolerating infusion, increase by 0.01 mL/kg/min every 30 minutes to a maximum of 0.03 mL/kg/min, not to exceed 2 mL/min. Percentage of adult dose by weight: 10-14 kg = 20%, 15-19 kg = 30%, 20-24 kg = 40%, 25-29 kg = 50%, 30-34 kg = 60%, 35-39 kg = 65%, 40-44 kg = 70%, 45-49 kg = 75%, 50-54 kg = 80%, ≥55 kg = 100%.
      3. Infant (<1 year). Give 10% of the adult dose regardless of body weight. Start at 0.01 mL/kg/min for 30 minutes. If tolerating infusion, increase to 0.01 mL/kg/min every 30 minutes to a maximum of 0.03 mL/kg/min.
      4. Skin test for patients at risk of anaphylaxis due to suspected horse serum sensitivity. Dilute BAT in saline (1:1,000) and inject 0.02 mL intradermally on the volar surface of the forearm. Perform a concurrent positive (histamine) and negative (saline) control test. A positive test is a wheal with surrounding erythema at least 3 mm larger than the control test; read at 15-20 minutes. The histamine control must be positive for valid interpretation. If a hypersensitivity reaction occurs, discontinue BAT administration immediately, maintain airway, treat hypotension with IV fluids, and administer epinephrine and diphenhydramine depending on the severity of the reaction (see Table I-17).
    2. BabyBIG. To obtain or determine the availability of BabyBIG for suspected infant botulism, contact the Infant Botulism Treatment and Prevention Program (IBTPP) at 1-510-231-7600. More information is available at www.infantbotulism.org. In cases of infant botulism, the recommended dosage is 1 mL/kg (50 mg/kg) as a single intravenous infusion as soon as a clinical diagnosis of infant botulism is made. BabyBIG should be administered at 0.5 mL/kg/h (25 mg/kg/h). The rate may be increased to 1.0 mL/kg/h (50 mg/kg/h) if no untoward reaction occurs 15 minutes after the initial infusion rate. The half-life of injected BabyBIG is approximately 28 days in infants, and a single intravenous infusion is expected to provide a protective level of neutralizing antibodies for 6 months.