ToxCard: Botulism

Authors: Courtney Owens, MD (EM Resident Physician, Carolinas Medical Center, Charlotte, NC) and Kathryn T Kopec, DO (@KopecToxEM, EM Attending Physician; Medical Toxicologist, Carolinas Medical Center, Charlotte, NC) // Reviewed by: James Dazhe Cao, MD (@JamesCaoMD, Associate Professor of EM, Medical Toxicology, UTSW / Parkland Memorial Hospital); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)


A 32-year-old man with history of intravenous drug use presents to the emergency department complaining of generalized weakness and double vision which has progressively worsened over the past two days. Vital signs on arrival are temperature 100.2 F, blood pressure 126/82 mmHg, heart rate 101 beats/min, respiratory rate 20 breaths/min, and oxygen saturation of 100% on room air. His exam is remarkable for an erythematous wound on the left antecubital fossa that is draining purulent material, diffuse extremity weakness worse in the bilateral upper extremities, and bilateral cranial nerve VI palsy.


  1. What is the diagnosis?
  2. What are the different types of botulism?
  3. How is botulism diagnosed and treated?


  • Botulism is a rare but potentially life-threatening syndrome caused by the Clostridium botulinum.
  • C. botulism is a gram-positive, obligate anaerobic, rod-shaped, spore-forming bacterium that is commonly found in soil, river water and seawater. It has also been isolated on surfaces of foods such as vegetables, fruits, and seafood.1
  • The bacteria reproduces in oxygen-poor environments and secretes the botulism neurotoxin, which exerts its effects by binding to pre-synaptic nerve terminals and inhibiting the release of acetylcholine. This prevents acetylcholine from activating post-synaptic muscarinic and nicotinic receptors, both involved in parasympathetic nervous system function.2
  • The botulism neurotoxin is one of the most lethal toxins known, meaning that it can cause high mortality with an extremely small dose.3,4

Types of Botulism:

Foodborne Botulism5

  • Most common form of botulism worldwide.
  • Occurs when C. botulism produces botulism neurotoxin prior to consumption of food.
  • Highest risk foods are:
    • Processed or stored in conditions with anaerobic environment
    • pH > 4.6
    • Low salt and sugar content
    • Temperature 40-113 F such as in home-canned foods
  • Most commonly presents with gastrointestinal symptoms of nausea, vomiting, and diarrhea that either precede or accompany neurologic symptoms.


Infant/Adult Intestinal Toxemia Botulism6

  • Occurs when C. botulism spores colonize the gastrointestinal tract and produce botulism toxin in situ in infants (infant botulism) or in those over the age of one year (adult intestinal toxemia botulism).
  • Honey is often implicated as the source of spores in infant botulism.
  • Majority of cases of adult intestinal toxemia botulism occur in patients with previous bowel surgery, anatomic bowel anomalies, or those with recent antimicrobial usage.
  • Presentation is like foodborne botulism with gastrointestinal and neurologic symptoms.


Wound Botulism7,8

  • Occurs when a wound or necrotic tissue is infected with C. botulism spores, and toxin production is facilitated by the anaerobic environment of the necrotic tissue.
  • Highest risk amongst intravenous drug users who inject black tar heroin and/or engage in subcutaneous injection, known as skin popping.
  • Most commonly presents with fevers and leukocytosis due to likely polymicrobial wound infection as well as neurological symptoms.
    • Less commonly presents with gastrointestinal symptoms


Inhalation Botulism9-11

  • Occurs when aerosolized botulism toxin is inhaled into the lungs.
  • Results from intentional aerosol release (bioterrorism) or from laboratory/industrial accident.
  • Aerosolized botulism has been deployed unsuccessfully in warfare.
  • No specific case reports diagnosing this syndrome exist, but theorized to cause same neurologic symptoms as other types of botulism.


Iatrogenic Botulism12

  • Botulism toxin, colloquially known by a trade name “Botox,” is used for cosmetic purposes to reduce/eliminate wrinkles or as treatment for muscle dystonia, spasticity, neurogenic bladder, strabismus, and chronic migraines.
  • Iatrogenic botulism is rare, but cases have been reported with unlicensed formulations, concentrated formulations, and/or doses greater than manufacturer’s recommended maximum dose.

Clinical Presentation:

  • Botulism classically presents first with bulbar symptoms (diplopia, dysphagia, dysarthria, dysphonia) as cranial nerve presynaptic terminals are particularly susceptible to the botulism toxin.
  • Symptoms then usually progress to a symmetric, descending paralysis of the extremities.
  • Autonomic dysfunction including tachycardia, orthostatic hypotension, constipation, urinary retention, and dry mouth are also common.13
  • Suspect botulism in infants presenting with acute onset of a weak suck, ptosis, inactivity or constipation.6
  • Key physical exam findings that may suggest botulism:
    • Bilateral cranial nerve palsies
    • Decreased strength, worse in the upper extremities
  • Unilateral weakness or predominating sensory findings (loss of two-point discrimination, decreased proprioception) are not typical of botulism and require evaluation for alternative diagnoses.13


  • The diagnosis of botulism is mainly clinical based on a thorough history and physical examination.
  • Key historical features that might suggest botulism are:
    • Exposures to high-risk foods5
    • History of bowel surgery or recent antibiotic administration6
    • History of injection drug use or popping7
    • Recent iatrogenic exposure12
  • Diagnostic evaluation is challenging, as routine lab tests (CBC, BMP) and imaging (CT, MRI) have no characteristic abnormalities consistent with botulism.14
  • Electromyogram can help support the diagnosis, but findings are also nonspecific and nondiagnostic.13
  • Confirmation can be made with serum and stool assays for the botulism neurotoxin, stool microscopy for botulism spores, and wound cultures, however, these often takes several days to result.13


  • Symptomatic/supportive care
    • Airway support for respiratory compromise
    • Serial neurologic exams with attention to swallowing ability
    • Monitoring for autonomic dysfunction
    • Intravenous fluids
    • Wound debridement and antibiotics for wound botulism
      • Penicillin G – 3 million units IV every 4 hours or
      • Metronidazole – 500mg IV every 8 hours for penicillin allergic patients13
    • Antitoxin15,16
      • Types
        • Botulism Immune-Globin (BIG-IV) – patients less than one year old
        • Heptavalent Botulism Antitoxin (HBAT) – patients one year or older
      • Mechanism of Action
        • Binds botulism toxin in the blood and prevents its uptake into cells
        • Prevents progression of symptoms but does not reverse already present paralysis
      • Indications
        • FDA approved for patients with suspected exposure to botulism toxin
        • Shown to have better outcomes when given early in clinical course to prevent progression of symptoms
      • Adverse Effects
        • BIG-IV – skin rash, other serious reactions were not observed in clinical trials
        • HBAT – Type I hypersensitivity, infusion reactions, serum sickness
      • Administration
        • Once botulism is suspected, contact your state health department immediately to obtain a supply of antitoxin. If there is no answer, contact the CDC 24/7 at 770-488-7100.

Case Follow-up:

Upon further history, patient admits to recent black tar heroin injection. The patient was admitted for observation, wound debridement, and antibiotic administration. Heptavalent equine serum antitoxin was administered. Patient’s diplopia resolved, antecubital fossa wound healed, and he slowly regained upper extremity strength during his 10-day hospital course. Patient was discharged home with outpatient physical therapy and drug counseling.

Clinical Pearls:

  • Botulism is rare but life-threatening illness with symptoms including cranial nerve palsies, flaccid descending paralysis, autonomic dysfunction, and possible respiratory failure.
  • Botulism can result from foodborne, intestinal, wound, inhalation and iatrogenic exposure to the bacteria, spores, and/or its neurotoxin.
  • Diagnosis of botulism is largely clinical, as routine lab tests are nonspecific and confirmatory tests take days to result.
  • Treatment with antitoxin should be initiated as soon as there is clinical concern for botulism.


  1. World Health Organization. (2018, January 10). Botulism. World Health Organization. Retrieved September 12, 2021, from
  2. Dong, M., Masuyer, G., & Stenmark, P. (2019). Botulinum and Tetanus Neurotoxins. Annual Review of Biochemistry, 88(1), 811–837.
  3. Cenciarelli O, Riley PW, Baka A. Biosecurity Threat Posed by Botulinum Toxin. Toxins (Basel). 2019 Nov 20;11(12):681. doi: 10.3390/toxins11120681. PMID: 31757074; PMCID: PMC6950065.
  4. Janik E, Ceremuga M, Saluk-Bijak J, Bijak M. Biological Toxins as the Potential Tools for Bioterrorism. International Journal of Molecular Sciences. 2019; 20(5):1181.
  5. Lonati, D., Schicchi, A., Crevani, M., Buscaglia, E., Scaravaggi, G., Maida, F., Cirronis, M., Petrolini, V. M., & Locatelli, C. A. (2020). Foodborne Botulism: Clinical Diagnosis and Medical Treatment. Toxins, 12(8), 509.
  6. Harris, R. A., Anniballi, F., & Austin, J. W. (2020). Adult Intestinal Toxemia Botulism. Toxins, 12(2), 81.
  7. Peak, C. M., Rosen, H., Kamali, A., Poe, A., Shahkarami, M., Kimura, A. C., Jain, S., & McDonald, E. (2019). Wound Botulism Outbreak Among Persons Who Use Black Tar Heroin — San Diego County, California, 2017–2018. MMWR. Morbidity and Mortality Weekly Report, 67(5152), 1415–1418.
  8. Mechem CC, Walter FG. Wound botulism. Vet Hum Toxicol. 1994 Jun;36(3):233-7. PMID: 8066973.
  9. Botulinum Toxin (Botulism). (n.d.). Retrieved from
  10. Sugishima M. Aum Shinrikyo and the Japanese law on bioterrorism. Prehosp Disaster Med. 2003 Jul-Sep;18(3):179-83. doi: 10.1017/s1049023x00001023. PMID: 15141855.
  11. Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S, Osterholm MT, O’Toole T, Parker G, Perl TM, Russell PK, Swerdlow DL, Tonat K; Working Group on Civilian Biodefense. Botulinum toxin as a biological weapon: medical and public health management. JAMA. 2001 Feb 28;285(8):1059-70. doi: 10.1001/jama.285.8.1059. Erratum in: JAMA 2001 Apr 25;285(16):2081. PMID: 11209178.
  12. Rashid, E. A., El-Mahdy, N. M., Kharoub, H. S., Gouda, A. S., Elnabarawy, N. A., & Mégarbane, B. (2018). Iatrogenic Botulism Outbreak in Egypt due to a Counterfeit Botulinum Toxin A Preparation – A Descriptive Series of Patient Features and Outcome. Basic & Clinical Pharmacology & Toxicology, 123(5), 622-627. doi:10.1111/bcpt.13048
  13. Jeffery IA, Karim S. Botulism. [Updated 2021 Jul 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
  14. Centers for Disease Control and Prevention. (2006, October 6). CDC botulism. Centers for Disease Control and Prevention. Retrieved September 15, 2021, from
  15. Ni SA, Brady MF. Botulism Antitoxin. [Updated 2021 Jul 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
  16. Arnon, S. S., Schechter, R., Maslanka, S. E., Jewell, N. P., & Hatheway, C. L. (2006). Human Botulism Immune Globulin for the Treatment of Infant Botulism. New England Journal of Medicine, 354(5), 462–471.



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