Approach Considerations

High clinical suspcicion and clinical diagnosis with immediate antitoxin administration is the cornerstone of management, as laboratory tests are not helpful in the routine diagnosis of botulism.^[6]

A clinical criteria tool for early diagnosis has been developed for outbreak settings.^[27]

When botulism is suspected, consult public health officials immediately, request antitoxin, and if transferring to a higher level of care consider administering antitoxin before transfer.^[28] Full neurologic exam, brain imaging, lumbar puncture, electromyography, nerve conduction studies, and monitoring for anaphylaxis after antitoxin administration should be performed as applicable.

WBC counts and erythrocyte sedimentation rates are usually normal.^[29] Cerebrospinal fluid is also normal, except for occasional mild elevations in protein concentration.

Laboratory Studies

Laboratory confirmation of botulism requires either botulinum neurotoxin isolation or growth of a botulinum neurotoxin-producing Clostridium species (ie, C botulinum, C baratii, or C butyricum) in a stool, gastric aspirate, food, or wound culture.

Botulinum neurotoxin isolation requires intraperitoneal injection of the patient' serum, fluid extract of food or feces, etc. into pairs of mice with and without monovalent antitoxin followed by observation for development of clinical botulism.^{[6, 30]} This test was standardized in the 1970s and has limited sensitivity depending on the mode of toxin exposure. These assays are limited to specific state public health and CDC laboratories, where other assays may also be used to determine neurotoxin serotype. Patient samples must be collected prior to administration of antitoxin, but antitoxin administration must not be delayed in order to obtain samples (serum 5-15 mL, stool 10-20 g, gastric aspirate 5-10 mL, suspected food source 10-20 g or mL).^[1]

To send a specimen to the CDC for testing^[1]:

Call CDC consultant to discuss submission of specimens through local or state health department or state public health laboratory
Maintain the specimen at 36 ^oF-46 ^oF and ship with cold packs
Label package as required for Category B substances
Include completed CDC 50.34 with selected test order CDC-10132, Botulism Laboratory Confirmation and include phone and fax numbers for the state health department and hospital
Send package to: STAT (Attn: Botulism Lab, Unit 26) Centers for Disease Control and Prevention1600 Clifton Rd NE, Atlanta, GA 30329
Provde a tracking number to the CDC National Botulism Laboratory

C botulinum may be grown on selective media from samples of stool or foods. Note that the specimens for toxin analysis should be refrigerated (not frozen), but culture samples of C botulinum should not be refrigerated. Final results from culture for Clostridium species may take 2-3 weeks.

Because intestinal carriage is rare (and adult intestines typically do not allow for germination), identifying the organism or its toxin in vomitus, gastric fluid, or stool strongly suggests the diagnosis.^[4] Isolation of the organism from food without toxin is insufficient grounds for the diagnosis. Only experienced personnel who have been immunized with botulinum toxoid should handle the specimens. Because the toxin may enter the blood stream through the eye or via small breaks in the skin, precaution is warranted.

Wound cultures that grow C botulinum suggest of wound botulism.

Imaging Studies

Imaging studies are generally not useful in the diagnosis of botuli.^[31]

The only potential role for imaging studies (eg, CT scan, MRI) would be to rule out CNS pathology, such as intracranial mass lesions, cerebrovascular disease of the brainstem, or basilar artery stroke, in patients in whom the presentation is atypical or vague.

Other Tests

Results from nerve conduction studies are normal, and electromyography (EMG) reveals reduced amplitude of compound muscle action potentials.^{[7, 8]}

EMG may be useful in establishing a diagnosis of botulism, but the findings can be nonspecific and nondiagnostic, even in severe cases. Characteristic findings in patients with botulism include brief low-voltage compound motor-units, small M-wave amplitudes, and overly abundant action potentials. An incremental increase in M-wave amplitude with rapid repetitive nerve stimulation may help to localize the disorder to the neuromuscular junction. Single-fiber EMG may be a more useful and sensitive method for the rapid diagnosis of botulism intoxication, particularly in the absence of signs of general muscular weakness.

The results of the edrophonium chloride, or Tensilon, test for myasthenia gravis may be falsely positive in patients with botulism.^[32] If positive, it is typically much less dramatically positive than in patients with myasthenia gravis.

Treatment & Management

[Guideline] Rao AK, Sobel J, Chatham-Stephens K, Luquez C. Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021. MMWR Recomm Rep. 2021 May 7. 70 (2):1-30. [QxMD MEDLINE Link].
Potulska-Chromik A, Zakrzewska-Pniewska B, Szmidt-Sałkowska E, Lewandowski J, Siński M, Przyjałkowski W, et al. Long lasting dysautonomia due to botulinum toxin B poisoning: clinical-laboratory follow up and difficulties in initial diagnosis. BMC Res Notes. 2013 Oct 30. 6:438. [QxMD MEDLINE Link].
Chatham-Stephens K, Fleck-Derderian S, Johnson SD, Sobel J, Rao AK, Meaney-Delman D. Clinical Features of Foodborne and Wound Botulism: A Systematic Review of the Literature, 1932-2015. Clin Infect Dis. 2017 Dec 27. 66 (suppl_1):S11-S16. [QxMD MEDLINE Link]. [Full Text].
Sobel J. Botulism. Clin Infect Dis. 2005 Oct 15. 41 (8):1167-73. [QxMD MEDLINE Link].
Rao AK, Lin NH, Jackson KA, Mody RK, Griffin PM. Clinical Characteristics and Ancillary Test Results Among Patients With Botulism-United States, 2002-2015. Clin Infect Dis. 2017 Dec 27. 66 (suppl_1):S4-S10. [QxMD MEDLINE Link].
Sobel J. Diagnosis and treatment of botulism: a century later, clinical suspicion remains the cornerstone. Clin Infect Dis. 2009 Jun 15. 48 (12):1674-5. [QxMD MEDLINE Link].
Mallik A, Weir AI. Nerve conduction studies: essentials and pitfalls in practice. J Neurol Neurosurg Psychiatry. 2005 Jun. 76 Suppl 2 (Suppl 2):ii23-31. [QxMD MEDLINE Link].
Maselli RA, Bakshi N. AAEM case report 16. Botulism. American Association of Electrodiagnostic Medicine. Muscle Nerve. 2000 Jul. 23 (7):1137-44. [QxMD MEDLINE Link].
Botulinum. Stanek, SA; Saunders, D. USAMRIID’s MEDICAL MANAGEMENT OF BIOLOGICAL CASUALTIES HANDBOOK. 9th. FORT DETRICK FREDERICK, MARYLAND: USAMRIID; 2020 Sep. 149-54. [Full Text].
Infant Botulism. Centers for Disease Control and Prevention: Botulism in the United States, 1899-1996. Handbook for Epidemiologists, Clinicians, and Laboratory Workers. Centers for Disease Control and Prevention; 1998. 10. [Full Text].
Brunt J, van Vliet AH, van den Bos F, Carter AT, Peck MW. Diversity of the Germination Apparatus in Clostridium botulinum Groups I, II, III, and IV. Front Microbiol. 2016. 7:1702. [QxMD MEDLINE Link].
Caleo M, Restani L. Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and Pathology. Toxins (Basel). 2018 Apr 25. 10 (5):357-73; abstract ix. [QxMD MEDLINE Link].
Yuan J, Inami G, Mohle-Boetani J, Vugia DJ. Recurrent wound botulism among injection drug users in California. Clin Infect Dis. 2011 Apr 1. 52 (7):862-6. [QxMD MEDLINE Link].
Badell ML, Rimawi BH, Rao AK, Jamieson DJ, Rasmussen S, Meaney-Delman D. Botulism During Pregnancy and the Postpartum Period: A Systematic Review. Clin Infect Dis. 2017 Dec 27. 66 (suppl_1):S30-S37. [QxMD MEDLINE Link].
Werner SB, Passaro D, McGee J, Schechter R, Vugia DJ. Wound botulism in California, 1951-1998: recent epidemic in heroin injectors. Clin Infect Dis. 2000 Oct. 31 (4):1018-24. [QxMD MEDLINE Link].
Botulism: Epidemiological Overview for Clinicians. CDC.gov. Available at https://www.emergency.cdc.gov/agent/botulism/clinicians/epidemiology.asp#:~:text=An%20average%20of%20110%20cases,from%203%20to%2078%20years.. October 6, 2006; Accessed: November 26, 2022.
Kiyokawa M, Haning H. A Case Report of Wound Botulism - Rare Disease on the Rise with the Opioid Crisis. Hawaii J Health Soc Welf. 2021 Feb 1. 80 (4):88-91. [QxMD MEDLINE Link].
National Botulism Surveillance Summary, 2017. CDC.gov. Available at https://www.cdc.gov/botulism/surv/2017/index.html. January 15, 2020; Accessed: November 27, 2022.
Shaffer N, Wainwright RB, Middaugh JP, Tauxe RV. Botulism among Alaska Natives. The role of changing food preparation and consumption practices. West J Med. 1990 Oct. 153 (4):390-3. [QxMD MEDLINE Link].
Foodborne Botulism. Centers for Disease Control and Prevention: Botulism in the United States, 1899-1996. Handbook for Epidemiologists, Clinicians, and Laboratory Workers. Centers for Disease Control and Prevention; 1998. 8. [Full Text].
Lúquez C, Edwards L, Griffin C, Sobel J. Foodborne Botulism Outbreaks in the United States, 2001-2017. Front Microbiol. 2021. 12:713101. [QxMD MEDLINE Link].
Mechem CC, Walter FG. Wound botulism. Vet Hum Toxicol. 1994 Jun. 36 (3):233-7. [QxMD MEDLINE Link].
Chatham-Stephens K, Fleck-Derderian S, Johnson SD, Sobel J, Rao AK, Meaney-Delman D. Clinical Features of Foodborne and Wound Botulism: A Systematic Review of the Literature, 1932-2015. Clin Infect Dis. 2017 Dec 27. 66 (suppl_1):S11-S16. [QxMD MEDLINE Link].
MACLENNAN JD. The histotoxic clostridial infections of man. Bacteriol Rev. 1962 Jun. 26 (2 Pt 1-2):177-276. [QxMD MEDLINE Link].
Rasetti-Escargueil C, Lemichez E, Popoff MR. Toxemia in Human Naturally Acquired Botulism. Toxins (Basel). 2020 Nov 13. 12 (11):492-4. [QxMD MEDLINE Link].
Ghasemi M, Norouzi R, Salari M, Asadi B. Iatrogenic botulism after the therapeutic use of botulinum toxin-A: a case report and review of the literature. Clin Neuropharmacol. 2012 Sep-Oct. 35 (5):254-7. [QxMD MEDLINE Link].
Rao AK, Lin NH, Griese SE, Chatham-Stephens K, Badell ML, Sobel J. Clinical Criteria to Trigger Suspicion for Botulism: An Evidence-Based Tool to Facilitate Timely Recognition of Suspected Cases During Sporadic Events and Outbreaks. Clin Infect Dis. 2017 Dec 27. 66 (suppl_1):S38-S42. [QxMD MEDLINE Link].
Hick JL, Barbera JA, Kelen GD. Refining surge capacity: conventional, contingency, and crisis capacity. Disaster Med Public Health Prep. 2009 Jun. 3 (2 Suppl):S59-67. [QxMD MEDLINE Link].
Fokke C, van den Berg B, Drenthen J, Walgaard C, van Doorn PA, Jacobs BC. Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria. Brain. 2014 Jan. 137 (Pt 1):33-43. [QxMD MEDLINE Link].
Wheeler C, Inami G, Mohle-Boetani J, Vugia D. Sensitivity of mouse bioassay in clinical wound botulism. Clin Infect Dis. 2009 Jun 15. 48 (12):1669-73. [QxMD MEDLINE Link].
Rao AK, Lin NH, Jackson KA, Mody RK, Griffin PM. Clinical Characteristics and Ancillary Test Results Among Patients With Botulism-United States, 2002-2015. Clin Infect Dis. 2017 Dec 27. 66 (suppl_1):S4-S10. [QxMD MEDLINE Link].
Rao AK, Lin NH, Griese SE, Chatham-Stephens K, Badell ML, Sobel J. Clinical Criteria to Trigger Suspicion for Botulism: An Evidence-Based Tool to Facilitate Timely Recognition of Suspected Cases During Sporadic Events and Outbreaks. Clin Infect Dis. 2017 Dec 27. 66 (suppl_1):S38-S42. [QxMD MEDLINE Link].
U.S. Department of Health and Human Services. FDA approves first Botulism Antitoxin for use in neutralizing all seven known botulinum nerve toxin serotypes. FDA NEWS RELEASE. 2013 Mar 22. Available at http://wayback.archive-it.org/7993/20161022134538/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345128.htm.
Arnon SS, Schechter R, Maslanka SE, Jewell NP, Hatheway CL. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med. 2006 Feb 2. 354 (5):462-71. [QxMD MEDLINE Link].
Tacket CO, Shandera WX, Mann JM, Hargrett NT, Blake PA. Equine antitoxin use and other factors that predict outcome in type A foodborne botulism. Am J Med. 1984 May. 76 (5):794-8. [QxMD MEDLINE Link].
BAT® [Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) - (Equine)] [package insert]. Winnipeg, Canada: Cangene Corporation, a subsidiary of Emergent BioSolutions Inc. 2013. Available at [Full Text].
Sheth AN, Wiersma P, Atrubin D, Dubey V, Zink D, Skinner G, et al. International outbreak of severe botulism with prolonged toxemia caused by commercial carrot juice. Clin Infect Dis. 2008 Nov 15. 47 (10):1245-51. [QxMD MEDLINE Link].
Yu PA, Lin NH, Mahon BE, Sobel J, Yu Y, Mody RK, et al. Safety and Improved Clinical Outcomes in Patients Treated With New Equine-Derived Heptavalent Botulinum Antitoxin. Clin Infect Dis. 2017 Dec 27. 66 (suppl_1):S57-S64. [QxMD MEDLINE Link].
Lee JH, Lee SI, Chung CJ, Lee JH, Lee SC, Choi SR, et al. The synergistic effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade. Korean J Anesthesiol. 2013 Feb. 64 (2):143-51. [QxMD MEDLINE Link].
Lawn ND, Fletcher DD, Henderson RD, Wolter TD, Wijdicks EF. Anticipating mechanical ventilation in Guillain-Barré syndrome. Arch Neurol. 2001 Jun. 58 (6):893-8. [QxMD MEDLINE Link].
CDC. Botulism | Diagnosis and Treatment. CDC.gov. Available at https://www.cdc.gov/botulism/testing-treatment.html. June 1, 2021; Accessed: November 27, 2022.
Sandrock CE, Murin S. Clinical predictors of respiratory failure and long-term outcome in black tar heroin-associated wound botulism. Chest. 2001 Aug. 120 (2):562-6. [QxMD MEDLINE Link].
Merz B, Bigalke H, Stoll G, Naumann M. Botulism type B presenting as pure autonomic dysfunction. Clin Auton Res. 2003 Oct. 13 (5):337-8. [QxMD MEDLINE Link].
CDC. Botulism | Prevention. CDC.gov. Available at https://www.cdc.gov/botulism/prevention.html#anchor_1491857381171. June 8, 2022; Accessed: November 27, 2022.
CDC. Botulism | Home Canned Foods. CDC.gov. Available at https://www.cdc.gov/botulism/consumer.html. June 6, 2019; Accessed: November 27, 2022.
Klompas M, Branson R, Eichenwald EC, Greene LR, Howell MD, Lee G, et al. Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014 Aug. 35 (8):915-36. [QxMD MEDLINE Link].
Gould CV, Umscheid CA, Agarwal RK, Kuntz G, Pegues DA, Healthcare Infection Control Practices Advisory Committee. Guideline for prevention of catheter-associated urinary tract infections 2009. Infect Control Hosp Epidemiol. 2010 Apr. 31 (4):319-26. [QxMD MEDLINE Link].
Gaspar S, Peralta M, Marques A, Budri A, Gaspar de Matos M. Effectiveness on hospital-acquired pressure ulcers prevention: a systematic review. Int Wound J. 2019 Oct. 16 (5):1087-1102. [QxMD MEDLINE Link].
Bell T, O'Grady NP. Prevention of Central Line-Associated Bloodstream Infections. Infect Dis Clin North Am. 2017 Sep. 31 (3):551-559. [QxMD MEDLINE Link].
Ostrosky-Zeichner L, Sable C, Sobel J, Alexander BD, Donowitz G, Kan V, et al. Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting. Eur J Clin Microbiol Infect Dis. 2007 Apr. 26 (4):271-6. [QxMD MEDLINE Link].
Young PJ, Bagshaw SM, Forbes AB, Nichol AD, Wright SE, Bailey M, et al. Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial. JAMA. 2020 Feb 18. 323 (7):616-626. [QxMD MEDLINE Link].

Media Gallery

of 0

Author

William N Bennett, V, MD Staff Physician, Infectious Disease Service, Chair, Antimicrobial Stewardship, Department of Medicine, Wright-Patterson Medical Center; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences School of Medicine

William N Bennett, V, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Joseph M Yabes, Jr, MD, FACP Deputy Director, USAF HIV Medical Evaluation Unit, Associate Program Director, Infectious Disease Fellowhip, Brooke Army Medical Center; Core Faculty, Infectious Disease Fellowship, Chair, Virtual Health Subcommittee, San Antonio Uniformed Services Health Education Consortium (SAUSHEC); Assistant Professor, Department of Medicine, Uniformed Services University of the Health Sciences; Adjunct Assistant Professor, Department of Medicine, University of Texas Health Science Center at San Antonio

Joseph M Yabes, Jr, MD, FACP is a member of the following medical societies: American College of Physicians, Armed Forces Infectious Diseases Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Kirk M Chan-Tack, MD Medical Officer, Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration

Disclosure: Nothing to disclose.

David Hall Shepp, MD Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine

David Hall Shepp, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Received salary from Gilead Sciences for management position.

John Bartlett, MD † Professor Emeritus, Johns Hopkins University School of Medicine

John Bartlett, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Pharmacology, American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, American Thoracic Society, American Venereal Disease Association, Association of American Physicians, Infectious Diseases Society of America, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Acknowledgements

The views expressed herein are those of the author(s) and do not reflect the official policy or position of Wright Patterson Medical Center, Brooke Army Medical Center, the Defense Health Agency, Uniformed Services University of the Health Sciences, U.S. Army Medical Department, U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, the DoD, or the U.S. Government.