Botulism

INTRODUCTION — Botulism is a rare but potentially life threatening neuroparalytic syndrome resulting from the action of a neurotoxin elaborated by the bacterium Clostridium botulinum. This disease has a lengthy history; the first investigation of botulism occurred in the 1820s with a case series about hundreds of patients with "sausage poisoning" in a southern German town [1]. Several decades later in Belgium, the association was demonstrated between a neuromuscular paralysis and ham infected by a spore-forming bacillus that was isolated from the ham. The organism was initially named Bacillus botulinus after the Latin word for sausage, botulus.

The microbiology, pathogenesis, epidemiology, clinical manifestations, diagnosis, and treatment of botulism will be discussed here.

Infant botulism is discussed briefly here and in greater detail elsewhere. (See "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism'.)

MICROBIOLOGY AND PATHOGENESIS

●The causative organism – C. botulinum is a gram-positive, rod-shaped, spore-forming, obligate anaerobic bacterium. It is ubiquitous and easily isolated from the surfaces of vegetables, fruits, and seafood, and exists in soil and marine sediment worldwide [2]. C. botulinum is divided into four distinct phenotypic groups (I to IV); it is more commonly classified into seven serotypes (A to G) based on the antigenicity of toxin production. A single strain usually produces only one toxin, but some strains may produce multiple toxins [3]. Clostridium butyricum and Clostridium baratii are two other distinct Clostridia species that are known to have produced botulinum toxin (types E and F) [4].

C. botulinum spores are heat resistant and can survive 100°C at one atmosphere for five or more hours. However, spores can be destroyed by heating to 120°C for five minutes [5]. When appropriate environmental conditions are present, the spores will germinate and grow into toxin-producing bacilli. These environmental parameters include:

•Restricted oxygen exposure (either an anaerobic or semi-anaerobic environment).

•pH near 7.0 or greater. Growth is inhibited when the pH is <4.6; however, a low pH will not degrade existing toxin.

•A temperature of 25 to 37°C. Some strains may grow in temperatures as low as 4°C.

Contamination of food cannot reliably be suspected on the basis of appearance, odor, or taste. Some strains (A and B) produce proteolytic enzymes that denature and "spoil" food, producing an unpleasant appearance, taste, or smell. However, other strains do not have this effect.

●Botulinum toxin – Eight distinct C. botulinum toxin types have been described: A through H. Of these eight, types A, B, E, and rarely F, G, and H, cause human disease; C and D cause disease in animals such as cattle, ducks, and chickens. C. botulinum toxin type H was first reported in 2014 and was the first new botulinum toxin type to be recognized in over four decades [6,7]. In contrast with the spores, the toxin is a heat-labile polypeptide readily denatured by heating above 80°C. The polypeptide toxin is composed of a light and heavy chain with a combined molecular weight of 150 to 165 kDa.

Botulinum toxin is released as a single precursor polypeptide chain that is then cleaved by bacterial proteases into a fully active neurotoxin composed of a 50-kDa light chain and a 100-kDa heavy chain [8]. Although the precise molecular mechanism of botulinum neurotoxin action is not fully understood, evidence supports a multistep process that includes binding of the neurotoxin to specific receptors at the presynaptic nerve terminal, toxin internalization into the nerve cell with translocation across the endosomal membrane, and intracellular endopeptidase cleavage of proteins necessary for neurotransmitter release.

Botulinum toxin can affect both excitatory and inhibitory synapses but is more active in excitatory neurons. It inhibits the release of multiple compounds, including dopamine, serotonin, somatostatin, noradrenaline, and gamma aminobutyric acid. Because of its large size, the toxin is thought unlikely to be able to pass through the blood-brain barrier; however, evidence is mounting that it could reach the central nervous system through either systemic spread or axonal retrograde or anterograde transport.

Botulinum toxin is the most potent bacterial toxin and perhaps the most potent known poison. The minimum lethal dose in experimental mice of botulinum toxin is 0.0003 mcg/kg. By comparison, the MLDs for curare and sodium cyanide are 500 and 10,000 mcg/kg, respectively [9]. It is estimated that 1 gram of aerosolized botulism toxin could kill at least 1.5 million people [10].

The toxin itself has no smell or taste. If ingested, the toxin is primarily absorbed by the stomach and small intestine, although the large intestine can absorb the toxin as well. The toxin is resistant to degradation by gastric acidity and human alimentary enzymes. However, botulinum toxin is inactivated in chlorinated water after only 20 minutes of exposure and in fresh water after three to six days [11].

EPIDEMIOLOGY

Types of botulism and their sources — The modern syndrome of botulism occurs in several forms, differentiated by the mode of acquisition. The most common types are infant, foodborne, and wound botulism. Iatrogenic botulism and adult intestinal colonization are rarer types:

Infant botulism — Infant botulism occurs when C. botulinum spores are ingested, colonize the host's gastrointestinal (GI) tract, and release toxin produced in vivo. In the United States, most cases are thought to result from ingestion of environmental dust and soil containing C. botulinum spores. The incidence of reported cases is highest in California and Pennsylvania, states in which soil botulinum spore counts are high [12]. Infant botulism has classically been associated with the ingestion of raw honey. However, this is most likely a minor environmental reservoir, since widespread education of the public has done little to affect the incidence of infant botulism in the United States.

Infant botulism is discussed in more detail elsewhere. (See "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism'.)

Foodborne botulism — Foodborne botulism is caused by ingestion of food contaminated by preformed botulinum toxin. Toxin types A, B, and E have been associated with foodborne botulism.

Most cases of botulism are recognized when small outbreaks involving home-canned foods such as fruits, vegetables, and fish occur [13-16].

●In the United States, the highest rates of foodborne botulism have been reported among Alaska Natives as a result of ingestion of aged, fermented fish and marine mammals (eg, seal or whale blubber, dried herring) [17,18]. Surveillance data from the US Centers for Disease Control and Prevention (CDC) between 1947 and 2007 found a mean annual incidence of 6.9 cases per 100,000 Alaska Natives compared with an overall national rate of 0.0068 cases per 100,000 persons. Subsequently, confirmed cases of foodborne botulism have been reported annually from Alaska (whereas cases in other states are more sporadic) [19]. Toxin type E is the most commonly implicated type in foodborne botulism in Alaska [13].

Prison brew (also known as pruno, hooch, moonshine, or bootleg), an illicit beverage typically made by fermenting fruit and sugar in water along with bread or potato, has been identified as a major source of outbreaks within prison populations [20-22].

●In China, home-fermented tofu and other fermented bean products cause more than half of the cases of foodborne botulism [23].

Commercial products and restaurants are occasionally sources; specific commercial sources have included carrot juice and sausage that were improperly refrigerated [14,24-30]. Foods that have been recalled for potential C. botulinum contamination can be searched in catalogs maintained by food regulatory agencies in the United States, Canada, and the European Union.

In a systematic review of cases of foodborne botulism between 1920 and 2014, 197 reported outbreaks were identified, 55 percent of which occurred in the United States [31]. Outbreak sizes ranged from 2 to 97 (median 3) affected individuals. Commercial sources were associated with an outbreak size ≥12 cases. Toxin type A has caused the majority of the outbreaks in the United States, Europe, and Asia, whereas type E has caused the majority in Canada [31].

Wound botulism — C. botulinum can infect wounds and subsequently produce neurotoxin in vivo. In theory, wound botulism should only be associated with puncture wounds, subcutaneous abscesses, and deep space infections, which provide the anaerobic environment required for spores to germinate and the organism to thrive. Accordingly, wound botulism is associated with injection drug use, particularly with "black tar" heroin and subcutaneous or intramuscular injection (including “skin popping”) [32,33]. Recurrent wound botulism has occurred in some people who inject drugs [34].

However, cases have also been described involving abrasions, lacerations, open fractures, surgical incisions, and even a closed hematoma without appreciable skin defect [35]. A case has been reported of pelvic abscess, paralysis, and toxemia due to C. botulinum following a laparoscopic appendectomy [36].

Wound botulism has also been reported in patients who inhale cocaine [37]. In that case series, patients presented with sinusitis; C. botulinum was isolated from a sinus aspirate in one patient.

Rarer types

●Iatrogenic botulism – Iatrogenic cases of botulism have been rarely reported in patients who have received botulinum toxin for cosmetic or medical indications [38-41].

As an example, four cases of botulism were described in patients who had received botulinum toxin injections using an unlicensed, highly concentrated preparation of botulinum toxin A [38]. The patients may have received doses as high as 2857 times the estimated human lethal dose by injection and had serum toxin levels 21 to 43 times the estimated lethal human dose by injection. After administration of equine serum antitoxin, all patients survived but required prolonged mechanical ventilation and physical rehabilitation. Milder cases of shorter duration have been described in patients who received lower, standard doses of cosmetic botulinum toxin [40].

The safety record of botulism toxin for cosmetic use is discussed in detail separately. (See "Overview of botulinum toxin for cosmetic indications", section on 'Clinical safety record'.)

●Adult intestinal colonization – Adult intestinal colonization is also known as adult intestinal toxemia or enteric infectious botulism. Similar to infant botulism, it occurs when food contaminated with C. botulinum spores (but not preformed toxin) is ingested, and the bacteria colonizes the GI tract and produces toxin in vivo. (See 'Infant botulism' above.)

This a rare form of botulism. Between 1980 and 2018, only 33 cases were reported in the literature [42]. After infancy, the GI tract is typically resistant to colonization by C. botulinum. The alterations in intestinal flora or gut mucosa that predispose adults to intestinal colonization are unknown. Botulism attributed to intestinal colonization has been reported in patients with inflammatory bowel disease, recent GI surgery, and achlorhydria, as well as in an allogeneic hematopoietic cell transplant recipient [42,43].

Incidence — Botulism occurs globally. In the United States, approximately 200 cases of botulism are reported to the CDC each year [19]. Approximately 70 to 75 percent of cases are infant botulism, 20 to 25 percent are foodborne, and 5 to 10 percent are wound-related. Botulism due to adult intestinal colonization botulism is extremely rare.

In the United States, the incidence of infant and foodborne botulism has remained stable over the past several decades. In contrast, the incidence of wound botulism has increased over time [44]. The ongoing opioid epidemic has the potential to fuel further increases in wound botulism incidence.

Potential for bioterrorism — Because C. botulinum toxin is extremely potent, it has been identified as a potential agent of bioterrorism [45,46]. The 1972 Biological and Toxin Weapons Convention prohibited both research on and production of bioweapons [45], although it has been suspected that Iran, Iraq, North Korea, and Syria have botulinum toxin supplies [47]. Despite the potency of C. botulinum toxin, technical complexities in concentrating and stabilizing the toxin for aerosolization have remained major barriers to its deployment as a bioterrorism agent [45,46]. Aerosolized botulinum toxin was deployed unsuccessfully in Tokyo by the religious sect Aum Shinrikyo in 1995 prior to their use of sarin [48].

Aerosolized botulinum toxin, if successfully deployed, would likely produce an acute symmetric descending flaccid paralysis with prominent bulbar palsies (diplopia, dysarthria, dysphonia, and dysphagia) within 12 to 72 hours of exposure [45,49].

Contamination of a common food or water source resulting in mass foodborne botulism is another possible mode of attack [49].

CLINICAL MANIFESTATIONS

Characteristic features — The classic presentation of botulism is acute onset of bilateral cranial neuropathies associated with symmetric descending weakness [5,50]. Other key features of the botulism syndrome include:

●Absence of fever

●Symmetric neurologic deficits

●Normal sensorium and mental status

●Normal or slow heart rate and normal blood pressure

●Absence of sensory deficits, with the exception of blurred vision

In a report of 322 laboratory- or epidemiologically-confirmed cases of botulism in the United States from 2002 to 2015, 99 percent were afebrile, 98 percent had at least one symptom related to cranial nerve dysfunction, 93 percent had descending paralysis, and 91 percent remained alert and oriented [51]. Neurologic deficits were primarily bilateral; unilateral facial paralysis, extraocular palsy, and ptosis each occurred in fewer than 15 percent of cases.

Additional details of the major clinical features include:

●Cranial nerve dysfunction – The onset of symptomatic illness is characterized by cranial nerve dysfunction, which includes blurred vision (secondary to fixed pupillary dilation and palsies of cranial nerves III, IV, and VI), diplopia, nystagmus, ptosis, dysphagia, dysarthria, and facial weakness. In a systematic review of 400 adults with botulism, 93 percent had cranial nerve findings at the time of presentation [52]. One-third of these patients had one to two cranial nerves affected, one-third had three or four cranial nerves affected, and the remaining one-third had five or more cranial nerves affected.

The most commonly reported cranial nerve-related findings among non-infant children with botulism are dysphagia, and dysarthria [53].

●Muscle weakness/paralysis – Descending muscle weakness usually progresses from the trunk and upper extremities to the lower extremities, and proximal muscles are typically involved before distal muscles [50]. Urinary retention and constipation resulting from smooth muscle paralysis are common. As above, the weakness is typically bilateral, although asymmetric limb weakness has been reported. Sensory defects or paresthesias are uncommon [54].

●Respiratory symptoms – Respiratory difficulties (eg, dyspnea) with or without obvious extremity weakness are common, often requiring intubation and mechanical ventilation. Diaphragmatic paralysis related to descending muscle weakness is the main cause of dyspnea. Respiratory symptoms related to upper airway compromise from cranial nerve dysfunction may also occur. In a systematic review of 400 adults with botulism, approximately 40 percent presented with respiratory involvement (shortness of breath, dyspnea, respiratory distress or failure) at the time of hospitalization; however, only 42 percent of these patients had concurrent evidence of extremity weakness [52]. Although respiratory failure without a history of prior neurologic symptoms (including cranial neuropathies) has been reported, this is a highly unlikely presentation that more likely reflects incomplete history or evaluation [50].

Type-specific clinical features — In addition to the classic neurologic features of botulism (see 'Characteristic features' above), certain clinical features occur more commonly with specific types of botulism:

●Infant botulism – The clinical features of infant botulism are discussed in detail elsewhere. (See "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism'.)

●Foodborne botulism – The onset and evolution of symptoms in foodborne botulism are highly variable. Symptoms usually begin within 12 to 36 hours after ingestion of the preformed toxin, but the incubation period may range from several hours to two weeks [52,53].

Nonspecific gastrointestinal (GI) symptoms, including nausea, vomiting, abdominal pain, and diarrhea are common in patients with foodborne botulism [55-57]. These can occur as prodromal symptoms, prior to the development of cranial neuropathies and descending weakness, but can also occur at any time throughout the course of the illness [58]. They can rarely be the predominant presenting complaint [56].

Some presentations of foodborne botulism can be quite mild, with neurologic involvement that is minimal or confined to the ocular cranial nerves. As an example, in a small outbreak associated with home-salted fish contaminated with botulinum toxin type E, all five patients presented with GI symptoms, and only two had cranial nerve palsies, which were minimally symptomatic [56].

●Wound botulism – Wound botulism is similar to foodborne botulism in its presentation and clinical course, with three exceptions. The prodromal GI symptoms that are common in patients with foodborne botulism are typically absent with wound botulism; the incubation period of wound botulism is longer (approximately 10 days); and fever and leukocytosis, which are absent in foodborne botulism, occur in approximately half of patients with wound botulism [35]. Fever and leukocytosis probably result from concurrent bacterial infection of the wound by non-clostridial species.

Clinical course — The clinical features of botulism evolve over a few hours to a few days and may last for months [50].

Typically, minor visual complaints (or with foodborne botulism, GI complaints) are subsequently followed by more pronounced cranial nerve symptoms, which in turn are followed by bilateral descending weakness (see 'Characteristic features' above). In some cases, the extent of the weakness is limited to the cranial nerves, whereas in other cases, it may progress to complete bilateral flaccid paralysis [52].

Progression to respiratory distress and failure can occur rapidly; in a systematic review of 400 patients with botulism, approximately 60 percent of the individuals who were admitted with respiratory symptoms reported <48 hour interval between illness onset and hospitalization [52]. Among those who required intubation, 87 percent were intubated within the first two days of hospitalization.

Recovery from botulism occurs with development of new nerve terminals [50]. Thus, botulism can result in prolonged paralysis and require hospitalization for weeks to months. (See 'Prognosis' below.)

Laboratory and imaging findings — In the absence of a complicating or concurrent condition, routine laboratory and imaging findings in patients with botulism are typically normal.

●Complete cell counts are usually normal, although white blood cell count can be elevated in patients with secondary infectious complications, such as those with wound botulism. (See 'Type-specific clinical features' above.)

●Cerebrospinal fluid (CSF) analysis is usually normal [51]. Elevated CSF protein has occasionally been reported (in 13 percent in one series) [51].

●Botulism does not cause neuroimaging abnormalities.

Electrodiagnostic study findings — Abnormal electromyographic (EMG) and nerve conduction findings in patients with botulism include reduction in compound muscle action potential and M-wave amplitudes, excessive action potentials, and frequency-varying response to repetitive nerve stimulation. However, early in the course of disease, these studies can be normal.

Abnormal electrodiagnostic study findings associated with botulism are discussed in detail elsewhere. (See "Neuromuscular junction disorders in newborns and infants", section on 'Diagnosis' and "Overview of neuromuscular junction toxins", section on 'Neurophysiology'.)

DIFFERENTIAL DIAGNOSIS — Botulism is commonly mistaken for other conditions on initial presentation, highlighting the importance of considering the diagnosis in patients with cranial nerve palsies with or without muscle weakness. (See 'When to consider the possibility of botulism' below.)

In a study of 167 cases of botulism for which treating clinicians indicated their differential diagnoses at the time of public health consultation, the most common alternative diagnoses were Guillain-Barré syndrome, myasthenia gravis, stroke, poisoning or intoxication, Lambert-Eaton myasthenic syndrome, and tick paralysis [52].

●Other neuromuscular junction disorders – Myasthenia gravis can be confused with botulism because it also commonly presents with ocular findings (ptosis and/or diplopia) and sometimes with dysphagia and dysarthria. Pupillary paralysis and dilation, which can be seen with botulism, does not occur with myasthenia gravis. Lambert-Eaton myasthenic syndrome, another neuromuscular junction disorder, also presents with weakness but less commonly with ocular muscle involvement. These conditions can usually be distinguished from botulism by electromyography (EMG) and are discussed in detail elsewhere. (See "Overview of neuromuscular junction toxins" and "Differential diagnosis of myasthenia gravis".)

●Guillain-Barré syndrome (GBS) – Although GBS is also characterized by a progressive and symmetric muscle weakness, unlike botulism it usually involves ascending paralysis, sensory findings, and elevated cerebrospinal fluid (CSF) protein [35]. These are discussed in detail elsewhere. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Differential diagnosis'.)

●Other causes of acute bilateral weakness – These include stroke (in particular brainstem stroke), heavy metal intoxication, and poliomyelitis. Clinical and imaging features may help distinguish these from botulism. As examples, neuroimaging is abnormal in stroke, and poliomyelitis is typically asymmetric. (See "Overview of the evaluation of stroke", section on 'Confirming the diagnosis' and "Poliomyelitis and post-polio syndrome", section on 'Diagnosis'.)

Less likely diagnoses include tetrodotoxin and shellfish poisoning, tick paralysis, West Nile virus, and antimicrobial-associated paralysis (eg, with aminoglycosides) [55]. (See "Overview of neuromuscular junction toxins", section on 'Drugs' and "Overview of shellfish, pufferfish, and other marine toxin poisoning" and "Tick paralysis" and "Clinical manifestations and diagnosis of West Nile virus infection".)

The differential diagnosis and evaluation of acute weakness in adults are discussed elsewhere. (See "Evaluation of the adult with acute weakness in the emergency department", section on 'Life-threatening and other serious causes of bilateral weakness'.)

The differential diagnosis and evaluation of infants with acute weakness are also discussed separately. (See "Etiology and evaluation of the child with weakness".)

DIAGNOSIS

When to consider the possibility of botulism — Having a low threshold to suspect botulism is essential for the timely diagnosis. The possibility of botulism should be considered in any patient with acute onset of unexplained cranial nerve abnormalities. It should also be considered in patients with suspected myasthenia gravis or Guillain-Barre syndrome (GBS). In infants, botulism should be considered when there is acute onset of weak suck, ptosis, inactivity, and constipation (eg, floppy baby syndrome).

Specifically, the Centers for Disease Control and Prevention (CDC) in the United States suggests that botulism be suspected in patients who meet the following three criteria (table 1):

●At least one specific symptom of cranial neuropathy – These include blurred or double vision, difficulty speaking, voice change, dysphagia or drooling, thick tongue sensation.

●At least one specific sign of cranial neuropathy – These include ptosis, extraocular palsy or fatigability, decreased tracking, facial paresis or loss of expression, poor feeding or suck, fixed pupils, descending paralysis beginning with cranial nerves.

●Lack of fever.

These three criteria are met in the majority of reported cases of botulism. In a study that included 241 cases of botulism recorded in the National Botulism Surveillance Database in the United States, those three clinical criteria were met in 89 percent of patients [59]. In a medical record review of 99 other botulism cases from the database, these clinical criteria would have been able to identify 78 percent within 48 hours of hospitalization. Thus, these criteria could be helpful for clinicians to prompt consideration of botulism earlier in the course of disease. However, the specificity of these three criteria is unknown, and the absence of one of these criteria does not rule out the possibility of botulism. As an example, fever may be present because of a reason other than botulism, as with concurrent bacterial infection in wound botulism. (See 'Wound botulism' above.)

Initial evaluation and presumptive clinical diagnosis — Once botulism is suspected (see 'When to consider the possibility of botulism' above), careful history and physical examination are paramount to evaluate for other features consistent with botulism, assess for potential exposure, and rule out other causes. If the clinical presentation is sufficiently consistent with botulism to make a presumptive clinical diagnosis (cranial neuropathy with symmetric descending paralysis, particularly if the patient is alert, afebrile, and has no sensory deficit), public health officials should be contacted for assistance in diagnostic testing and treatment, which should be initiated before results of confirmatory diagnostic tests return. (See 'Contact public health officials' below and 'Confirming the diagnosis' below and 'Treatment' below.)

●Evaluation – History and physical examination should focus on signs and symptoms of cranial neuropathy, evidence of symmetric axial and extremity weakness, and respiratory status (see 'Characteristic features' above). Patients with botulism are typically fully alert but may have ptosis, dysarthria, and gait disturbances that could mimic intoxication or altered sensorium, and examination should distinguish these. Neurologic examination should also evaluate for other deficits (eg, sensory defects or unilateral findings) that would be atypical for botulism, although these do not rule out the possibility of botulism. In contrast to polyneuropathies that could mimic botulism (eg, GBS), reflexes are typically normal in patients with botulism unless the affected muscle group is completely paralyzed [60].

Physical examination should also include a thorough skin and scalp examination for ticks, as patients with tick paralysis can present similarly. (See "Tick paralysis", section on 'Diagnosis'.)

In addition to elucidating signs and symptoms consistent with botulism, it is important to include a thorough history to identify possible exposures, such as ingestion of home canned foods, exposure to other possible food sources (including honey in infants <12 months of age), injection drug use, trauma, and cosmetic use of botulinum toxin. The possibility of bioterrorism should also be considered when clusters of patients present with suspected botulism.

Other general laboratory or imaging studies are not necessary for the diagnosis of botulism but may be warranted to rule out other causes (eg, neuroimaging may be appropriate to evaluate for brainstem disease). Patients with botulism are typically afebrile without meningismus or headache, so lumbar puncture is not indicated. (See "Neuroimaging of acute stroke", section on 'Approach to imaging'.)

Electrodiagnostic studies (including repetitive nerve stimulation, electromyography, and nerve conduction studies) are also not necessary for making the diagnosis but can be helpful in raising or lowering suspicion for botulism, as certain findings are suggestive of botulism and can distinguish it from other neuromuscular disorders. (See "Neuromuscular junction disorders in newborns and infants", section on 'Diagnosis' and "Overview of neuromuscular junction toxins", section on 'Neurophysiology'.)

Tensilon (edrophonium) tests to rule out myasthenia gravis, if available, should not be conducted, as they are often falsely positive in patients with botulism [61].

●Making a presumptive clinical diagnosis – A presumptive diagnosis can be made on clinical findings alone, when signs and symptoms are consistent with botulism (see 'Characteristic features' above). Specifically, among causes of flaccid paralysis, botulism is distinctive because of the early involvement of cranial nerves, the symmetric descending paralysis, and the lack of sensory neuropathy, and these features are sufficient to make a presumptive diagnosis. Although exposure to a potential source of botulism should also increase clinical suspicion (see 'Types of botulism and their sources' above), lack of clear exposure does not rule out the possibility.

In settings where health care facilities are at surge capacity (eg, outbreak settings), meeting the three general criteria discussed above (table 1) may be sufficient to make the presumptive diagnosis [50], although typically a more detailed assessment of neurologic findings to ensure they are consistent with botulism is warranted.

Similar symptoms in individuals who have similar exposures (eg, have eaten the same foods) should lower the threshold for making a presumptive diagnosis of botulism.

If botulism is suspected, but the level of suspicion is not quite high enough to make a presumptive diagnosis, close serial neurologic monitoring is warranted to assess for progression of weakness.

Contact public health officials — In the United States, clinicians caring for patients with suspected botulism should contact the state health department immediately for assistance with the clinical and laboratory evaluation. After hours, regional poison centers (1-800-222-1222) can help contact on-call state health department representatives.

●For non-infant botulism cases, state public health officials can reach the CDC clinical emergency botulism service at 770-488-7100.

●For suspected infant botulism occurring in any state, the California Department of Health Services, Infant Botulism Treatment and Prevention Program should be contacted (www.infantbotulism.org or 510-231-7600).

Every case of foodborne botulinum requires investigation by public health authorities under the guidance of the CDC. Suspected food sources should be retained for later investigation and testing when appropriate.

Confirming the diagnosis — Botulism is confirmed through toxin detection or C. botulinum growth in relevant specimens. However, these confirmatory tests do not yield timely results, so the decision to administer antitoxin should be based on the presumptive clinical diagnosis of botulism (see 'Initial evaluation and presumptive clinical diagnosis' above) and not be delayed while awaiting results of confirmatory diagnostic studies. (See 'Antitoxin therapies' below.)

Specimen collection — Specimens should be collected for diagnostic testing as soon as possible because toxin levels decrease over time; additionally, serum and any gastric aspirate specimens should be collected for testing prior to antitoxin administration [50]. Public health experts should be consulted for guidance on specimen collection.

For suspected foodborne or infant botulism, serum, stool, gastric fluid, and the suspected food source should be submitted for testing. For suspected wound botulism, serum and wound specimens should be submitted [50]:

●Serum – The optimal amount is at least 10 to 15 mL (smaller volumes to a minimum of 4 mL can be used for children). Send for toxin testing.

●Stool – The optimal amount is 10 to 20 g stool, although smaller amounts can be adequate, and rectal swabs are acceptable in infants and young children. Send for toxin testing and anaerobic culture.

●Gastric fluid/aspirate – The optimal amount is 5 to 10 mL. Send for toxin testing and anaerobic culture.

●Suspected food source – The optimal amount is 10 to 20 g. The entire food item should be submitted in original containers, if possible. Empty containers with residual food can also be tested. Send for toxin testing and anaerobic culture.

●Wound specimens – Pus or tissue specimens yield the best results. A wound swab can be sent, although its sensitivity for detecting C. botulinum is lower. Send for anaerobic culture.

All specimens should be immediately refrigerated after collection and kept at this temperature during transport. They should not be frozen.

When collecting specimens for anaerobic culture, clinicians should generally consult with their microbiology laboratory to ensure that they are using proper technique and collecting the specimens in appropriate anaerobic transport media.

Diagnostic testing and interpretation — In a symptomatic individual, the diagnosis of botulism is confirmed by identification of toxin in serum, stool, vomitus, or consumed food sources or by isolation of C. botulinum (or other botulinum toxin-producing Clostridium species) from stool, wound specimens, or consumed food sources. Laboratory confirmation is not necessary in an individual with suggestive clinical findings who shared the same food with a laboratory-confirmed case. Asymptomatic individuals who may have been exposed do not warrant diagnostic testing.

Laboratory testing for botulism is performed by special laboratories. In the United States, the locations of these laboratories can be obtained by contacting state health department. State public health officials can reach the CDC clinical emergency botulism service at 770-488-7100.

●Toxin detection – Preliminary results of toxin testing generally take 24 to 48 hours and final results take 96 hours [50].

Toxin is traditionally detected using a mouse bioassay, in which mice are followed for symptoms of botulism after injection with the specimen with or without concurrent administration of antitoxin [60,62]. Other techniques for toxin identification include enzyme-linked immunosorbent assays (ELISAs) and mass spectroscopy, both of which can identify the toxin protein, and polymerase chain reaction (PCR), which identifies bacterial genetic material.

●C. botulinum detection – Anaerobic culture to grow and identify the organism can take up to two to three weeks. Most clinical laboratories do not perform the specific tests needed to distinguish toxigenic from nontoxigenic Clostridium species.

Negative botulinum toxin tests or culture do not necessarily rule out the possibility of botulism in symptomatic individuals. This is another reason that treatment should not be delayed for diagnostic confirmation.

●Botulinum toxin can be detected in the serum up to 12 days following ingestion [25,63], so if specimens are tested later in illness, the toxin level may be below the limit of detection. In such cases, electrodiagnostic testing results can help support the diagnosis of botulism, as these can remain abnormal for weeks. (See "Overview of neuromuscular junction toxins", section on 'Neurophysiology'.)

●In patient with wound botulism, serum assays for toxin are frequently negative. As an example, among a cohort of 73 individuals with injection drug use-associated wound botulism, only 50 (68 percent) had toxin detected from the serum [64]. Additionally, anaerobic culture of wound specimens may not be positive, particularly if antibiotics had already been administered [50].

●In the event of an attack with aerosolized botulinum toxin, the level of toxin in serum or other specimens may not be high enough to be detected [60]. Thus, negative toxin tests should not rule out the possibility if large numbers of patients present with features clinically consistent with botulism.

TREATMENT — The treatment approach to all patients with botulism includes prompt intubation for respiratory failure, administration of antitoxin, and intensive care for those with paralysis.

A detailed discussion of infant botulism is presented separately. (See "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism'.)

Supportive/respiratory care and monitoring

●Site of care – Any patient with clinical signs, symptoms, or history suspicious for botulism should be hospitalized immediately and meticulously monitored for signs of progressive weakness and respiratory failure. Hospitalization for patients with botulism is often prolonged. (See 'Clinical course' above.)

●Respiratory care – Respiratory failure is the primary cause of death in patients with botulism. Monitoring should include serial assessment of oxygenation, ventilation, and upper airway integrity. This includes clinical evaluation of work of breathing (eg, respiratory rate, accessory muscle use) and objective measures (eg, spirometry, pulse oximetry, and arterial blood gas measurement) [52]. Clinicians should be aware that facial paralysis may obscure clinical distress and that patients with impending respiratory failure may not have hypoxia until the late stages.

Intubation should be considered for those patients with inadequate or worsening upper airway competency and those with a vital capacity less than 30 percent of predicted. It is reasonable to use intubation thresholds similar to those for Guillain Barré syndrome. (See "Guillain-Barré syndrome in adults: Treatment and prognosis", section on 'Ventilatory status' and "Guillain-Barré syndrome in children: Treatment and prognosis", section on 'Monitoring and supportive care'.)

Infants and severe adult cases may require prolonged mechanical ventilation. In one systematic review of 402 patients with foodborne or wound botulism, the reported intubation rate was 46 percent [52].

●Other supportive care – Patient’s ability to swallow should be assessed. Supportive care should also include small volume continuous nasogastric feedings to minimize aspiration risk [65]. When severe ileus is present, parenteral hyperalimentation may be required.

Antitoxin therapies

Timing and rationale — Antitoxin is the main therapeutic option for botulism and should be administered as soon as the presumptive clinical diagnosis of botulism is made. Specifically, if the clinical suspicion for botulism is high (eg, the patient is alert and afebrile but has the acute onset of bilateral cranial neuropathies associated with symmetric descending weakness) and symptoms are progressing, antitoxin should be administered as soon as possible. It should not be delayed while awaiting results of diagnostic studies. In the United States, clinicians caring for patients with suspected botulism should contact the state health department immediately for assistance with the decision to administer botulinum antitoxin (BAT) and to obtain a supply of antitoxin.

BAT binds to circulating neurotoxins and prevents their binding to the neuromuscular junction, potentially preventing progression to respiratory failure if administered soon enough. Because BAT cannot reverse paralysis, prompt administration early in the course of disease is critical. Nevertheless, individuals with suspected botulism and progressive symptoms should be treated with BAT regardless of time since onset of illness. BAT is likely less beneficial to those who have already progressed to complete paralysis, particularly if symptoms had been ongoing for more than seven days prior. Dosing and administration depend on the formulation of botulinum toxin available. (See 'Administration' below.)

Data informing the efficacy of BAT are limited and uncontrolled but demonstrate a benefit. In a meta-analysis of 61 studies and case series of patients with botulism, antitoxin was associated with a reduction in mortality (odds ratio [OR] 0.22, 95% CI 0.17-0.29), although there was substantial heterogeneity across studies [66]. Among the 27 studies that reported on toxin type involved and antitoxin type used, the results still demonstrated a mortality benefit (OR 0.16, 95% CI 0.09-0.30) without heterogeneity.

Some studies also suggest that earlier administration (eg, within the first 48 to 96 hours of presentation) of BAT is associated with reduced mortality compared with later administration [66,67].

Administration — Various forms of botulism therapies are available worldwide. In the United States, there are two botulism therapies available.

●Equine serum heptavalent BAT is used to treat non-infant botulism

●Human-derived botulism immune globulin is used for infant botulism

A pentavalent antitoxin formulation is available within the Department of Defense but is not available for public use.

In other regions of the world, clinicians should contact their local health department for information on available BATs.

Botulinum antitoxin (BAT) for non-infant botulism — Equine serum heptavalent BAT contains antibodies to seven of the eight known botulism toxin types (A through G).

●How to obtain – In the United States, BAT is available through state health departments, which can obtain antitoxin through the Centers for Disease Control and Prevention (CDC) [68]. Regional poison centers across the United States may also be of assistance in contacting on-call state health department representatives after hours (calling 1-800-222-1222 automatically forwards the caller to the regional poison center). If there is no response, the CDC’s clinical emergency botulism service should be contacted (770-488-7100) [55].

●Dose – The dose depends on age [69]:

•Adults: One vial should be administered intravenously (IV) [50,69]. There is no clear evidence that additional doses are beneficial. If an adult has progressive weakness more than 24 hours following antitoxin administration, the possibility of alternate causes should be considered. However, if the suspicion for botulism and ingestion of a high amount of toxin remains, an additional dose of antitoxin may be reasonable, under the guidance of public health officials.

•Children aged 1 to 17 years: 20 to 100 percent of the adult dose, depending on weight, is recommended [69]. However, the amount of toxin that requires neutralization is dependent on the amount ingested and is not proportional to weight. Thus, children with progressive weakness despite weight-based antitoxin receipt may have ingested a large amount of toxin and may benefit from more antitoxin.

•Infants <1 year of age: Infants who are thought to have foodborne botulism (ie, have ingested the preformed toxin) should be treated with the equine serum heptavalent BAT; 10 percent of the adult dose might be appropriate, depending on public health consultation [69].

●Risk of hypersensitivity reaction – Equine serum heptavalent BAT used for noninfant botulism can cause sensitization and anaphylaxis, with an estimated rate of anaphylaxis of 1 to 2 percent [70]. Given the relatively low rate of anaphylaxis, skin testing prior to administration is not recommended [50]. However, BAT should be administered in a setting where anaphylaxis can be managed (eg, where epinephrine and antihistamines are available), and for individuals at risk of an acute hypersensitivity reaction (eg, those with allergies to horses, asthma, or seasonal allergies), BAT should be initiated at the lowest rate achievable [69].

As with other antitoxin formulations, human data informing efficacy are limited. In a study of 104 patients with confirmed botulism who were treated with BAT, the overall mortality rate was 7 percent [67]. Treatment within two days of symptom onset was associated with shorter hospital and intensive care unit stays and a non-statistically significant trend toward lower mortality. Other data on the potential mortality benefit with BAT in general are discussed elsewhere. (See 'Timing and rationale' above.)

Although BAT does not contain antibodies to the H toxin, there is some evidence that it may be beneficial in botulism associated with H toxin. One study has suggested that the H toxin has a hybrid-like structure with regions of similarity to the A and F toxins [71]. In addition, the toxic effects of the H toxin were completely eliminated by existing serotype A antitoxins, including those contained in BAT.

Most side effects associated with BAT are nonserious. In a study of 249 patients who had received BAT, 9 percent had at least one adverse effect [67]. These included fever, chills, rash, itching, agitation, and nausea. Only one patient, a child, had a serious adverse event: hemodynamic instability. Because antitoxin used for noninfant botulism is derived from horse serum, anaphylaxis and serum sickness may occur. Other reviews have reported incidences of 20 percent for serum sickness and 3 percent for anaphylaxis [70,72].

BAT was approved by the US Food and Drug Administration (FDA) in 2013 [73] and replaces earlier formulations. It is maintained in the Strategic National Stockpile and distributed through the CDC's drug service.

Botulinum immune globulin for infant botulism — Infants less than one year of age with botulism usually have infant botulism (ie, ingestion of C. botulinum spores followed by toxin production in vivo).

●Infant botulism is treated with human-derived intravenous botulism immune globulin (called BIG-IV or BabyBIG). BIG-IV should be administered as early as possible in the illness.

Clinicians in the United States should contact the California Department of Health Services' Infant Botulism Treatment and Prevention Program whenever infant botulism is suspected (www.infantbotulism.org or 510-231-7600).

Treatment of infant botulism is discussed in detail elsewhere. (See "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism'.)

●Infants may also have foodborne botulism (ie, ingestion of pre-formed toxin), which should be suspected if the affected infant is a part of a group or outbreak of botulism cases or has ingested food known to contain botulinum toxin. In such cases, treatment is with equine heptavalent BAT. (See 'Botulinum antitoxin (BAT) for non-infant botulism' above.)

Other management issues

Wound management

●Debridement – Patients presenting with wound botulism should undergo wound debridement to reduce bacterial burden and remove tissue contaminated with toxin, even if it appears unimpressive. These patients should receive tetanus boosters as well if it has been five or more years since their last immunization.

●Antibiotic therapy – We do not routinely administer antibiotics to target C. botulinum in patients with wound botulism when there is no evidence of wound infection (eg, no leukocytosis, fever, an abscess, or cellulitis). There is no evidence that antibiotic therapy has any benefit in the treatment of botulism; for other types of botulism, it is specifically not recommended because of the theoretical risk of additional toxin release with organism lysis [50]. However, antibiotics (eg, penicillin 3 million units IV every four hours in adults) have been used for wound botulism to try to decrease organism burden in case series and reports without clear adverse effects [74-76], so it is reasonable for clinicians to choose to administer antibiotics following antitoxin administration.

If patients do have features suggestive of wound infection, antibiotic therapy is appropriate. In such cases, broader-spectrum antimicrobial therapy is warranted because of the risk of a polymicrobial infection. Appropriate regimens depend on the extent of infection (eg, abscess, cellulitis, or necrotizing infection). Contemporary susceptibility testing studies suggest that in addition to penicillins and metronidazole, C. botulinum is also likely susceptible to third-generation cephalosporins (eg, ceftriaxone), vancomycin, and trimethoprim-sulfamethoxazole, which are often used in such infections [77]. However, we avoid certain agents because of potential toxicity in the setting of botulism. Specifically, we avoid tetracyclines and clindamycin if possible; although not frequently used for skin and soft tissue infections, aminoglycosides and polymyxins should also be avoided. The reasons are discussed elsewhere. (See 'No or limited role for other interventions' below.)

Specific regimens (including duration of antimicrobial treatment) for skin and soft tissue infections are discussed elsewhere. (See "Skin abscesses in adults: Treatment", section on 'Antimicrobial selection' and "Acute cellulitis and erysipelas in adults: Treatment", section on 'Selecting an antibiotic regimen' and "Necrotizing soft tissue infections", section on 'Antibiotic therapy'.)

No or limited role for other interventions

Bowel purgative agents — For foodborne botulism, laxatives, enemas, or other cathartics can be given, provided no significant ileus is present. However, there is no evidence that any of these have an effect on botulism.

Antibiotics — Antibiotics are specifically not recommended for types of botulism other than wound botulism [50]. In those with infant botulism or adults with suspected gastrointestinal botulism, there is a theoretical concern that lysis of intraluminal C. botulinum with antibiotic therapy could release additional toxin that could be absorbed [60,78]. (See "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism'.)

If antibiotics are necessary for other comorbid conditions (eg, pneumonia), certain antibiotics should be avoided, if possible, because of the possibility of neuromuscular blockade and thus potentiation of the effects of botulinum toxin [79]. In particular, the aminoglycosides can block neuromuscular transmission and have been associated with exacerbated weakness in animal studies and small case series of infant botulism [79,80]. The potential for neuromuscular blockade is highest with neomycin, followed by gentamicin, streptomycin, kanamycin, amikacin, then tobramycin. Tetracyclines (through calcium chelation), clindamycin (through inhibition of acetylcholine release) and polymyxins also potentiate neuromuscular blockade and should be avoided if possible.

PREVENTION

Avoiding exposure — Since most cases of botulism are transmitted through food, the most critical aspect of botulism prevention is proper food handling and preparation [78,81]. Good home-canning techniques (eg, following pressure canner/cooker instructions regarding minimum cooking time, pressure, and temperature) will destroy spores. Food from damaged cans (cans with slits, holes, dents, or bulges) should not be consumed. Both home-canned items (especially foods with low acid content such as corn, green beans, asparagus, and beets) and commercial products (especially those associated with improper handling during manufacturing; examples including carrot juice, tomatoes, chopped garlic in oil, canned cheese sauce, baked potatoes wrapped in foil, and chili peppers) have been sources of botulism. Botulinum toxin is highly heat labile; therefore, boiling home-canned foods for at least 10 minutes before consumption will render the food safe.

Known preventive strategies for infant botulism are limited to avoidance of honey in infants less than 12 months of age; older children can safely ingest honey.

The most important measure for the prevention of wound botulism is prompt medical evaluation and treatment of infected wounds.

Possible sources are discussed in greater detail above. (See 'Types of botulism and their sources' above.)

No vaccine available — An investigational pentavalent botulinum toxoid vaccine was available from 1965 until 2011 from the United States Centers for Disease Control and Prevention (CDC) for use in individuals at risk for occupational exposure to botulinum serotypes A, B, C, D, and E [82]. The CDC discontinued the availability of this vaccine in 2011 due to a decline in the immunogenicity of the vaccine (which was manufactured more than 30 years earlier) and an increase in local reactions to the vaccine following booster doses.

PROGNOSIS

●Duration of paralysis and hospitalization – For patients who progress to respiratory failure and mechanical ventilation, paralysis can be prolonged and require hospitalization for weeks to months; however, those with less severe illness may have faster recovery [83-86]. As an example, in one study of 21 individuals with wound botulism, the median length of stay was 32 days for individuals who were on mechanical ventilation compared with 7 days for others [83]. As discussed elsewhere, prompt administration of antitoxin has also been associated with shorter duration of hospitalization [84,86]. (See 'Antitoxin therapies' above.)

●Neurologic and functional recovery –Overall, most patients with prompt hospitalization and respiratory care can expect a complete or nearly complete recovery with return to previous level of functioning. Long-term morbidity is low in patients with mild disease, with complete resolution of symptoms generally occurring within the first three months. In comparison, patients with severe disease may experience protracted courses involving years of neurologic deficits, sequelae from extended mechanical ventilation, and nosocomial illness.

The largest reported experience on the long-term outcomes after acute paralytic botulism comes from a case-control study of 217 patients in the Republic of Georgia and three randomly selected community controls for each patient [87]. During the initial infection, 15 percent had been hospitalized for at least one month, and 25 percent required mechanical ventilation. At a median of 4.3 years, botulism survivors were more likely to report their current health as fair or poor (68 versus 17 percent, odds ratio [OR] 5) and worse compared with six years prior (68 versus 17 percent, OR 18). Botulism survivors were also more likely to report fatigue, weakness, dizziness, difficulty breathing with moderate exertion, and impaired psychosocial well-being. Requirement for mechanical ventilation during the acute illness and older age were independent predictors of worse long-term health.

●Mortality – With prompt attention to the impending respiratory failure and supportive care, mortality in botulism ranges from less than 5 percent to 8 percent (including infants) [58,88]; since 1980, the case-fatality rate has been ≤4 percent among patients with foodborne botulism in the United States [17]. The mortality rate for infant botulism, the most common form in the United States, is less than 1 percent [89]. Initial misdiagnosis and disease caused by toxin type A are both associated with fatal outcomes [17].

A retrospective review of 706 patients hospitalized for foodborne botulism in the Republic of Georgia, which has the highest reported rate of foodborne botulism in the world, suggested that the prognosis can be estimated based upon the manifestations of the disease [58]:

•Shortness of breath alone identified patients at increased mortality risk (18 versus 1 percent without this symptom). In addition, shortness of breath was present in 50 of the 54 patients who died.

•In comparison, there were no deaths among 209 patients without shortness of breath, facial muscle weakness, or vomiting.

Prospective validation of these observations is necessary.

SUMMARY AND RECOMMENDATIONS

●Microbiology – Botulism is a rare but potentially life-threatening neuroparalytic syndrome caused by a neurotoxin produced by Clostridium botulinum, a heterogeneous group of gram-positive, rod-shaped, spore-forming, obligate anaerobic bacteria. They are ubiquitous, easily isolated from the surfaces of vegetables, fruits, and seafood, and exist in soil and marine sediment worldwide. (See 'Introduction' above and 'Microbiology and pathogenesis' above.)

●Types – Several forms of botulism exist. The most common are infant botulism, foodborne botulism, and wound botulism. (See 'Types of botulism and their sources' above.)

•Infant botulism occurs when C. botulinum spores are ingested, colonize the host's gastrointestinal (GI) tract, and release toxin produced in vivo; this can rarely occur in adults (adult intestinal colonization botulism). (See 'Infant botulism' above and "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism'.)

•Foodborne botulism is caused by ingestion of food contaminated with preformed botulinum toxin; it is typically associated with home-canned or fermented foods. (See 'Foodborne botulism' above.)

•Wound botulism occurs when C. botulinum infects wounds and elaborates toxin. It is associated with injection drug use, particularly with "black tar" heroin use and subcutaneous or intramuscular injection. (See 'Wound botulism' above.)

●Clinical features – Botulism is classically described as the acute onset of bilateral cranial neuropathies associated with symmetric descending weakness. Other key features include absence of fever, maintenance of alertness, and lack of sensory deficits other than blurred vision. Nonspecific GI symptoms may also be seen, particularly with foodborne botulism. (See 'Clinical manifestations' above.)

●Clinical suspicion and presumptive diagnosis – The possibility of botulism should be considered in patients with acute onset of signs and symptoms suggesting cranial nerve abnormalities, particularly if they are afebrile (table 1), and in infants with acute onset of weak suck, ptosis, inactivity, and constipation (eg, floppy baby syndrome). A careful history and physical examination are essential to the presumptive diagnosis of botulism, which can be made on clinical findings of a cranial neuropathy with symmetric descending paralysis without a sensory neuropathy. Suspected food sources should be retained for investigation. (See 'When to consider the possibility of botulism' above.)

●Contacting public health officials – In the United States, clinicians caring for patients with suspected botulism should contact the state health department immediately for assistance with laboratory evaluation and management. After hours, regional poison centers (1-800-222-1222) can help contact on-call state health department representatives.

•State public health officials can reach the United States Centers for Disease Control and Prevention (CDC) clinical emergency botulism service at 770-488-7100.

•For suspected infant botulism occurring in any state, the California Department of Health Services’ Infant Botulism Treatment and Prevention Program should be contacted (www.infantbotulism.org or 510-231-7600).

●Confirming the diagnosis – This is done through identifying toxin in serum, stool, vomitus, or food sources or isolating C. botulinum from stool, wound specimens, or food sources. Specimens should be collected as soon as possible because toxin levels decrease over time; additionally, serum and gastric specimens should be collected prior to antitoxin administration. However, the decision to administer antitoxin should be based on the presumptive clinical diagnosis of botulism and not be delayed while awaiting results of confirmatory diagnostic studies. (See 'Confirming the diagnosis' above.)

●Hospitalization and monitoring – Any patient with clinical signs, symptoms, or history suspicious for botulism should be hospitalized and monitored for progressive weakness and signs of respiratory failure that warrant intubation. (See 'Supportive/respiratory care and monitoring' above.)

●Antitoxin – Antitoxin is the main therapeutic option for botulism. For patients with confirmed or highly suspected botulism, we recommend prompt administration of botulinum antitoxin (BAT) (Grade 1B). In the United States, equine serum heptavalent BAT is used to treat non-infant botulism; human-derived botulism immune globulin is used for infant botulism. Antitoxin is obtained through state health departments. (See 'Botulinum antitoxin (BAT) for non-infant botulism' above and "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism'.)

●Limited role for antibiotics – Antibiotics to treat C. botulinum have no demonstrated benefit and have theoretical harm in patients with botulism, and they are not generally warranted. When antibiotics are used to treat concurrent infections (eg, wound infection, abscess, pneumonia), agents that potentiate neuromuscular blockade, such as aminoglycosides, tetracyclines, clindamycin, and polymyxins, should be avoided. (See 'Wound management' above and "Acute cellulitis and erysipelas in adults: Treatment".)

●Prevention – Since most cases of botulism are acquired through food ingestion, the most critical aspect of botulism prevention is proper food handling and preparation. Good home-canning techniques will destroy spores. Infants <12 months of age should not ingest honey. The most important measure for the prevention of wound botulism is prompt medical management of infected wounds. (See 'Prevention' above.)

ACKNOWLEDGMENT — UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.