(See also Overview of Anaerobic Bacteria Overview of Anaerobic Bacteria Bacteria can be classified by their need and tolerance for oxygen: Facultative: Grow aerobically or anaerobically in the presence or absence of oxygen Microaerophilic: Require a low oxygen concentration... read more and Overview of Clostridial Infections Overview of Clostridial Infections Clostridia are spore-forming, gram-positive, anaerobic bacilli present widely in dust, soil, and vegetation and as normal flora in mammalian gastrointestinal tracts. Pathogenic species produce... read more .)
Tetanus bacilli form durable spores that occur in soil and animal feces and remain viable for years.
Worldwide, tetanus is estimated to cause over 200,000 deaths annually, mostly in neonates and young children, but the disease is so rarely reported that all figures are only rough estimates. In the US, 264 cases of tetanus and 19 deaths were reported from 2009 to 2017. Age distribution for cases was 23% in people ≥ 65 years, 64% in people aged 20 to 64 years, and 13% in people < 20 years, including 3 cases of tetanus neonatorum; all tetanus-related deaths occurred in people > 55 years ( 1 General reference Tetanus is acute poisoning from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for the name... read more ).
Disease incidence is directly related to the immunization level in a population, attesting to the effectiveness of preventive efforts. In the US, immunity levels tend to be lower in older age groups.
Patients with burns, surgical wounds, or a history of injection drug abuse are especially prone to developing tetanus. However, tetanus may follow trivial or even inapparent wounds. Infection may also develop postpartum in the uterus (maternal tetanus) and in a neonate's umbilicus (tetanus neonatorum) as a result of unsanitary delivery and umbilical cord care practices. Diabetes and a history of immunosuppression may be risk factors for tetanus.
1. Faulkner A, Tiwari T: Chapter 16: Tetanus. In Manual for the Surveillance of Vaccine-Preventable Diseases, edited by SW Roush, LM Baldy, MA Kirkconnell Hall. Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases. Page last reviewed: 02/06/2020.
Pathophysiology of Tetanus
C. tetani spores usually enter through contaminated wounds. Manifestations of tetanus are caused by an exotoxin (tetanospasmin) produced when bacteria lyse. The toxin enters peripheral nerve endings, binds there irreversibly, then travels retrograde along the axons and synapses, and ultimately enters the central nervous system (CNS). As a result, release of inhibitory transmitters from nerve terminals is blocked, thereby causing unopposed muscle stimulation by acetylcholine and generalized tonic spasticity, usually with superimposed intermittent tonic seizures. Disinhibition of autonomic neurons and loss of control of adrenal catecholamine release cause autonomic instability and a hypersympathetic state. Once bound, the toxin cannot be neutralized.
Most often, tetanus is generalized, affecting skeletal muscles throughout the body. However, tetanus is sometimes localized to muscles near an entry wound.
Pearls & Pitfalls
Symptoms and Signs of Tetanus
The incubation period ranges from 2 to 50 days (average, 5 to 10 days). Symptoms of tetanus include
Jaw stiffness (most frequent)
Stiff neck, arms, or legs
Arching of the back (opisthotonos)
Later, patients have difficulty opening their jaw (trismus).
Facial muscle spasm produces a characteristic expression with a fixed smile and elevated eyebrows (risus sardonicus). Rigidity or spasm of abdominal, neck, and back muscles and sometimes opisthotonos (generalized rigidity of the body with arching of the back and neck) may occur. Sphincter spasm causes urinary retention or constipation. Dysphagia may interfere with nutrition.
Characteristic painful, generalized tonic spasms with profuse sweating are precipitated by minor disturbances such as a draft, noise, or movement. Mental status is usually clear, but coma may follow repeated spasms. During generalized spasms, patients are unable to speak or cry out because of chest wall rigidity or glottal spasm. Rarely, fractures result from sustained spasms.
Spasms also interfere with respiration, causing cyanosis or fatal asphyxia.
Temperature is only moderately elevated unless a complicating infection, such as pneumonia, is present. Respiratory and pulse rates are increased. Reflexes are often exaggerated. Protracted tetanus may manifest as a very labile and overactive sympathetic nervous system, including periods of hypertension, tachycardia, and myocardial irritability.
Causes of death
Respiratory failure is the most common cause of death. Laryngeal spasm and rigidity and spasms of the abdominal wall, diaphragm, and chest wall muscles cause asphyxiation. Hypoxemia can also induce cardiac arrest, and pharyngeal spasm leads to aspiration of oral secretions with subsequent pneumonia, contributing to a hypoxemic death. Pulmonary embolism is also possible. However, the immediate cause of death may not be apparent.
In localized tetanus, there is spasticity of muscles near the entry wound but no trismus; spasticity may persist for weeks.
Cephalic tetanus is a form of localized tetanus that affects the cranial nerves. It is more common among children; in them, it may occur with chronic otitis media or may follow a head wound. Incidence is highest in Africa and India. All cranial nerves can be involved, especially the 7th. Cephalic tetanus may become generalized.
Tetanus in neonates is usually generalized and frequently fatal. It often begins in an inadequately cleansed umbilical stump in children born of inadequately immunized mothers. Onset during the first 2 weeks of life is characterized by rigidity, spasms, and poor feeding. Bilateral deafness may occur in surviving children.
Diagnosis of Tetanus
Tetanus should be considered when patients have sudden, unexplained muscle stiffness or spasms, particularly if they have a history of a recent wound or risk factors for tetanus.
Tetanus can be confused with meningoencephalitis of bacterial or viral origin, but the following combination suggests tetanus:
An intact sensorium
Normal cerebrospinal fluid
Trismus must be distinguished from peritonsillar or retropharyngeal abscess or another local cause. Phenothiazines can induce tetanus-like rigidity (eg, dystonic reaction, neuroleptic malignant syndrome).
C. tetani can sometimes be cultured from the wound, but culture is not sensitive; only 30% of patients with tetanus have positive cultures. Also, false-positive cultures can occur in patients without tetanus.
Prognosis for Tetanus
Tetanus has a mortality rate of
In untreated adults: 15 to 60%
In neonates, even if treated: 80 to 90%
Mortality is highest at the extremes of age and in drug abusers.
The prognosis is poorer if the incubation period is short and symptoms progress rapidly or if treatment is delayed. The course tends to be milder when there is no demonstrable focus of infection.
With use of modern supportive care, most patients recover.
Treatment of Tetanus
Supportive care, particularly respiratory support
Benzodiazepines for muscle spasms
Metronidazole or penicillin
Sometimes drugs for autonomic dysfunction
Treatment of tetanus requires maintaining adequate ventilation. Additional interventions include early and adequate use of human tetanus immune globulin (TIG) to neutralize nonfixed toxin; prevention of further toxin production; sedation; control of muscle spasm, hypertonicity, fluid balance, and intercurrent infection; and continuous nursing care. IV immune globulin (IVIG), which contains tetanus antitoxin, may be used if TIG is not available.
The patient should be kept in a quiet room. Several principles should guide all therapeutic interventions:
Prevent further toxin release by debriding the wound and giving an antibiotic Antibiotics Tetanus is acute poisoning from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for the name... read more
Neutralize unbound toxin outside the CNS with human tetanus immune globulin
Immunize using tetanus toxoid, taking care to inject it into a different body site than the antitoxin
Minimize the effect of toxin already in the CNS
Because dirt and dead tissue promote C. tetani growth, prompt, thorough debridement, especially of deep puncture wounds, is essential. Antibiotics are not substitutes for adequate debridement and immunization but typically are given.
Antitoxin and toxoid
The benefit of human-derived antitoxin depends on how much tetanospasmin is already bound to the synaptic membranes—only free toxin is neutralized. For adults, human TIG 3000 to 6000 units IM is given once; this large volume may be split and given at separate sites around the wound. Dose can range from 500 to 6000 units, depending on wound severity, but some authorities feel that 500 units are adequate.
Antitoxin of animal origin is far less preferable because it does not maintain the patient’s serum antitoxin level well and risk of serum sickness is considerable. If horse serum must be used, the usual dose is 50,000 units IM or IV (CAUTION: See Skin testing Skin testing ).
If necessary, IVIG or antitoxin can be injected directly into the wound, but this injection is not as important as good wound care.
Tetanus infection does not confer immunity, so unless their vaccination history indicates completion of a full primary series, patients should receive a full primary tetanus vaccination series using an age-appropriate preparation (see Prevention Prevention Tetanus is acute poisoning from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for the name... read more below). Antitoxin and vaccine should be injected into different body sites to avoid neutralizing the vaccine.
Management of muscle spasm
Drugs are used to manage spasms.
Benzodiazepines are the standard of care to control rigidity and spasms. They block reuptake of an endogenous inhibiting neurotransmitter, gamma-aminobutyric acid (GABA), at the GABAA receptor.
Diazepam can help control seizures, counter muscle rigidity, and induce sedation. Dosage varies and requires meticulous titration and close observation. The most severe cases may require 10 to 30 mg IV every 1 to 4 hours. Less severe cases can be controlled with 5 to 10 mg orally every 2 to 4 hours. Dosage varies by age:
Children > 30 days and < 5 years: 1 to 2 mg IV given slowly or IM, repeated every 3 to 4 hours as necessary
Children ≥ 5 years: 5 to 10 mg IV or IM every 3 to 4 hours
Adolescents: 5 mg IV, repeated every 2 to 6 hours as needed (high doses may be required)
Adults: 5 to 10 mg IV every 4 to 6 hours, increased as needed up to 40 mg/hour IV drip
Diazepam has been used most extensively, but midazolam (adults, 0.1 to 0.3 mg/kg/hour IV infusion; children, 0.06 to 0.15 mg/kg/hour IV infusion) is water soluble and preferred for prolonged therapy. Midazolam reduces risk of lactic acidosis due to propylene glycol solvent, which is required for diazepam and lorazepam, and reduces risk of long-acting metabolites accumulating and causing coma.
Benzodiazepines may not prevent reflex spasms, and effective respiration may require neuromuscular blockade with vecuronium 0.1 mg/kg IV or other paralytic drugs and mechanical ventilation. Pancuronium has been used but may worsen autonomic instability. Vecuronium is free of adverse cardiovascular effects but is short-acting. Longer-acting drugs (eg, pipecuronium, rocuronium) also work, but no randomized clinical comparative trials have been done.
Intrathecal baclofen (a GABAA agonist) is effective but has no clear advantage over benzodiazepines. It is given by continuous infusion; effective doses range between 20 and 2000 mcg/day. A test dose of 50 mcg is given first; if response is inadequate, 75 mcg may be given 24 hours later, and 100 mcg may be given 24 hours after that. Patients who do not respond to 100 mcg are not candidates for chronic infusion. Coma and respiratory depression requiring ventilatory support are potential adverse effects.
Dantrolene (loading dose 1.0 to 1.5 mg/kg IV, followed by infusion of 0.5 to 1.0 mg/kg every 4 to 6 hours for ≤ 25 days) relieves muscle spasticity. Dantrolene given orally can be used in place of infusion therapy for up to 60 days. Hepatotoxicity and expense limit its use.
Management of autonomic dysfunction
Morphine may be given every 4 to 6 hours to control autonomic dysfunction, especially cardiovascular; total daily dose is 20 to 180 mg.
Beta-blockade is used to control episodes of hypertension and tachycardia, but use of long-acting drugs such as propranolol is not recommended. Sudden cardiac death is a feature of tetanus, and beta-blockade can increase risk; however, esmolol, a short-acting beta-blocker, has been used successfully. IV atropine has been used at high doses; blockade of the parasympathetic nervous system markedly reduces excessive sweating and secretions. Lower mortality has been reported in clonidine-treated patients than in those treated with conventional therapy.
Magnesium sulfate at doses that maintain serum levels between 4 to 8 mEq/L (eg, 4 g bolus followed by 2 to 3 g/hour by IV continuous infusion) has a stabilizing effect, eliminating catecholamine stimulation. Patellar tendon reflex is used to assess overdosage. Tidal volume may be impaired, so ventilatory support must be available.
Other drugs that may prove useful include
Pyridoxine (100 mg once/day), which lowers mortality in neonates
Sodium valproate, which blocks GABA-aminotransferase, inhibiting GABA catabolism
Angiotensin-converting enzyme inhibitors, which inhibit angiotensin II and reduce norepinephrine release from nerve endings
Dexmedetomidine (a potent alpha-2 adrenergic agonist)
Adenosine, which reduces presynaptic norepinephrine release and antagonizes the inotropic effect of catecholamines
Corticosteroids are of unproven benefit; their use is not recommended.
The role of antibiotic therapy is minor compared with wound debridement and general support. Typical antibiotics include penicillin G 6 million units IV every 6 hours, doxycycline 100 mg IV 2 times a day, and metronidazole 500 mg IV every 6 to 8 hours.
In moderate or severe cases, patients should be intubated. Mechanical ventilation is essential when neuromuscular blockade is required to control muscle spasms that impair respirations.
IV hyperalimentation avoids the hazard of aspiration secondary to gastric tube feeding. Because constipation is usual, stools should be kept soft. A rectal tube may control distention. Bladder catheterization is required if urinary retention occurs.
Chest physiotherapy, frequent turning, and forced coughing are essential to prevent pneumonia. Analgesia with opioids is often needed.
Prevention of Tetanus
A primary series of tetanus vaccinations followed by regular boosters is required. Children < 7 years require 5 primary vaccinations, and unimmunized patients > 7 years require 3. The vaccine may be tetanus toxoid alone (TT), but toxoid is typically combined with diphtheria and/or pertussis. Children's vaccines have higher doses of the diphtheria and pertussis components (DTaP, DT) than adults' vaccines (Tdap, Td).
Children are given DTaP Diphtheria-Tetanus-Pertussis Vaccine Vaccines that contain diphtheria toxoid, tetanus toxoid, and acellular pertussis help protect against diphtheria, tetanus, and pertussis, but they do not prevent all cases. For more information... read more at ages 2 months, 4 months, 6 months, 15 to 18 months, and 4 to 6 years; they should get a Tdap booster at age 11 to 12 years, and Td every 10 years thereafter (see table Recommended Immunization Schedule for Ages 0–6 Years Recommended Immunization Schedule for Ages 0–6 Years and table Recommended Immunization Schedule for Ages 7–18 Years Recommended Immunization Schedule for Ages 7–18 Years ).
Unimmunized adults are given Tdap Tetanus-Diphtheria Vaccine A vaccine for tetanus alone is available, but the tetanus vaccine is typically combined with those for diphtheria and/or pertussis. The vaccine for diphtheria is available only in combination... read more initially, then Td 4 weeks and 6 to 12 months later, and Td every 10 years thereafter. Adults who have not had a vaccine that contains pertussis should be given a single dose of Tdap instead of one of the Td boosters. Adults ≥ 65 who anticipate close contact with an infant < 12 months and who have not previously received Tdap should be given a single dose of Tdap.
Pregnant women should be given Tdap during each pregnancy, preferably at 27 to 36 weeks gestation, regardless of when they were last vaccinated; the fetus can develop passive immunity from vaccines given at this time.
For routine diphtheria, tetanus, and pertussis immunization and booster recommendations, see Diphtheria-Tetanus-Pertussis Vaccine Diphtheria-Tetanus-Pertussis Vaccine Vaccines that contain diphtheria toxoid, tetanus toxoid, and acellular pertussis help protect against diphtheria, tetanus, and pertussis, but they do not prevent all cases. For more information... read more and Tetanus-Diphtheria Vaccine Tetanus-Diphtheria Vaccine A vaccine for tetanus alone is available, but the tetanus vaccine is typically combined with those for diphtheria and/or pertussis. The vaccine for diphtheria is available only in combination... read more .
After injury, tetanus vaccination is given depending on wound type and vaccination history; tetanus immune globulin may also be indicated (see table Tetanus Prophylaxis in Routine Wound Management Tetanus Prophylaxis in Routine Wound Management ). Patients not previously vaccinated are given a 2nd and 3rd dose of toxoid at monthly intervals.
Because tetanus infection does not confer immunity, patients who have recovered from clinical tetanus should be vaccinated unless they have completed a full primary series.
Tetanus Prophylaxis in Routine Wound Management
History of Adsorbed Tetanus Toxoid
Clean, Minor Wounds
All Other Wounds*
Unknown or < 3 doses
≥ 3 doses
Yes if > 10 years since last dose
Yes if > 5 years since last dose
* Such as (but not limited to) wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; crush injuries; avulsions; and wounds resulting from missiles, burns, or frostbite.
† For patients ≥ 10 years who have not previously received a dose of Tdap, a single dose of Tdap should be given instead of one Td booster. Children < 7 years should be given DTaP or, if pertussis vaccine is contraindicated, DT. Children aged 7–9 years should be given Td.
‡ TIG 250–500 units IM. People with HIV infection or severe immunodeficiency who have contaminated wounds (including minor wounds) should also receive TIG, regardless of their history of tetanus immunizations.
DT = diphtheria and tetanus toxoids (for children); DTaP = diphtheria and tetanus toxoids, acellular pertussis (for children); Td = tetanus and diphtheria toxoids adsorbed (for adults); Tdap = tetanus and diphtheria toxoids, acellular pertussis (for adults); TIG = tetanus immune globulin (human).
Tetanus is caused by a toxin produced by Clostridium tetani in contaminated wounds.
Tetanus toxin blocks release of inhibitory neurotransmitters, causing generalized muscle stiffness with intermittent spasms; seizures and autonomic instability may occur.
Mortality is 15 to 60% in untreated adults and 80 to 90% in neonates even if treated.
Prevent further toxin release by debriding the wound and giving an antibiotic (eg, penicillin, doxycycline), and neutralize unbound toxin with human tetanus immune globulin.
Give IV benzodiazepines for muscle spasm, and use neuromuscular blockade and mechanical ventilation as needed for respiratory insufficiency due to muscle spasm.
Prevent tetanus by following routine immunization recommendations.
Drugs Mentioned In This Article
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