Tetanus

Background

Tetanus is characterized by an acute onset of hypertonia, painful muscular contractions (usually of the muscles of the jaw and neck), and generalized muscle spasms without other apparent medical causes. Despite widespread immunization of infants and children since the 1940s, tetanus still occurs in the United States.^[1]  Tetanus primarily affects older adults because of their higher rate of being unvaccinated or inadequately vaccinated.^[2]  The image below illustrates tetanus cases in the United States from 1947-2023.

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Reported number of tetanus cases in the United States from 1947-2023. Image from National Notifiable Disease Surveillance System (NNDSS), Centers for ....

Tetanus may be categorized into the following 4 clinical types^[1] :

• Generalized tetanus
• Localized tetanus
• Cephalic tetanus
• Neonatal tetanus

Approximately 50-75% of patients with generalized tetanus present with trismus (“lockjaw”), which is the inability to open the mouth secondary to masseter muscle spasm. Nuchal rigidity and dysphagia also are early complaints that cause risus sardonicus, the scornful smile of tetanus, resulting from facial muscle involvement.^{[3, 4]}

As the disease progresses, patients have generalized muscle rigidity with intermittent reflex spasms in response to stimuli (eg, noise, touch). Tonic contractions cause opisthotonos (ie, flexion and adduction of the arms, clenching of the fists, and extension of the lower extremities). During these episodes, patients have an intact sensorium and feel severe pain. The spasms can cause fractures, tendon ruptures, and acute respiratory failure.

Patients with localized tetanus present with persistent rigidity in the muscle group close to the injury site.^[1] The muscular rigidity is caused by a dysfunction in the interneurons that inhibit the alpha motor neurons of the affected muscles. No further central nervous system (CNS) involvement occurs in this form, and mortality is very low.

Cephalic tetanus is uncommon and usually occurs after head trauma or otitis media. Patients with this form present with cranial nerve (CN) palsies. The infection may be localized or may become generalized.^[5]

Neonatal tetanus (tetanus neonatorum) is a major cause of infant mortality in underdeveloped countries but is rare in the United States. Infection results from umbilical cord contamination during unsanitary delivery, coupled with a lack of maternal immunization. At the end of the first week of life, infected infants become irritable, feed poorly, and develop rigidity with spasms. Neonatal tetanus has a very poor prognosis.^{[6, 7]}

Although tetanus is quite rare, early diagnosis and intervention are lifesaving. Prevention is the ultimate management strategy for tetanus.

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Pathophysiology

Clostridium tetani is an obligate, anaerobic, motile, gram-positive bacillus.^[1]  It is nonencapsulated and forms spores that are resistant to heat, desiccation, and disinfectants. Since the colorless spores are located at one end of the bacillus, they cause the organism to resemble a turkey leg. They are found in soil, house dust, animal intestines, and human feces. Spores can persist in normal tissue for months to years.

To germinate, the spores require specific anaerobic conditions,^[8] such as wounds with low oxidation-reduction potential (eg, dead or devitalized tissue, foreign body, active infection). Under these conditions, upon germination, they may release their toxin. Infection by C tetani results in a benign appearance at the portal of entry because of the inability of the organism to evoke an inflammatory reaction unless coinfection with other organisms develops.

When the proper anaerobic conditions are present, the spores germinate and produce the following 2 toxins:

• Tetanolysin – This substance is a hemolysin with no recognized pathologic activity
• Tetanospasmin – This toxin is responsible for the clinical manifestations of tetanus^[9] ; by weight, it is one of the most potent toxins known, with an estimated minimum lethal dose of 2.5 ng/kg body weight

Tetanospasmin is synthesized as a 150-kd protein consisting of a 100-kd heavy chain and a 50-kd light chain joined by a disulfide bond.^[10] The heavy chain mediates binding of tetanospasmin to the presynaptic motor neuron and also creates a pore for the entry of the light chain into the cytosol. The light chain is a zinc-dependent protease that cleaves synaptobrevin.^[1]

After the light chain enters the motor neuron, it travels by retrograde axonal transport from the contaminated site to the spinal cord in 2-14 days. When the toxin reaches the spinal cord, it enters central inhibitory neurons. The light chain cleaves the protein synaptobrevin, which is integral to the binding of neurotransmitter containing vesicles to the cell membrane.

As a result, gamma-aminobutyric acid (GABA)-containing and glycine-containing vesicles are not released, and there is a loss of inhibitory action on motor and autonomic neurons.^[11] With this loss of central inhibition, there is autonomic hyperactivity as well as uncontrolled muscle contractions (spasms) in response to normal stimuli such as noises or lights.

Once the toxin becomes fixed to neurons, it cannot be neutralized with antitoxin. Recovery of nerve function from tetanus toxins requires sprouting of new nerve terminals and formation of new synapses.

Localized tetanus develops when only the nerves supplying the affected muscle are involved. Generalized tetanus develops when the toxin released at the wound spreads through the lymphatics and blood to multiple nerve terminals. The blood-brain barrier prevents direct entry of toxin to the CNS.

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Etiology

Tetanus is caused by the active toxin-producing bacillus form of Clostridium tetani. Spores of C tetani are ubiquitous in the environment and can survive for years.^[12]  These spores are resistant to many forms of decontamination, but can convert to tetanus bacilli under the appropriate anaerobic conditions, at which point they produce tetanus toxins. Infection most commonly occurs due to wound contamination with spores, even from wounds where medical attention was not deemed necessary.^[9]  Cases have been documented without obvious wounds of sites for infection. Childbirth is a significant cause of tetanus infection in the developing world.^[12]  Moreover, injection drug use has been linked to disease clusters in the United States.^[13]  Chronic wounds, such as venous or diabetic foot ulcers, also have been associated with cases of tetanus.^[14]

Underimmunization is an important cause of tetanus.^[2] Tetanus affects nonimmunized persons, partially immunized persons, or fully immunized individuals who do not maintain adequate immunity with periodic booster doses. Only 12-14% of patients with tetanus in the United States have received a primary series of tetanus toxoid. During 2001-2008, 10% of all patients with tetanus were known to be current with tetanus immunization, with only 1 death among this group. Surveillance data from 1998-2000 revealed the following^[13] :

• In 73% of patients with tetanus in the United States, tetanus occurred after an acute injury, including puncture wounds (50%), lacerations (33%), and abrasions (9%)
• Stepping on a nail accounted for 32% of the puncture wounds
• Tetanus was found to occur in burn victims; in patients receiving intramuscular injections; in persons obtaining a tattoo; and in persons with frostbite, dental infections (eg, periodontal abscesses), penetrating eye injuries, and umbilical stump infections
• Other reported risk factors included diabetes, chronic wounds (eg, skin ulcers, abscesses, or gangrene), parenteral drug abuse, and recent surgery (4% of US cases)
• During 1998-2000, 12% of patients with tetanus in the United States had diabetes (with mortality, 31%), compared with 2% during 1995-1997; of these patients, 69% had acute injuries and 25% had gangrene or a diabetic ulcer
• The median time interval between surgery and onset of tetanus was 7 days
• Tetanus was reported after tooth extractions, root canal therapy, and intraoral soft tissue trauma

Worldwide risk factors for neonatal tetanus include the following^[12] :

• Use of inadequately-sterilized instruments or contaminated dressings
• Unvaccinated mother
• Lack of hand cleansing by provider prior to delivery

Immunity from tetanus decreases with advancing age.^[15] Serologic testing for immunity has revealed a low level among elderly individuals in the United States. Approximately 50% of adults older than 50 years are nonimmune because they never were vaccinated or do not receive appropriate booster doses. The prevalence of immunity to tetanus in the United States exceeds 80% for persons aged 6-39 years but is only 28% for those older than 70 years.

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Epidemiology

United States statistics

Because of the widespread use of tetanus immunizations, the reported incidence of tetanus in the United States has declined substantially since the mid 1940s.^[16]

From 2001-2008, 233 cases of tetanus were reported in the United States, a 95% reduction since 1947. Deaths from the disease had decreased by 99% since that year. The case mortality rate was 13.2%. Tetanus cases among Hispanic individuals were approximately twice that among non-Hispanic persons, attributed to an increased rate of injection drug use among Hispanic patients. In the group of patients with known vaccination status, 40.2% had received no doses of tetanus toxoid; 15.4% of 195 patients had diabetes; and 15.3% of 176 were intravenous drug users. In the 51 individuals with an acute wound in whom adequate information was available, 96.1% had not received appropriate prophylaxis.^[2]

By November 2024, 30 tetanus cases were reported in the United States via the National Notifiable Diseases Surveillance System for the calendar year, up from 15 total cases reported in 2023 (NNDSS).^[17]

All 50 states require that children be vaccinated before being admitted to public schools. More than 96% of children have received 3 or more diphtheria and tetanus toxoids plus pertussis (DTP) vaccinations by the time they begin school.^[18]

In 2022, vaccination uptake by age 14 years among adolescents born in 2008 continued to fall behind that of earlier birth cohorts and differed according to sociodemographic factors and access to healthcare compared with that among earlier birth cohorts.^[19]

Vaccination uptake by age 13 years among those born in 2009 was similar to coverage estimates reported before the COVID-19 pandemic.

Among individuals aged 13-17 years, 2022 vaccination coverage levels were similar to 2021 levels. Coverage with at least 1 dose of tetanus, diphtheria, and acellular pertussis vaccine and at least 1 dose meningococcal conjugate vaccine was high and stable (around 90%). Healthcare providers should review adolescent vaccination records, especially those of adolescents born in 2008 as well as children and adolescents who are eligible for the Vaccines for Children program, to ensure all recommended vaccines are current.

Heroin users, particularly those who inject themselves subcutaneously, appear to be at high risk for tetanus. Quinine is used to dilute heroin and may support the growth of C tetani.^[20] The incidence of tetanus in people who use injection drugs increased 7.4% between 1991 and 1997, from 3.6% of all cases in 1991-1994 to 11% in 1995-1997. Injection drug users accounted for 15% of US tetanus cases from 1998 to 2000 (see the image below).^[13] Of the 19 people who used injection drugs and contracted tetanus in 1998-2000, only 1 reported an acute injury.

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Image from "Number of Tetanus Cases Reported Among Persons With Diabetes or Injection-Drug Use (IDU), by Age Group." Pascual FB, McGinley EL, Zanardi ....

From 1998-2000, 81% of cases in the United States were generalized tetanus, 17% were localized, and 2% were cephalic; 1 case of neonatal tetanus was reported.

The CDC has not published a tetanus surveillance summary for the United States since 2008, but continues to publish the number of reported cases by state through the National Notifiable Diseases Surveillance System.

International statistics

C tetani is found worldwide in soil, on inanimate objects, in animal feces, and, occasionally, in human feces. Tetanus is predominantly a disease of underdeveloped countries. It is common in areas where soil is cultivated, in rural areas, in warm climates, during summer months, and among males. In countries without a comprehensive immunization program, tetanus predominantly develops in neonates and young children.^{[21, 22]}

From 1990 to 2019, the incidence and death rate of tetanus fell significantly globally.^[23]

Developed nations have incidences of tetanus similar to those observed in the United States. For instance, only 126 cases of tetanus were reported in England and Wales from 1984-1992.^[24]  More recently, the UK reported only 4 cases of tetanus in England during 2022, down from 11 cases the previous year.^[25]

Although tetanus affects all ages, the highest prevalence is in newborns and young people.^[26]  The global burden of disease has fallen significantly since approximately 1990.^[23] Incidence has decreased from an estimated 615,000 cases globally in 1990 to about 74,000 in 2019. Additionally, annual deaths from tetanus fell from 275,000 to 35,000 in this same time period. Neonatal tetanus accounted for half of all cases of tetanus and in some areas was the predominant cause of neonatal mortality, with close to 100% case fatality rates depending on regional access to care. Since 2000, global rates of neonatal tetanus have declined 89%, although disruption of vaccination efforts during the COVID-19 pandemic has led to increased disease incidence in many countries.^[27]

Age-related demographics

Neonatal tetanus is rare in developed countries while accounting for a large burden of disease in resource-poor areas.^[23]

The risk for development of tetanus and for the most severe form of the disease in developed countries is highest in the elderly population. In the United States from 2001-2008, the incidence rate among patients aged 65 years or older was approximately 0.23 cases per 1 million population vs 0.08 cases per 1 million population for those younger than 65 years.^[2]  Moreover, the relative risk for fatal disease was about five times higher in patients older than 65 compared with those under 65 years. Patient older than 65 years accounted for 77% of deaths during this period.

Sex-related demographics

Tetanus affects both sexes. No overall predilection by sex has been reported, except to the extent that males may have more soil exposure in some cultures. In the United States from 1998 to 2000, the incidence of tetanus was 2.8 times higher in males aged 59 years and younger than in females in the same age range.^[13]

A difference in the levels of tetanus immunity exists between the sexes, with men being twice as likely to possess protective levels of antibodies compared with women.^[15] This is speculated to be because of additional vaccinations administered during military service or professional activities.

Race-related demographics

Tetanus affects all races. From 2001-2008, the incidence of tetanus in the United States was almost twice as high among Hispanic individuals compared with non-Hispanic persons (0.13 vs 0.07 cases per million population). Exclusion of patients with injection drug use showed nearly equal incidences at 0.08 vs 0.07 cases per million populations among Hispanics and non-Hispanics, respectively. Incidence also was similar among other identified racial groups including White Americans (0.08 per million population), African Americans (0.07), American Indian/Alaska natives (0.09), and Asian/Pacific Islanders (0.07).^[2]

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Prognosis

The prognosis is dependent on incubation period, the time from spore inoculation to first symptom, and the time from first symptom to first tetanic spasm.^[1]  The following statements typically hold true^[1] :

• In general, shorter intervals indicate more severe tetanus and a poorer prognosis
• Patients usually survive tetanus and return to their predisease state of health
• Recovery is slow and usually occurs over 2-4 months
• Some patients remain hypotonic
• Clinical tetanus does not produce a state of immunity; therefore, patients who survive the disease require active immunization with tetanus toxoid to prevent a recurrence

A rating scale has been developed for assessing the severity of tetanus and determining the prognosis. On this scale, 1 point is given for each of the following^[1] :

• Incubation period shorter than 7 days
• Period of onset shorter than 48 hours
• Tetanus acquired from burns, surgical wounds, compound fractures, septic abortion, umbilical stump, or intramuscular injection
• Narcotic addiction
• Generalized tetanus
• Temperature higher than 104°F (40°C)
• Tachycardia exceeding 120 beats/min (150 beats/min in neonates)

The total score indicates disease severity and prognosis as follows:

• 0 or 1 – Mild tetanus; mortality below 10%
• 2 or 3 – Moderate tetanus; mortality of 10-20%
• 4 – Severe tetanus; mortality of 20-40%
• 5 or 6 – Very severe tetanus; mortality above 50%

Cephalic tetanus always is severe or very severe. Neonatal tetanus always is very severe.

The case-fatality ratio in the United States was 91% in 1947, 21-31% from 1982 to 1990, 11% from 1995 to 1997, 18% from 1998 to 2000, and 13.2% from 2001-2008.^{[2, 13]}  Mortality in mild and moderate tetanus is approximately 6%; for severe tetanus, it may be as high as 60%. Mortality in the United States resulting from generalized tetanus is 30% overall, 52% in patients older than 60 years, and 13% in patients younger than 60 years.

Mortality is substantially higher for people older than 65 years, with approximately 5 times the relative risk for death compared to cases in patients younger than 65 years.^[2] From 1998 to 2000, 75% of the deaths in the United States were in patients older than 60 years.^[13] In addition, mortality is notably higher for people who require mechanical ventilation (30%) than for those who do not (4%).

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Image from "Number of Tetanus Cases Reported, Average Annual Incidence Rates, and Survival Status of Patients, by Age Group." Pascual FB, McGinley EL,....

Clinical tetanus is less severe among patients who have received a primary series of tetanus toxoid sometime during their life than among patients who are inadequately vaccinated or unvaccinated.^[13] Mortality in the United States is 7% for individuals who had previously received at least 1 dose of tetanus vaccine versus 31% of those who were unvaccinated.^[2]

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Patient Education

The importance of childhood immunizations and boosters in adulthood must be stressed. Midwives and birth attendants in developing and underdeveloped countries should be given training in aseptic birthing procedures. The basics of wound care and first aid should be widely taught. Early recognition of symptoms and signs of localized tetanus and timely access to medical care are essential.

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History

Most cases of tetanus in the United States occur in patients with a history of underimmunization, either because they were never vaccinated or because they completed a primary series but have not had a booster in the preceding 10 years.^[2] From 2001-2008, among the 233 reported cases, only 92 had information on their tetanus toxoid (TT) vaccine available. Of these 92 cases, 41% had received no doses of TT vaccine, 28% received 1 dose, 5.4% received 3 doses, and 26% received 4 or more doses. Among 51 patients with documentation sufficient to assess prophylaxis after acute wounds, 96% received inadequate prophylaxis with TT vaccine (or vaccine plus tetanus immune globulin for those who are underimmunized or with unknown vaccine status) based on guidelines recommendations.

The incubation period can vary between 1-21 days with the majority of cases developing within 8 days.^[28] Cases with faster incubation are generally more severe in nature.

Patients sometimes remember an injury, but often, the injury goes unnoticed. Patients may report a sore throat with dysphagia (early sign). The initial manifestation may be local tetanus, in which the rigidity affects only 1 limb or area of the body where the clostridium-containing wound is located. Trismus (ie, lockjaw) is commonly the first presenting symptom.^[1]  Other presenting complaints include stiffness, neck rigidity, restlessness, and reflex spasms.

Subsequently, muscle rigidity becomes the major manifestation. Muscle rigidity spreads in a descending pattern from the jaw and facial muscles over the next 24-48 hours to the extensor muscles of the limbs.

Dysphagia occurs in moderately severe tetanus as a consequence of pharyngeal muscle spasms, and onset usually is insidious over several days. Reflex spasms develop in most patients and can be triggered by minimal external stimuli such as noise, light, or touch. The spasms last seconds to minutes; become more intense; increase in frequency with disease progression; and can cause apnea, fractures, dislocations, and rhabdomyolysis. Laryngeal spasms can occur at any time and can result in asphyxia.

Other symptoms include elevated temperature, sweating, elevated blood pressure, and episodic rapid heart rate.

Sustained contraction of facial musculature produces a sneering grin expression known as risus sardonicus.

Generalized tetanus

Generalized tetanus is the most commonly found form of tetanus in the United States, accounting for about 80% of cases.^[1]  The extent of the trauma varies from trivial injury to contaminated crush injury. The incubation period is 8 days on average, largely depending on the distance of the injury site from the central nervous system (CNS). Spasms can occur for 3-4 weeks with total recovery often requiring months.^[28]

Trismus is the presenting symptom in 75% of cases; a dentist or an oral surgeon often initially sees the patient. Other early features include irritability, restlessness, diaphoresis, and dysphagia with hydrophobia, drooling, and spasm of the back muscles. These early manifestations reflect involvement of bulbar and paraspinal muscles, possibly because these structures are innervated by the shortest axons. The condition may progress for 2 weeks despite antitoxin therapy because of the time needed for intra-axonal antitoxin transport.

Localized tetanus

Localized tetanus involves an extremity with a contaminated wound and is of highly variable severity. Persistent contraction of muscles in the local area of the injury are the characteristic feature, and can occur before the onset of generalized tetanus. Prognosis is excellent given the localized nature of the disease.^[28]

Cephalic tetanus

Cephalic tetanus generally follows head injury or develops with infection of the middle ear. It involves the cranial nerves, often in the facial area.^[28]  Patients may present with symptoms of cranial nerve palsies within 1-2 days of head or facial injury.^[1]

Neonatal tetanus

Neonatal tetanus (tetanus neonatorum) is generalized tetanus that results from infection of a neonate. It primarily occurs in underdeveloped countries and accounts for the majority of reported tetanus cases.^[12] The usual cause is the use of contaminated materials to sever or dress the umbilical cord in newborns of unimmunized mothers.

The usual incubation period after birth is 4-14 days, with an average of 7 days.^[1]  Afflicted newborns often first present with inability to suck, poor feeding, and excessive crying.^[12]

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Physical Examination

Common first signs of tetanus are headache and muscular stiffness in the jaw (ie, lockjaw), followed by neck stiffness, difficulty swallowing, rigidity of abdominal muscles, spasms, and sweating. Patients often are afebrile. Stimulation of the posterior pharyngeal wall may elicit reflex spasms of the masseter muscles that cause patients to bite down as opposed to gag (spatula test).^[29]

Severe tetanus results in opisthotonos, flexion of the arms, extension of the legs, periods of apnea resulting from spasm of the intercostal muscles and diaphragm, and rigidity of the abdominal wall.^[1]  Late in the disease, autonomic dysfunction develops, with hypertension and tachycardia alternating with hypotension and bradycardia; cardiac arrest may occur.

Population studies on tetanus patients in the United States have shown the lower extremity is the site of antecedent acute injury in 51% of patients, the upper extremity is the site of antecedent injury in 36% of patients, and the head or the trunk is the site of antecedent injury in 10% of patients, with the remaining 3% of patients having unreported wound locations.^[13]

Patients with tetanus may present with abdominal tenderness and guarding, mimicking an acute abdomen. Exploratory laparotomies have been performed before the correct diagnosis was apparent.^[1]

Tetanospasmin has a disinhibitory effect on the autonomic nervous system (ANS).^[30]  ANS disturbances (eg, sweating, fluctuating blood pressure, episodic tachydysrhythmia, and increased catecholamine release) are observed usually about a week after onset of motor symptoms. Drugs with beta-blocker effects have been used to control the cardiovascular manifestations of ANS instability, but they also have been associated with increased risk for sudden death.

Generalized tetanus

Sustained trismus may result in the characteristic sardonic smile (risus sardonicus) and persistent spasm of the back musculature may cause opisthotonos. Waves of opisthotonos are highly characteristic of the disease. With progression, the extremities become involved in episodes of painful flexion and adduction of the arms, clenched fists, and extension of the legs.

Noise or tactile stimuli may precipitate spasms and generalized convulsions. Involvement of the ANS may result in severe arrhythmias, oscillation of blood pressure, profound diaphoresis, hyperthermia, rhabdomyolysis, laryngeal spasm, and urinary retention. In most cases, the patient remains lucid.

Localized tetanus

In mild cases of localized tetanus, patients may have weakness of the involved extremity, presumably due to partial immunity; in more severe cases, they may have intense, painful spasms of the group of muscles in close proximity to the site of injury. This disorder may persist for several weeks but is usually self-limiting; however, more severe cases tend to progress to generalized tetanus.^[1]

Cephalic tetanus

Cephalic tetanus is characterized by variable CN palsies. Noticeable symptoms on physical exam may include neck stiffness, deviation of the eyes, risus sardonicus, or retraction of the eyelids.^[1]  Patients also may present with symptoms of generalized tetanus.

Neonatal tetanus

Neonatal tetanus presents with physical exam findings similar to generalized tetanus. Newborns may present with poor ability to suck or breastfeed, generalized spasms, or crying.^[12]

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Complications

Complications include spasm of the vocal cords and spasm of the respiratory muscles that cause interference with breathing.^[31] Patients experience severe pain during each spasm. During the spasm, the upper airway can be obstructed, or the diaphragm may participate in the general muscular contraction.

Autonomic dysfunction with cardiac arrythmias have been documented as a major cause of death in severe tetanus patient undergoing ICU care.^[32] Nosocomial infections also are common in this patient population. Secondary infections may include sepsis from decubitus ulcers, hospital-acquired pneumonia, and catheter-related infections.

Neonatal tetanus is associated with long-term sequalae including motor and sensory dysfunction.^[33]

Pulmonary embolism is another possible complication more commonly associated with users of injection drugs and the elderly.^[28]

Before 1954, asphyxia from tetanic spasms was the usual cause of death in patients with tetanus. However, with the advent of neuromuscular blockers, mechanical ventilation, and pharmacologic control of spasms, sudden cardiac death has become the leading cause of death.

Further complications include the following:

• Long bone fractures
• Glenohumeral joint and temporomandibular joint dislocations
• Hypoxic injury and aspiration pneumonia
• Clotting in the blood vessels of the lung
• Adverse effects of autonomic instability,^[34] including hypertension and cardiac dysrhythmias
• Paralytic ileus, pressure sores, and urinary retention
• Malnutrition and stress ulcers
• Coma, nerve palsies, neuropathies, psychological aftereffects, and flexion contractures

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Approach Considerations

Tetanus should be suspected in patients experiencing sudden, unexplained muscle stiffness or spasms, especially if they have a recent wound or risk factors for the disease.^[35] It can be mistaken for meningoencephalitis, but the presence of an intact sensorium, normal cerebrospinal fluid, and muscle spasms indicates tetanus. Trismus should be differentiated from local causes such as peritonsillar or retropharyngeal abscesses. Additionally, certain medications, such as phenothiazines, can cause tetanus-like rigidity.

Although Clostridium tetani can be cultured from wounds, the sensitivity is low, with only 30% of tetanus patients showing positive cultures, and false positives can occur in those without the disease.

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Laboratory Studies

No specific laboratory tests exist for determining the diagnosis of tetanus. The diagnosis is clinically based on the presence of trismus, dysphagia, generalized muscular rigidity, spasm, or combinations thereof.^[1] Although the laboratory findings are not diagnostically valuable, they may help exclude strychnine poisoning.

Blood counts and blood chemical findings are unremarkable.

Wound cultures are only positive for C tetani in 30% of cases and therefore generally are not useful clinically.^[28]  Moreover, cultures can be positive in patients without clinical tetanus symptoms.

A lumbar puncture is not necessary for diagnosis. Cerebrospinal fluid (CSF) findings are normal, except for an increased opening pressure, especially during spasms.

Assay for tetanus toxin antibodies do exist. However, their clinical utility in diagnosing acute tetatnus is limited. They are more commonly used for confirmation of tetanus immunity. Previous research has suggested that levels of serum antitoxin of 0.01 IU/mL or greater can be protective, although this is not always the case.^[1]

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Spatula Test

The spatula test is a simple diagnostic bedside test that involves touching the oropharynx with a spatula or tongue blade. In normal circumstances, it elicits a gag reflex, and the patient tries to expel the spatula (ie, a negative test result). If tetanus is present, patients develop a reflex spasm of the masseters and bite the spatula (ie, a positive test result).

In 400 patients, this test had a sensitivity of 94% and a specificity of 100%.^[29] No adverse sequelae (eg, laryngeal spasm) were reported.

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Other Studies

Electromyography (EMG) may show continuous discharge of motor subunits and shortening or absence of the silent interval normally observed after an action potential.^[36]

Nonspecific changes may be evident on electrocardiography (ECG).^[37]

No systematic studies have found diagnostically-significant findings on imaging.

While immunohistological testing has been reported for tetanus during autopsies,^[38]  there is no clinically-validated method for immunohistological diagnosis of tetanus for patients.

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Approach Considerations

The goals of treatment in patients with tetanus include the following^{[35, 39, 40]} :

• Initiating supportive therapy
• Debriding the wound to eradicate spores and alter conditions for germination
• Stopping the production of toxin within the wound
• Neutralizing unbound toxin
• Controlling disease manifestations
• Managing complications

Patients should be admitted to an intensive care unit (ICU). If the facility does not have an ICU, the patient should be transferred by critical care ambulance.

Passive immunization with human tetanus immune globulin (TIG) shortens the course of tetanus and may lessen its severity.^[40]  A dose of 500 U may be as effective as larger doses. Therapeutic TIG (3,000-6,000 units as 1 dose) also has been recommended for generalized tetanus. Other treatment measures include ventilatory support, high-calorie nutritional support, and pharmacologic agents that treat reflex muscle spasms, rigidity, tetanic seizures, and infections.

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Initial Supportive Therapy and Wound Care

Initial care includes administration of human tetanus immunoglobulin to bind circulating tetanus toxins.^{[1, 40]}  For more severe cases, ICU admission should be considered. Dark and quiet environments are recommended to prevent reflex spasms.^[9]  Wounds should be cleaned and debrided.

In moderate-to-severe presentations of tetanus, neuromuscular blocker therapy with intubation and mechanical ventilation should be considered.^{[32, 40]}  Tracheostomy also has been recommended due to the risk for reflex spasm during intubation.^[1]  As with most cases of prolonged ventilation, conversion to tracheostomy is recommended after 10 days of intubation if the patient will require continued ventilator support.^[41]

The possibility of developing tetanus directly correlates with the characteristics of the wound.^[1]  Recently acquired wounds with sharp edges that are well vascularized and not contaminated are least likely to develop tetanus. All other wounds are considered predisposed to tetanus. The most susceptible wounds are those that are grossly contaminated or that are caused by blunt trauma or bites. Wounds should be explored, carefully cleansed, and properly debrided. However, patients may develop tetanus without obvious wounds.^[9]

Early wound debridement generally is recommended.^[1] This can both remove spores and prevent germination in necrotic tissue. Debridement should take place after administration of antitoxin given the risk of releasing further tetanus toxin during the wound manipulation.

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Pharmacologic Therapy

Elimination of toxin production

Antimicrobials are used to decrease the number of vegetative forms of C tetani (the toxin source) in the wound.^[40] For years, penicillin G was used widely for this purpose, but it is not the drug of choice. Metronidazole (eg, 0.5 g every 6 hours) has comparable or better antimicrobial activity, and penicillin is a known antagonist of gamma-aminobutyric acid (GABA), as is tetanus toxin. Metronidazole also is associated with lower mortality.^[42]

Other antimicrobials that have been used are clindamycin, erythromycin, tetracycline, and vancomycin. Their role is not well established.

Neutralization of unbound toxin

Tetanus immune globulin (TIG) is recommended for treatment of tetanus.^[40] It should be kept in mind that TIG can only help remove unbound tetanus toxin; it cannot affect toxin bound to nerve endings. A single intramuscular (IM) dose of 250-500 units generally is recommended for children and adults, with part of the dose infiltrated around the wound if it can be identified.

The World Health Organization recommends TIG 250 units by IM injection or intravenously (IV)—depending on the available preparation—as soon as possible. For wounds older than 12 hours, wounds with extensive contamination, or patients heavier than 90 kg, 500 units IM is recommended instead. In addition, a single dose (0.5 mL) of the TT or Td vaccine is recommended either IM or deep subcutaneously for patients older than 10 years. For patients under 10 years of age, a single dose of the DT vaccine is recommended instead.^[43]  The CDC similarly recommends a 250 unit TIG dose IM for all patients with contaminated wounds and unknown or inadequate vaccination history.^[1]

Tetanus disease does not induce immunity; patients without a history of primary tetanus toxoid vaccination should receive a second dose 1-2 months after the first dose and a third dose 6-12 months later.

Control of disease manifestations

Benzodiazepines have emerged as the mainstay of symptomatic therapy for tetanus.^{[9, 40]}  Diazepam is the most frequently studied and used drug; it reduces anxiety, produces sedation, and relaxes muscles. Lorazepam is an effective alternative. High dosages of either may be required (up to 600 mg/day).^[9]

To prevent spasms that last longer than 5-10 seconds, administer diazepam IV, typically 10-40 mg every 1-8 hours. Vecuronium (by continuous infusion) or pancuronium (by intermittent injection) are adequate alternatives. Midazolam 5-15 mg/hr IV has been used. If the spasms are not controlled with benzodiazepines, long-term neuromuscular blockade is required.

Phenobarbital is another anticonvulsant that may be used to prolong the effects of diazepam. Phenobarbital also is used to treat severe muscle spasms and provide sedation when neuromuscular blocking agents are used. Other agents used for spasm control include baclofen, dantrolene, short-acting barbiturates, and chlorpromazine. Propofol has been suggested for sedation.^[44]

Intrathecal (IT) baclofen, a centrally acting muscle relaxant, has been used experimentally to wean patients off the ventilator and to stop diazepam infusion. IT baclofen is 600 times more potent than oral baclofen. Repeated IT injections have been efficacious in limiting duration of artificial ventilation or preventing intubation. Case reports and small case series have suggested that IT baclofen is effective in controlling muscle rigidity,^{[45, 46]} though others have questioned this.^[47]

The effects of baclofen begin within 1-2 hours and persist for 12-48 hours. The half-life elimination of baclofen in cerebrospinal fluid (CSF) ranges from 0.9 to 5 hours. After lumbar IT administration, the cervical-to-lumbar concentration ratio is 1:4. The major adverse effect is a depressed level of consciousness and respiratory compromise.

Management of complications

Specific therapy for autonomic system complications and control of spasms should be initiated.^[48] Magnesium sulfate can be used alone or in combination with benzodiazepines for this purpose. It should be given IV in a loading dose of 5 g (or 75 mg/kg), followed by continuous infusion at a rate of 2-3 g/h until spasm control is achieved.^[9]

The patellar reflex should be monitored; areflexia (absence of the patellar reflex) occurs at the upper end of the therapeutic range (4 mmol/L). If areflexia develops, the dosage should be reduced. An infusion of magnesium sulfate does not reduce the need for mechanical ventilation in adults with severe tetanus, but it does reduce the requirement for other drugs to control muscle spasms and cardiovascular instability.^[49]

A review of 3 controlled trials, 6 prospective, and 4 retrospective trials concluded that there is no mortality benefit to treatment of tetanus with magnesium sulfate. However, the average hospital stay and need for ventilator support was reduced with only a small incidence of magnesium toxicity.^[50]

Morphine is an option. Beta blockers have been recommended for management of autonomic dysfunction, but carry the risk for sudden cardiac death.^[30]

Hypotension requires fluid replacement and dopamine or norepinephrine administration. Parasympathetic overactivity is rare, but if bradycardia is sustained, a pacemaker may be needed. Clinical tetanus does not induce immunity against future attacks; therefore, all patients should be fully immunized with tetanus toxoid during the convalescent period.^[1]

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Diet and Activity

Maintenance of adequate nutrition is extremely important. Spasms can result in higher catabolism and metabolic needs.^[9]  Because of the risk for aspiration, patients should not be given any food by mouth. Nutrition should be provided to seriously ill patients via nasoduodenal tubes, gastrostomy tube feedings, or parenteral hyperalimentation. Consultation with a nutritionist is helpful.

The patient should be on bed rest in a room that can be kept dark and quiet. Even the slightest physical stimulus can cause a cycle of spasms.

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Consultations

An intensive care medicine specialist should be the primary physician coordinating the patient’s care. Consultations with the following specialists may be appropriate as the clinical situation dictates:

• Infectious diseases
• Toxicology - To help confirm or exclude strychnine toxicity as the cause of symptoms
• Neurology - To confirm or exclude seizures as a possible etiology of symptoms
• Pulmonary medicine – To be consulted after admission to the ICU for patients with severe respiratory symptoms or those requiring mechanical ventilation
• Anesthesiology – To be consulted after admission to the ICU if intrathecal baclofen is to be administered

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Prevention

For the latest vaccination recommendations, see CDC Immunization Schedules.^[51]

General recommendations ^[51]

During their October 2024 session, the Advisory Committee on Immunization Practices* (ACIP) endorsed the Recommended Immunization Schedule for Children and Adolescents up to 18 Years Old in the United States for the year 2025.^[58]  The "Special Situations" section has been updated to provide a summary of the guidelines for administering the tetanus and diphtheria vaccine (Td) to children under 7 years old who have a specific contraindication to the pertussis component of the DTaP vaccine.

In October 2024, the Advisory Committee on Immunization Practices (ACIP) approved the Recommended Immunization Schedule for Adults Ages 19 Years or Older, United States, 2025. Recommendations for routine vaccination now are described according to previous vaccination history.^[57]

Prevention of tetanus is accomplished through vaccination with DTP or DTaP at ages 2 months, 4 months, 6 months, 12-18 months, and 4-6 years.

Ages 11–18 years: A single dose of Tdap should be administered at the preventive care visit, ideally at ages 11–12 years. Following this, a booster dose of Td or Tdap is recommended every 10 years to maintain immunity against tetanus and diphtheria.

Ages ≥19 years: Individuals who have never received Tdap should receive 1 dose, regardless of the time since their last tetanus or diphtheria vaccine. Subsequent booster doses of Td or Tdap should be given every 10 years.

Pregnant individuals: It is recommended that pregnant people receive 1 dose of Tdap during each pregnancy, preferably between 27 and 36 weeks of gestation, regardless of their vaccination history.

Tetanus prophylaxis for wound management

A tetanus toxoid-containing vaccine is indicated if more than 5 years have passed since the last dose. For individuals aged ≥11 years who have not previously received Tdap or whose vaccination history is unknown, Tdap is preferred. Tetanus immunglobulin (TIG) is further recommended in patients with dirty wounds and no or poorly-documented tetanus vaccine history, incomplete tetanus immunization history, a history of HIV, or immunodeficiency. Pregnant individuals also should receive Tdap for wound management.

Catch-up immunization

Ages 7–18 years: Unvaccinated individuals should receive a series of 3 vaccines, including at least 1 Tdap dose. The preferred schedule is 1 dose of Tdap, followed by either Td or Tdap at least 4 weeks later, and another dose 6–12 months after that. Those with incomplete vaccination histories do not need to restart the series.

Ages ≥19 years: Similar to younger individuals, those who have never been vaccinated should receive a series of 3 vaccines, starting with Tdap.

Prevention of neonatal and obstetric tetanus

Pregnant individuals who completed their childhood immunization schedule but were last vaccinated over 10 years ago should receive a booster. If a previously unvaccinated patient receives at least 2 properly spaced doses of a tetanus toxoid-containing vaccine during pregnancy, including 1 Tdap, the risk for neonatal tetanus is significantly reduced.

CDC guidance on immunization

For catch-up immunization, if a child aged 7–9 years receives Tdap, an adolescent Tdap dose still should be administered at ages 11–12 years.

Inadvertent administration

DTaP is not recommended for individuals aged ≥7 years. If inadvertently administered, appropriate follow-up doses should be given based on the individual's vaccination status.

Off-label use of vaccine

Off-label indications remain unchanged, with new off-label uses for additional Td doses beyond the second dose administered ≥8 years after the initial Tdap.

Reporting adverse reactions

Adverse events following vaccination should be reported to the Vaccine Adverse Event Reporting System (VAERS) through online, fax, or mail submissions.

For comprehensive details, refer to the CDC guidelines.

For persons aged 7 years or older who never have been vaccinated against tetanus, diphtheria, or pertussis (ie, have never received any dose of DTP/DTaP/DT or Td), administer a series of 3-4 vaccinations containing tetanus and diphtheria toxoids. The preferred schedule is a single dose of Tdap, followed by a dose of Td at least 4 weeks after Tdap and another dose of Td 6-12 months later. However, Tdap can be given once as a substitute for Td in the 3-dose primary series.^[51]

Alternatively, in situations where the adult probably received vaccination against tetanus and diphtheria but cannot produce a record, vaccine providers may consider serologic testing for antibodies to tetanus and diphtheria toxin with the aim of avoiding unnecessary vaccination. If tetanus and diphtheria antitoxin levels are each higher than 0.1 IU/mL, previous vaccination with tetanus and diphtheria toxoid vaccine is presumed, and a single dose of Tdap is indicated.^[51]

Adults who received other incomplete vaccination series against tetanus and diphtheria should be vaccinated with Td to complete a 3-dose primary series of tetanus and diphtheria toxoid-containing vaccines. One dose of Tdap should be used in place of Td if the patient has never received a dose of Tdap.

Pregnancy is not a contraindication to the use of Tdap in the second and third trimester.^[51]

Secondary prevention of tetanus is accomplished after exposure through appropriate wound cleansing and debridement and the administration of tetanus toxoid (Td, Tdap, DT, DPT, or DTaP, as indicated) and TIG, when indicated. Pediatric formulations (DT and DTaP) include about the same amount of tetanus toxoid as adult Td does but contain 3-4 times as much diphtheria toxoid.

The following wounds should be considered prone to tetanus:

• Wounds that have been present for longer than 6 hours
• Deep (> 1 cm) wounds
• Grossly contaminated wounds
• Wounds that are exposed to saliva or feces, stellate, or ischemic or infected (including abscesses)
• Avulsions, punctures, or crush injuries

It is not necessary to wait the typical 10 years to get the adult Tdap dose after the last Td dose.^[51] An interval as short as 2 years is suggested to reduce the likelihood of increased reactogenicity, and even shorter intervals may be appropriate if the patient is at high risk for pertussis, has close contact with infants, or may not be able to receive another vaccination. Providers should know that shorter intervals are not contraindicated, that accumulating data reinforce safety of the vaccine, and that there are no concerns about immunogenicity with the decreased interval.

Patients with tetanus-prone wounds should receive Td or DPT IM if they are younger than 7 years and if it has been more than 5 years since their last dose of tetanus toxoid.^[51] Patients who previously have received fewer than 3 doses of tetanus toxoid and patients aged 60 years or older should receive TIG 250-500 units IM, always in the opposite extremity to the toxoid.

Adults without tetanus-prone wounds should be given Td or Tdap if they previously have received fewer than 3 doses of tetanus toxoid or if more than 10 years have passed since their last dose.46 Tdap is preferred to Td for adults vaccinated more than 5 years earlier who require tetanus toxoid as part of wound management and who have not previously received Tdap. Tdap is indicated only once; therefore, for adults previously vaccinated with Tdap (after age 7 years), Td should be used if a tetanus toxoid−containing vaccine is indicated for wound care.

It is important to review the immunization status of all patients who present to an emergency department for any care (regardless of chief complaint). Immunizations should be administered if a lapse of more than 10 years has occurred since the last tetanus booster. If a patient does not remember or cannot give a history of immunization, an immunochromatographic dipstick test may be appropriate and cost-effective for determining tetanus immunity in this setting. However, clinical judgement still should be employed when using these tests due to the risk for false positives for tetanus immunity, and further testing likely is needed before tetanus quick sticks are widely adopted.^[52]

The ACIP recommends vaccination at primary care visits for adolescents aged 11-12 years and for adults aged 50 years, review of vaccination histories, and updating of tetanus vaccination status. This is in addition to recommending booster doses of tetanus and diphtheria toxoid every 10 years.

Worldwide, neonatal tetanus may be eliminated by increasing immunizations in cisgender women of childbearing age and pregnant individuals, and by improving maternity care.^[12] Administration of tetanus toxoid twice during pregnancy (4-6 weeks apart, preferably in the last 2 trimesters) and again at least 4 weeks before delivery is recommended for previously unimmunized gravid patients. Antitetanus antibodies are passed to the fetus during pregnancy, and this passive immunity is effective for many months.

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Guidelines Summary

Prevention of tetanus is accomplished through vaccination with DTP or DTaP at ages 2 months, 4 months, 6 months, 12-18 months, and 4-6 years.

The following organizations have released guidelines on the use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines. Key diagnostic and management recommendations have been reviewed and integrated throughout the article.

• 2025 Recommended Childhood and Adolescent Immunization Schedule: United States, 2025: Policy Statement. Approved by Centers for Disease Control and Prevention (CDC), American Academy of Pediatrics (AAP), American Academy of Family Physicians, American College of Obstetricians and Gynecologists, American College of Nurse-Midwives, American Academy of Physician Associates, and National Association of Pediatric Nurse Practitioners.^[51]  

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Medication Summary

The goals of pharmacotherapy are to stop toxin production within the wound, to neutralize unbound toxin, and to control disease manifestations. Drugs used to treat muscle spasm, rigidity, and tetanic seizures include sedative-hypnotic agents, general anesthetics, centrally acting muscle relaxants, and neuromuscular blocking agents. Antibiotics are used to prevent multiplication of Clostridium tetani, thus halting production and release of toxins. Antitoxins are given to neutralize unbound toxin.

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Metronidazole (Flagyl)

• Dosing, Interactions, etc.

Clinical Context:  Metronidazole is active against various anaerobic bacteria and protozoa. It appears to be absorbed into cells, and intermediate-metabolized compounds that are formed bind DNA and inhibit protein synthesis, causing cell death. A 7-10 day course of treatment is recommended. Some consider it the drug of choice in tetanus because of its safety profile, efficient penetration into wounds and abscesses, and negligible central nervous system (CNS) excitation.

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Penicillin G (Pfizerpen)

• Dosing, Interactions, etc.

Clinical Context:  Penicillin G is a bactericidal antibiotic that binds to and inhibits penicillin-binding proteins, which are transpeptidases that cross-link peptidoglycans, the final step in bacterial cell wall synthesis. Inhibition of cell wall synthesis and autolytic enzyme activation are responsible for its bactericidal action on dividing bacteria.

A 7-10 day course of treatment is recommended. Large intravenous (IV) doses of penicillin may cause hemolytic anemia and neurotoxicity. Cardiac arrest has been reported in patients receiving massive doses of penicillin G potassium. Patients with renal failure are particularly at risk.

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Doxycycline (Vibramycin, Doryx, Doxy 100, Adoxa, Monodox)

• Dosing, Interactions, etc.

Clinical Context:  Doxycycline inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. A 10- to 14-day course of treatment is recommended.

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Erythromycin (E.E.S., EryPed, Erythrocin, Ery-Tab)

• Dosing, Interactions, etc.

Clinical Context:  Erythromycin is a bacteriostatic agent that inhibits protein synthesis by binding to the 50S subunit of bacterial ribosomes. It is not the drug of choice for tetanus but may be used when the drugs of choice cannot be administered for some reason.

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Clindamycin (Cleocin)

• Dosing, Interactions, etc.

Clinical Context:  Clindamycin is a bacteriostatic agent that binds to the 50S ribosomal subunit. It is not the drug of choice for tetanus and may be used only if the drugs of choice cannot be used.

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Tetracycline

• Dosing, Interactions, etc.

Clinical Context:  Tetracycline is a bacteriostatic agent that inhibits protein synthesis. It is not the drug of choice for tetanus and may be used only if the drugs of choice cannot be used.

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Vancomycin

• Dosing, Interactions, etc.

Clinical Context:  Vancomycin is a bactericidal agent that inhibits cell wall and RNA synthesis. It is not the drug of choice for tetanus and may be used only if the drugs of choice cannot be used.

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Class Summary

These agents are used to eradicate clostridial organisms in the wound, which may produce tetanus toxin. They are administered to patients with clinical tetanus; however, their efficacy is questioned. Pencillin G was long considered the primary antibiotic of choice. However, metronidazole is now considered first line treatement with Penicillin G an acceptable alternative therapy.^[53]

Although tetracyclines are an alternative in patients who have a history of serious allergic reactions to penicillin or metronidazole (eg, urticaria, anaphylaxis), strong consideration should be given to desensitizing the patient to penicillin before resorting to alternative agents. Large doses of antibiotic are recommended to favor diffusion into the devitalized tissue.

The CDC does not recommend use of antibiotics for prophylaxis. However, they should be used in the case of apparent wound infection.^[1]

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Diazepam (Valium, Diastat, Diazepam Intensol)

• Dosing, Interactions, etc.

Clinical Context:  Diazepam modulates the postsynaptic effects of GABA-A transmission, thereby increasing presynaptic inhibition. It appears to act on part of the limbic system, the thalamus, and hypothalamus to induce a calming effect. It is also an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders. Diazepam rapidly distributes to other body fat stores. To avoid adverse effects, individualize dosage and increase it cautiously.

Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentration drops to 20% of Cmax.

Individualize dosage and increase cautiously to avoid adverse effects.

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Midazolam (Versed)

• Dosing, Interactions, etc.

Clinical Context:  Midazolam is a shorter-acting benzodiazepine sedative-hypnotic that is useful in patients requiring acute or short-term sedation. It also has amnestic and antiepileptic effects.

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Lorazepam (Ativan)

• Dosing, Interactions, etc.

Clinical Context:  Lorazepam is a sedative hypnotic with a short onset of effects and a relatively long half-life. By increasing the action of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the central nervous system, including the limbic and reticular formation. The drug is an excellent choice when the patient needs to be sedated for longer than 24 hours.

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Phenobarbital

• Dosing, Interactions, etc.

Clinical Context:  The drug dosage must be small enough to ensure that respirations are not depressed. If the patient is already on a ventilator, higher dosages may provide the desired sedation.

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Magnesium sulfate (MgSO4)

• Dosing, Interactions, etc.

Clinical Context:  Magnesium sulfate is generally recommended to help control spasms and autonomic dysfunction. Notably, it has no effect on overall mortality, but can decrease length of hospital stay and rate of ventilator usage.

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Class Summary

Sedative-hypnotic agents are the mainstays of tetanus treatment. Benzodiazepines are the most effective primary agents for muscle spasm prevention and work by enhancing gamma-aminobutyric acid (GABA) inhibition. Diazepam is the most frequently studied and used drug. Lorazepam is an effective alternative. Phenobarbital is another anticonvulsant that may be used to prolong the effects of diazepam. Other agents used for spasm control include magnesium sulfate, baclofen, dantrolene, short-acting barbiturates, and chlorpromazine.

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Baclofen (Lioresal, Gablofen)

• Dosing, Interactions, etc.

Clinical Context:  Baclofen, a central muscle relaxant, is a presynaptic GABA-B receptor agonist that may induce hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at spinal level. It lessens flexor spasticity and hyperactive stretch reflexes of upper motor neuron origin.

Baclofen is well absorbed, with an average oral bioavailability of 60% and a mean elimination half-life of 12 hours. Steady state is reached within 5 days with multiple dose administration. Metabolism occurs in the liver (through P450-dependent glucuronidation and hydroxylation); 6 major and a few minor metabolites are produced. Elimination is through renal excretion.

For intrathecal (IT) administration, a pump is implanted subcutaneously (SC), and a catheter is implanted in the subarachnoid space of the spinal canal (where the medication is administered). Less medication is needed, and systemic effects are decreased. This agent is reported to be effective in about 20% of patients; it appears to be of dramatic benefit in as many as 30% of children with dystonia, though the benefit not always sustained.

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Dantrolene (Dantrium, Revonto)

• Dosing, Interactions, etc.

Clinical Context:  Dantrolene stimulates muscle relaxation by modulating skeletal muscle contractions at a site beyond the myoneural junction and by acting directly on the muscle. It may reduce painful cramping and detrimental muscle tightening. It is not approved by the US Food and Drug Administration (FDA) for use in tetanus but has been described in a small number of case reports.

Dantrolene acts peripherally at muscle fiber rather than at the neural level; it reduces muscle action potential–induced release of calcium and also affects intrafusal and extrafusal fibers and spindle sensitivity. It has no action on smooth or cardiac muscle tissue. Dantrolene induces release of calcium ions into the sarcoplasmic reticulum, subsequently decreasing the force of excitation coupling.

Dantrolene is preferred for the cerebral form of spasticity; it is less likely to cause lethargy or cognitive changes, as baclofen and diazepam do. It can be administered either orally or IV. The IV form is much more expensive and should be reserved for patients unable to take oral medications. Most patients respond to dosages of 400 mg/day or less. The drug is eliminated in urine and bile.

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Class Summary

Skeletal muscle relaxants can inhibit both monosynaptic and polysynaptic reflexes at spinal level, possibly by hyperpolarization of afferent terminals. Benzodiazepines are used to control muscle spasms and to provide sedation. Dantrolene and baclofen may also be considered for severe spasticity and may assist with shortening duration of artificial ventilation. The use of propofol has been proposed.

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Propofol (Diprivan)

• Dosing, Interactions, etc.

Clinical Context:  Propofol is a phenolic compound that elicits a sedative-hypnotic effect. It is used for induction and maintenance of anesthesia or sedation. It has also been shown to have anticonvulsant properties.

• References

Class Summary

These agents stabilize the neuronal membrane so the neuron is less permeable to ions. This prevents the initiation and transmission of nerve impulses, thereby producing the local anesthetic effects.

• References

Tetanus immune globulin (Hypertet S/D)

• Dosing, Interactions, etc.

Clinical Context:  TIG is used to prevent tetanus and to treat patients with circulating tetanus toxin. It provides passive immunity. TIG should be used to treat all patients with active tetanus, in combination with other supportive and therapeutic treatments. Administration should begin as soon as the clinical diagnosis of tetanus is made.

TIG should also be given in conjunction with prophylactic Tdap vaccination for patients with dirty wounds and poorly-document or no history of tetanus vaccination. 

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Class Summary

Antitoxins are used to neutralize any toxin that has not reached the CNS. They are used for passive immunization of any person with a wound that might be contaminated with tetanus spores.

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Vecuronium

• Dosing, Interactions, etc.

Clinical Context:  Vecuronium is a prototypical nondepolarizing neuromuscular blocking agent that reliably results in muscular paralysis. For maintenance of paralysis, a continuous infusion may be used. Infants are more sensitive to neuromuscular blockade activity, and though the same dose is used, recovery is prolonged by 50%. This drug is not recommended for use in neonates.

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Class Summary

Neuromuscular blocking agents inhibit the transmission of nerve impulses at neuromuscular junctions of skeletal muscles or autonomic ganglia.

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Diphtheria & tetanus toxoids/acellular pertussis vaccine (Daptacel, Infanrix)

• Dosing, Interactions, etc.

Clinical Context:  DTaP may be administered into the deltoid or midlateral thigh muscles in children and adults. In infants, the preferred site of administration is the midlateral thigh muscles.

This vaccine promotes active immunity to diphtheria, tetanus, and pertussis by inducing the production of specific neutralizing antibodies and antitoxins.

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Tetanus & reduced diphtheria toxoids/acellular pertussis vaccine (Adacel, Boostrix, Tdap)

• Dosing, Interactions, etc.

Clinical Context:  Promotes active immunity to diphtheria, tetanus, and pertussis by inducing the production of specific neutralizing antibodies and antitoxins. It is indicated for active booster immunization for persons aged 10 or older (Adacel approved for ages 10-64 y, Boostrix approved for ages 10 y or older). It is the preferred vaccine for adolescents scheduled for a booster vaccination.

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Class Summary

Active immunization increases resistance to infection. Vaccines consist of microorganisms or cellular components that act as antigens. Administration of the vaccine stimulates the production of antibodies with specific protective properties. Administer tetanus toxoid vaccine for wound prophylaxis if the vaccine history is unknown or if fewer than 3 tetanus toxoid immunizations have been administered.

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