AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Tetanus is an infectious disorder characterized by increased muscle tone and spasms caused by the release of the neurotoxin tetanospasmin by Clostridium tetani following inoculation into a human host. Tetanus occurs in several clinical forms, including generalized, cephalic, localized, and neonatal disease.

Pathophysiology

Most cases of tetanus are caused by direct contamination of wounds with clostridial spores. Wounds with low oxidation-reduction potential, such as those with dead or devitalized tissue, a foreign body, or active infection, are ideal for germination of the spores and release of toxin. Infection by C tetani results in a benign appearance at the portal of entry because of its inability to evoke an inflammatory reaction (unless co-infection with other organisms develops).

Tetanospasmin, a zinc metalloprotease, is released in the wound and binds to the peripheral motor neuron terminal, enters the axon, and, via retrograde intraneuronal transport, reaches the nerve cell body in the brainstem and spinal cord. The toxin migrates across the synapse to presynaptic terminals where it blocks the release of the inhibitory neurotransmitters glycine and gamma-aminobutyric acid (GABA) by cleaving proteins crucial for the proper functioning of the synaptic vesicle release apparatus. One of these important proteins is synaptobrevin. This diminished inhibition results in an increase in the resting firing rate of the motor neuron, which is responsible for the observed muscle rigidity.

The lessened activity of reflexes limits the polysynaptic spread of impulses (a glycinergic activity). Agonists and antagonists may be recruited rather than inhibited, with consequent production of spasms. Loss of inhibition may also affect preganglionic sympathetic neurons in the lateral gray matter of the spinal cord and produce sympathetic hyperactivity and high levels of circulating catecholamines. Finally, tetanospasmin can block neurotransmitter release at the neuromuscular junction, causing weakness and paralysis.

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.

Frequency

United States

Neonatal tetanus is rare. Tetanus affects nonimmunized persons, partially immunized persons, or fully immunized individuals who do not maintain adequate immunity with periodic booster doses. The risk for development of tetanus and for the most severe form of the disease is highest in the elderly population. Most cases follow an acute injury, such as a puncture wound, a laceration, or an abrasion.

Tetanus can be acquired outdoors as well as indoors. The injury is usually trivial, and, often, no initial medical treatment is sought. Tetanus can also develop as a complication of some chronic conditions, such as decubitus ulcers, abscesses, and gangrene. Finally, it may complicate burns, frostbite, middle ear infections, surgery, abortion, childbirth, and intravenous or subcutaneous drug use. Fewer than 50 cases of tetanus per year have been recorded since 1995. The infection has not been transmitted from person to person.

International

C tetani is found worldwide in soil, on inanimate objects, in animal feces, and, occasionally, in human feces. The disease 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.¹

Mortality/Morbidity

A rating scale for the severity and the prognosis of tetanus is described below.²

• Score one point for each of the following:
• • Incubation period less than 7 days
  • Period of onset less than 48 hours
  • Acquired from burns, surgical wounds, compound fractures, septic abortion, umbilical stump, or intramuscular injection
  • Narcotic addiction
  • Generalized tetanus
  • Temperature greater than 104°F (40°C)
  • Tachycardia greater than 120 beats per minute (>150 beats per minute in neonates)
• Total score indicates the severity and the prognosis as follows:
• • Score of 0-1 indicates mild severity with less than a 10% mortality rate.
  • Score of 2-3 indicates moderate severity with a 10-20% mortality rate.
  • Score of 4 indicates severe tetanus with a 20-40% mortality rate.
  • Score of 5-6 indicates very severe tetanus with greater than a 50% mortality rate.
  • Cephalic tetanus is always severe or very severe.
  • Neonatal tetanus is always very severe.

Race

No particular racial predilection has been reported.

Sex

No sex predilection has been reported, except to the extent that males may have more soil exposure in some cultures.

Age

Neonatal tetanus is most common in countries without comprehensive vaccination programs. Otherwise, most severe disease develops in elderly people. Age predilection is mostly governed by soil exposure patterns.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

The etiologic agent, C tetani, is an anaerobic, motile, gram-positive rod that forms an oval, colorless, terminal spore and assumes a shape that resembles a tennis racket or a drumstick. The organism is found worldwide. The spores may survive for years in some environments and are resistant to disinfectants and to boiling for 20 minutes. Vegetative cells are easily inactivated and are susceptible to several antibiotics. Patients sometimes remember an injury, but, many times, the injury goes unnoticed.

• Generalized tetanus: Generalized tetanus is the most commonly found form of tetanus in the United States, accounting for 85-90% of cases. The extent of the trauma varies from trivial injury to contaminated crush injury. The incubation period is 7-21 days, largely depending on the distance of the injury site from the CNS. 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 they 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 widely varies in severity. This is an unusual form of tetanus and the prognosis for survival is excellent.
• Cephalic tetanus: Cephalic tetanus generally follows head injury or develops with infection of the middle ear. Symptoms consist of isolated or combined dysfunction of the cranial motor nerves (most frequently the seventh cranial nerve). It may remain localized or progress to generalized tetanus. This is an unusual form of tetanus with an incubation period of 1-2 days. The prognosis for survival is usually poor.
• Tetanus neonatorum: This is generalized tetanus that results from infection of a neonate. It primarily occurs in underdeveloped countries and accounts for up to one half of all neonatal deaths. 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 3-10 days, which is why it is sometimes referred to as the disease of the seventh day. The newborn usually exhibits irritability, poor feeding, rigidity, facial grimacing, and severe spasms with touch. The mortality rate exceeds 70%.

Physical

• Generalized tetanus: Sustained trismus may result in the characteristic sardonic smile (risus sardonicus) and persistent spasm of the back musculature may cause opisthotonus. Waves of opisthotonus 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 autonomic nervous system may result in severe arrhythmias, oscillation of the blood pressure, profound diaphoresis, hyperthermia, rhabdomyolysis, laryngeal spasm, and urinary retention. In most cases, the patient remains lucid.
• Localized tetanus: In mild cases, patients may have weakness of the involved extremity, presumably due to partial immunity. In more severe cases, intense painful spasms occur and usually progress to generalized tetanus.
• Cephalic tetanus: Cranial nerve findings and rapid progression are typical. This form may remain localized or progress to generalized tetanus.
• Tetanus neonatorum: Physical examination findings are similar to generalized tetanus findings.

Causes

Causes of tetanus include underimmunization and the use of contaminated materials in newborn care.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Strychnine poisoning
Dystonic drug reactions (eg, phenothiazines, metoclopramide)
Hypocalcemic tetany
Encephalitis
Acute intra-abdominal process (due to rigid abdomen)

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• The diagnosis of tetanus is based entirely on clinical findings. Tetanus is unlikely if a reliable history indicates the completion of a primary vaccination series and the receipt of required booster doses.
• Wounds should be cultured in suspected cases. However, C tetani can be cultured from wounds of patients without tetanus and frequently cannot be cultured from wounds of patients with tetanus.
• The leukocyte count may be high.
• Cerebrospinal fluid examination yields normal results.
• Serum antitoxin levels of 0.01 or higher are considered protective and make tetanus unlikely, although rarely cases have been reported despite the presence of protective antitoxin levels.
• Serum muscle enzyme levels (eg, creatine kinase, aldolase) may be elevated.

Other Tests

• Electromyography may show continuous discharge of motor subunits and shortening or absence of the silent interval normally observed after an action potential.
• Nonspecific changes may be evident on electrocardiography.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical Care

The goals of treatment are 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, and managing complications.

• Initial supportive therapy: The patient should be placed in a quiet room in an ICU. If ventilation is compromised, the patient should be sedated, intubated, and provided with a soft nasal feeding tube. A tracheostomy may be needed.
• Wound debridement and care: The possibility of developing tetanus directly correlates with the characteristics of the wound. 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 grossly contaminated or caused by blunt trauma or bites. Wounds should be explored, carefully cleansed, and properly debrided.
• Stopping toxin production: Antimicrobials are used to decrease the number of vegetative forms (source of toxin) of C tetani in the wound. The current antimicrobial drug of choice is metronidazole, with penicillin as an alternative treatment. A higher survival rate was obtained with metronidazole than with penicillin in one nonrandomized trial. Less CNS excitation is seen with metronidazole than with penicillin. Other antimicrobials that have been used include clindamycin, erythromycin, tetracycline, and vancomycin.
• Neutralizing unbound toxin
  • Human tetanus immunoglobulin (TIG) is recommended for treatment. A single total dose of 3000-6000 U is recommended for children and adults. The optimal dose has not yet been established, but doses as low as 500 U have been effective in infants with tetanus neonatorum.
  • Available preparations must be intramuscularly administered at the time of diagnosis to prevent further circulating toxin from reaching the CNS. Some authorities recommend infiltration of part of the dose locally around the wound, although the efficacy of this approach has not been proven.
  • The TIG formulation available in the United States is not licensed or appropriate for intravenous or intrathecal use. In countries in which TIG is not available, equine tetanus antitoxin may be available.
  • Tetanus antitoxin is administered as a single dose of 50,000-100,000 U after appropriate testing for sensitivity and desensitization, if necessary. Part of this dose (20,000 U) should be intravenously administered.
  • Guide to Tetanus Prophylaxis in Wound Management

  History of Absorbed Tetanus Toxoid	Clean Minor Wounds		All Other Wounds
  	Tdap*	TIG	Tdap	TIG
  Unknown or <3 doses	Yes	No	Yes	Yes
  3 or more doses	No	No	No	No

  *Tdap is Tetanus-diphtheria-acellular pertussis

• Controlling disease manifestations: A benzodiazepine should be used to produce sedation, decrease rigidity, and control spasms (midazolam administered intravenously at 5-15 mg/h is suitable). If the spasms are not controlled with benzodiazepines, long-term neuromuscular blockade is required.
• Managing complications: Specific therapy for autonomic system complications and control of spasms should be initiated. Sympathetic hyperactivity is treated with combined alpha and beta blockade or morphine. Epidural blockade with local anesthetics may be needed. 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.

Consultations

Consultations with infectious diseases specialists and other specialists may be appropriate as the clinical situation dictates.

Diet

Patients should not be given any food by mouth because of the risk of aspiration. Nutrition should be intravenously supported. Consultation with a nutritionist is helpful.

Activity

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

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The goals of pharmacotherapy are to stop toxin production within the wound, to neutralize unbound toxin, and to control disease manifestations. Magnesium infusion may help relieve muscle spasm and diminish sedation requirements.³

Drug Category: Antimicrobial agents

These agents are used to eradicate clostridia in the wound, which may cause toxin production.

Drug Name	Penicillin G (Pfizerpen)
Description	Bactericidal antibiotic. Binds to and inhibits penicillin-binding proteins, which are transpeptidases that cross-link peptidoglycans, the final step in bacterial cell wall synthesis. Inhibits cell wall synthesis and autolytic enzyme activation are responsible for the bactericidal action on dividing bacteria.
Adult Dose	4 million U IV q4h; not to exceed 24 million U/d
Pediatric Dose	100,000 U/kg/d IV/IM divided q4h; not to exceed 24 million U/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin; synergistic with aminoglycosides; may decrease methotrexate elimination; may decrease PO contraceptive effect
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution with renal impairment (decrease dose); caution with preexisting seizure disorder

Drug Name	Erythromycin (E.E.S., E-Mycin, Eryc, EryPed, Erythrocin)
Description	Bacteriostatic agent that inhibits protein synthesis by binding to the 50S subunit of bacterial ribosomes. Not the DOC for tetanus but may be used in case the DOCs for tetanus cannot be administered for some reason.
Adult Dose	15-50 mg/kg/d IV divided q6h; not to exceed 4 g/d
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; hepatic impairment; coadministration with astemizole, terfenadine, or cisapride
Interactions	CYP isoenzymes 1A2 and 3A3/4 inhibitor; decreases clearance of astemizole, terfenadine, alfentanil, carbamazepine, cisapride, cyclosporine, protease inhibitors, lovastatin, repaglinide, simvastatin, midazolam, phenytoin, theophylline, and triazolam; increases warfarin effect
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (administer pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug Name	Clindamycin (Cleocin)
Description	Bacteriostatic agent that binds to 50S ribosomal subunit and acts as a bacteriostatic agent. Not the DOC for tetanus. May be used only if other DOCs cannot be used.
Adult Dose	300-900 mg IV q6-12h; not to exceed 4800 mg/d
Pediatric Dose	Neonates <7 days: 10-15 mg/kg/d IV divided q8-12h Neonates >7 days: 10-20 mg/kg/d IV divided q6-12h Infants and children: 25-40 mg/kg/d IV divided q6-8h; not to exceed 4800 mg/d
Contraindications	Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of Clostridium difficile

Drug Name	Tetracycline (Sumycin)
Description	Bacteriostatic agent that inhibits protein synthesis. Not the DOC for tetanus. May be used only if other DOCs cannot be used.
Adult Dose	1-2 g/d PO divided bid
Pediatric Dose	<8 years: Contraindicated >8 years: 25-50 mg/kg/d PO divided q6h; not to exceed 3 g/d
Contraindications	Documented hypersensitivity; severe hepatic dysfunction; age <8 y
Interactions	Bioavailability decreases with antacids or vitamins containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy; can increase hypoprothrombinemic effects of anticoagulants; coadministration with isotretinoin increases risk of pseudotumor cerebri; increases atovaquone serum concentrations; quinapril decreases bioavailability, presumably because of high magnesium content of quinapril
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Vancomycin (Vancocin)
Description	Bacteriocidal agent that inhibits cell wall and RNA synthesis. Not the DOC for tetanus. May be used only if the DOCs cannot be used.
Adult Dose	1 g IV q12h initially; adjust dose according to renal function and pharmacokinetic parameters
Pediatric Dose	Neonates <7 days and <1200 grams: 15 mg/kg IV q24h Neonates <7 days and 1200-2000 grams: 10-15 mg/kg IV q12-18h Neonates <7 days and >2000 grams: 10-15 mg/kg IV q8-12h Neonates >7 days and <1200 grams: 15 mg/kg IV q24h Neonates >7 days and 1200-2000 grams: 10-15 mg/kg IV q8-12h Neonates >7 days and >2000 grams: 15-20 mg/kg IV q8h Infants and children: 10 mg/kg IV q6h; adjust dose according to renal function and pharmacokinetic parameters
Contraindications	Documented hypersensitivity
Interactions	Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; when taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution with impaired liver function, renal function (decrease dose), hearing loss, neutropenia, or age >60 y; red man syndrome is caused by too rapid IV infusion (dose administered over a few min) but rarely happens when dose is administered IV over 2 h or as PO or IP administration; red man syndrome is not an allergic reaction

Drug Category: Immunoglobulins

These agents are used for passive immunization of any person with a wound that might be contaminated with tetanus spores.

Drug Category: Vaccines

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 vaccine history is unknown or fewer than 3 tetanus toxoid immunizations have been administered.

Drug Name	Tdap (Adacel, Boostrix)
Description	Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine. Promotes active immunity to diphtheria, tetanus, and pertussis by inducing production of specific neutralizing antibodies and antitoxins. Indicated for active booster immunization for tetanus, diphtheria, and pertussis prevention for persons aged 10-64 y (Adacel approved for ages 11-64 y, Boostrix approved for ages 10-18 y). Preferred vaccine for adolescents scheduled for booster.
Adult Dose	One-time alternative to Td in adults when pertussis component is also indicated: 0.5 mL IM once as a single dose into deltoid muscle; at least 5 y should elapse since last dose vaccine containing tetanus, diphtheria, and/or pertussis; booster with Td recommended q10y >65 years: Not indicated
Pediatric Dose	<10 years: Not indicated 10-18 years: Administer as in adults; preferred vaccine for adolescents scheduled for booster
Contraindications	Documented hypersensitivity; encephalopathy within 7 d following pertussis-containing vaccine; progressive neurologic disorder; uncontrolled epilepsy; progressive encephalopathy
Interactions	Patients receiving immunosuppressants, including corticosteroids or radiation therapy, may remain susceptible despite immunization because of a poor immune response
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Routine immunization of symptomatic and asymptomatic persons infected with HIV is recommended; may cause transient redness, swelling, or pain at injection site; infrequently causes fever; administer only if benefit outweighs risk to individuals with bleeding disorders (eg, hemophilia, thrombocytopenia) or in patients receiving anticoagulant therapy; caution upon fever, shock, persistent crying, Guillain-Barré syndrome, or seizures following previous DTP or DTaP vaccine (consider administering Td instead)

Drug Category: Skeletal Muscle Relaxant

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.

Drug Name	Baclofen (Lioresal)
Description	Muscle relaxant (central), presynaptic GABA-B receptor agonist that may induce hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at spinal level. Lessens flexor spasticity and hyperactive stretch reflexes of upper motor neuron origin. Eliminated through renal excretion. Effective in about 20% of patients. Appears to be of dramatic benefit in as many as 30% of children with dystonia, although benefit not always sustained. Well absorbed, with average PO bioavailability of 60% and mean elimination half-life of 12 h; steady state reached within 5 d with multiple dose administration; metabolism occurs in liver (P 450-dependent glucuronidation and hydroxylation); 6 major and a few minor metabolites produced. For intrathecal (IT) administration, a pump is implanted SC and a catheter implanted in subarachnoid space of spinal canal (where medication is administered). Less medication needed and systemic effects decreased. Half-life approximately 5 h.
Adult Dose	Case reports of IT administration via single bolus or by continuous infusion over 24 h have shown effective for severe tetanus <55 years: 1000 mcg IT >55 years: 800 mcg IT
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Opiate analgesics, benzodiazepines, alcohol, tricyclic antidepressants, guanabenz, MAOIs, clindamycin, and hypertensive agents may increase baclofen effects
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution in patients with history of autonomic dysreflexia and when spasticity is utilized to obtain increased function; autonomic dysreflexia can result from withdrawal of this medication; respiratory depression may occur with IT dosage

Drug Name	Dantrolene (Dantrium)
Description	Acts peripherally at muscle fiber rather than at neural level; reduces muscle action potential–induced release of calcium and also affects intrafusal and extrafusal fibers and spindle sensitivity. Has no action on smooth or cardiac muscle tissue. Induces release of Ca++ into sarcoplasmic reticulum, subsequently decreasing the force of excitation coupling. Only drug that intervenes at a muscular level. Preferred for the cerebral form of spasticity. Less likely to cause lethargy or cognitive changes like baclofen or diazepam. May reduce painful cramping and detrimental muscle tightening. Can be administered PO/IV. IV form is much more expensive and should be reserved for patients unable to take PO medications. Most patients respond to 400 mg/d or less. Eliminated in the urine and bile.
Adult Dose	Begin with 25 mg PO qd; increase to 25 mg bid/qid, then by 25 mg increments to as high as 100 mg, bid/qid prn
Pediatric Dose	Start with 0.5 mg/kg PO bid, increase to 0.5 mg/kg, bid/qid, then by increments of 0.5 mg/kg, to 3 mg/kg bid/qid if necessary; not to exceed 100 mg qid
Contraindications	Documented hypersensitivity; active hepatic disease (hepatitis and cirrhosis)
Interactions	Toxicity may increase with coadministration of clofibrate and warfarin; coadministration with estrogen may increase hepatotoxicity in women older than 35 y
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	May cause hepatotoxicity (use only for recommended indications); caution in impaired pulmonary function and severe cardiac insufficiency; may cause photosensitivity with exposure to sunlight

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• Patients typically require intensive care.

Transfer

• The patient should be transferred if the necessary services are not locally available.

Deterrence/Prevention

• Tetanus is completely preventable by active immunization.
• Immunizations for children include tetanus toxoid, usually in the form of diphtheria, tetanus, and acellular pertussis vaccine. The immunizations are recommended at age 2 months, 4 months, 6 months, 12-15 months, and 4-6 years. A tetanus, diphtheria, and pertussis (Tdap) booster dose is administered at age 11-12 years and thereafter every 10 years.
• For the primary immunization of adults, tetanus toxoid is administered as 2 doses 4-6 weeks apart, with a third dose 6-12 months later. Booster doses are administered every 10 years or at the time of major injury if it occurs more than 5 years after a dose.
• Passive immunization should be used in nonimmunized individuals and those whose immunization status is uncertain whenever a wound is contaminated or likely to have devitalized tissue. TIG is used for passive immunization.

Complications

• Airway obstruction is common.
• Urinary retention and constipation may develop because of sphincter spasm.
• Respiratory failure and cardiac failure are late life-threatening events.⁴
• Fractures may result from sustained spasms.
• Seizures can occur.
• Pulmonary emboli may develop.
• Bacterial superinfections are possible complications.
• Dehydration can develop.

Prognosis

High mortality rates are associated with the following:

• Short incubation period
• Early onset of convulsions
• Delay in treatment
• Contaminated lesions of the head and the face
• Neonatal tetanus

Patient Education

• Stress the importance of childhood immunizations and boosters.
• Train midwives and birth attendants in developing and underdeveloped countries about aseptic birthing procedures.
• Teach the basics of wound care and first aid. Early recognition of symptoms and signs of localized tetanus and timely access to medical care are essential.
• For excellent patient education resources, visit eMedicine's Infections Center, Public Health Center, and Children's Health Center. Also, see eMedicine's patient education articles Tetanus; Immunization Schedule, Adults; and Immunization Schedule, Children.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Failure to consider the diagnosis in the appropriate context
• Failure to provide adequate supportive care

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Sonali Ray, MD, to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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6. Attygalle D, Rodrigo N. New trends in the management of tetanus. Expert Rev Anti Infect Ther. Feb 2004;2(1):73-84. [Medline].
7. Beltran A, Go E, Haq M, Clarke HB, Zaman M, Recco RA. A case of clinical tetanus in a patient with protective antitetanus antibody level. South Med J. Jan 2007;100(1):83. [Medline].
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Article Last Updated: Feb 1, 2008