TETANUS

PHARMACOTHERAPY I- INFECTIOUS DISEASE

TETANUS
OUTLINE
• Definition
• Pathophysiology
• Clinical manifestation
• Therapeutic management
TETANUS
• Acute, potentially fatal disease that is characterized by generalized
increased of rigidity and convulsive spasms of skeletal muscles
• Toxin-mediated disease caused by Clostridium tetani
• Can affect any age group and case-fatality rates are high (10-80%)
• No natural immunity against it
• Outbreaks of the disease are usually related to injuries associate with
natural disasters such as earthquakes, floods, tsunamis
• Tetanus may follow elective surgery, burns, deep puncture wounds, crush
wounds, otitis media, dental infection, animal bites, circumcision, abortion,
and pregnancy
TETANUS: epidemiology

Tetanus cases reported worldwide (1990-2004). Ranging from strongly

prevalent (in dark red) to very few cases (in light yellow), no data (grey)
TETANUS: epidemiology

Tetanus cases reported in few hospitals in Indonesia (2003-2007)

PHARMACOTHERAPY I- INFECTIOUS DISEASE

TETANUS
OUTLINE
• Definition

• Pathophysiology
• Clinical manifestation
• Therapeutic management
TETANUS: etiology
Clostridium tetani
• Rod-shaped, gram-positive, anaerobic, and endospore-forming bacteria Clostridium
tetani
• C. tetani spores (the dormant form of the organism) are a normal
inhabitant of soil and are found in animal and human feces and are
ubiquitous in the environment, especially where contamination by excreta
is common
• The spores enter the body through breaks in the skin, and germinate
under low-oxygen conditions
• Under anaerobic condition, C. tetani secretes potent exotoxins:
tetanospasmin & tetanolysin
tetanus is caused by
bacterium found in soil
TETANUS: pathophysiology
Clostridium tetani’s exotoxin

tetanospasmin tetanolysin

blocks the release of inhibitory locally damaging other viable tissue

neurotransmitter, leads to the surrounding the infection site and
clinical syndrome of tetanus optimizing the conditions for bacterial
multiplication
TETANUS: pathophysiology
Tetanopasmin mode of action
Tetanospasmin binds to inhibitory interneurons of the
spinal cord and blocks their release of inhibitory
neurotransmitter.
The toxin, by blocking the release of inhibitors, keeps the
involved muscles in a state of contraction due to
acetylcholine stimuli and leads to spastic paralysis, a
condition where opposing flexor and extensor muscles
simultaneously contract.
PHARMACOTHERAPY I- INFECTIOUS DISEASE

TETANUS
OUTLINE
• Definition
• Pathophysiology

• Clinical manifestation
• Therapeutic management
TETANUS: clinical features & diagnosis
• Incubation period varies from 3 to 21 days
• The shorter the incubation period, the higher incidence of death
• In neonatal tetanus, symptoms usually appear from 4 to 14 days after
birth
• There are no laboratory findings characteristic of tetanus. The diagnosis
is entirely clinical and does not depend upon bacteriologic confirmation
• presence of site of infection (wound); contamination of wounds with
soil, manure, or rusty metal; complication of burns, ulcers, gangrene,
necrotic snakebites, middle ear infections, septic abortions,
childbirth, surgery
• clinical symptoms
• distinguish from differential diagnosis >> spatula test
TETANUS: clinical features & diagnosis
TETANUS: clinical manifestation
Tetanus can manifest in one of four clinical forms:
• Generalized tetanus (lockjaw) is a neurologic disease manifesting as
trismus, followed by stiffness of the neck, difficulty in swallowing,
and rigidity of abdominal muscles. The disease usually presents
with a descending pattern
• Local tetanus is an uncommon form of the disease and manifests as
local muscle spasms in areas contiguous to a wound
• Cephalic tetanus is a rare form of the disease, occasionally
occurring with otitis media, or associated with infected wounds on
the head and neck causing dysfunction of cranial nerves
• Neonatal tetanus is a form of generalized tetanus occurring in
newborn infants lacking protective passive immunity because their
mothers are not immune and due to non-sterile umbilical cord-care
practices
TETANUS: clinical manifestation
TETANUS: clinical manifestation
TETANUS: severity grading (Ablett classification)
PHARMACOTHERAPY I- INFECTIOUS DISEASE

TETANUS
OUTLINE
• Definition
• Pathophysiology
• Clinical manifestation

• Therapeutic management
TETANUS: treatment goals
GOALs of treatment: wound management
1) Halting production of toxin within the wound
antibiotic therapy

2) Neutralization of unbound toxin passive immunization

3) Control of muscle spasms muscle relaxants

4) Management of autonomic instability anaesthesia

5) Supportive therapy airway, hydration, nutrition
6) Management of complications
7) Prevention active immunization
TETANUS: management
1. Halting production of toxin within the wound
>> wound management
• Potential tetanus-incubating wounds should undergo
debridement (important to eradicate spores and change
conditions for germination, thereby preventing further wound
debridement
elaboration and absorption of the neurotoxin)
• Abscesses should be incised and drained
TETANUS: management
1. Halting production of toxin within the wound
>> antibiotic therapy
• First-line
metronidazole
metronidazole 500 mg every six hours oral or
intravenously;
• Alternatives
Penicillin G (100,000–200,000 IU/kg/day intravenously,
given in 2–4 divided doses), tetracyclines, macrolides,
clindamycin, cephalosporins and chloramphenicol
TETANUS: management
2. Neutralization of unbound toxin

PASSIVE IMMUNIZATION
• First-line
Tetanus Immunoglobulin (TIG)
• Alternatives
Equine Tetanus Antitoxin (ATS)

3. Prevention

ACTIVE IMMUNIZATION
• Tetanus Toxoid
TETANUS: management
4. Control of muscle spasms

• First-line
Benzodiazepines >> diazepam, lorazepam, midazolam
• Alternatives
Magnesium sulphate (alone or in combination with
benzodiazepine), baclofen, dantrolene, barbiturates
(preferably short-acting, potential drug interactions with
metronidazole), chlorpromazine
5. Management of autonomic dysfunction

• Magnesium sulphate or morphine

TETANUS: management
6. Supportive therapy

• Airway / respiratory control

drugs used to control spasm and provide sedation can
result in respiratory depression >> patients must be
carefully monitored, early tracheostomy is preferred
• Adequate fluids and nutrition
tetanus spasms result in high metabolic demands and a
catabolic state >> nutritional support will enhance
chances of survival
TETANUS: prophylaxis in wound management (CDC & WHO)
WOUND ASSESSMENT

CLEAN, MINOR WOUND ALL OTHER WOUNDS

history of primary tetanus vaccine history of primary tetanus vaccine

NO/ YES NO/ YES

UNKNOWN UNKNOWN
the most recent
administer vaccine the most recent dose is administer dose is within the
within the past 10 years vaccine + TIG past 5 years

NO YES NO YES

administer vaccine administer vaccine

vaccine not needed vaccine not needed
 TETANUS: prophylaxis in wound management (CDC & WHO)
• Other wounds: such as (but not limited to) wounds
contaminated with dirt, feces, soil, saliva; puncture
wounds, avulsions, and wounds resulting from
missiles, crushing, burns, and frostbite
• TIG is human tetanus immune globulin, equine
tetanus antitoxin should be used when TIG is not
available
• A primary series consists of a minimum of 3 doses
of tetanus and diphtheria containing vaccine
(DTaP/DTP/Tdap/DT/Td)
• No vaccine or TIG is recommended for infants <6
weeks of age with clean, minor wounds
• For infants <6 weeks of age, TIG (without vaccine)
is recommended for “dirty” wounds (wounds other
than clean, minor)
• Persons who are HIV positive should receive TIG
regardless of tetanus immunization history
TETANUS: Early diagnosis by clinical features and spatula test
if positive
comprehensive Intramuscular HTIG or ATS if TIG is not available
management
Tetanus Toxoid vaccination

Metronidazole iv administration

Transfer to ICU/HDU

• Wound debridement
• Tracheostomy (if dysphagia or generalized rigidity is present)
• NGT

Control of spasms & autonomic dysfunction

Supportive care: hydration, nutrition, respiration

TETANUS: Depkes RI, 2008
Eradikasi bakteri Pembersihan luka
penyebab Antibiotik Metronidazol 15-30 mg/kgBB/hari dibagi tiap 8-12 jam; tidak melebihi 2 g/hari
Antitoksin HTG (3.000-6.000 IU /kg i.m)/ATS( 50.000 IU im & 50.000 IU iv, tetanus neonatorum
netralisasi Antitoksin kuda atau manusia 10.000 IU i.v.) ATS harus skin test
Diazepam (iv bolus) 0,1-0,3 mg/kgBB/kali i.v. tiap 2-4 jam, tetanus neonatorum dosis
awitan 0,1-0,2 mg/kgBB iv untuk menghilangkan spasme akut, diikuti infus tetesan
tetap 15-40 mg/kgBB/hari Dalam keadaan berat diazepam drip 20 mg/kgBB/hari
Kontrol spasme otot dirawat di PICU/NICU. Dosis pemeliharaan 8 mg/kgBB/hari p.o. dibagi dalam 6-8 dosis
Midazolam (iv infus/bolus)
Vekuronium Bila spasme sangat hebat pankuronium bromid 0,02 mg/kgBB iv diikuti
Terapi suportif 0,05 mg/kgBB/dosis diberikan setiap 2-3 jam
selama fase akut Sedasi Diazepam (iv bolus) /Midazolam (iv infus/bolus)/ Morfin (im/iv) /Klorpromazin
Pemeliharaan jalan napas/ventilasi Trakeostomi /Tekanan positif intermiten /Ventilasi
Penggantian volum yang cukup

Pemeliharaan hemodinamik Sedasi (seperti di atas) /Inotropik

Bila terjadi aktivitas simpatis yang berlebihan diberikan beta bloker seperti propanolol
atau alfa dan beta bloker (labetolol)
Rehabilitasi Nutrisi Fisioterapi
Imunisasi Terapi primer penuh dari tetanus
Passive immunization: HTIG vs ATS
HTIG ATS
Resource Human Equine (horse)
Need for skin test No Yes
Risk of anaphylactic Low High
reaction
Half-life 24-31 days 2 days
Risk of serum sickness - +
Prophylaxis dose 250 IU 1500 IU
Treatment dose 3000 – 6000 IU 100.000-200.000 IU
Passive immunization: HTIG vs ATS
Passive immunization: HTIG vs ATS
PHARMACOTHERAPY I- INFECTIOUS DISEASE

TETANUS
CONCLUSION
• Tetanus: forgotten but not gone
• Early diagnosis based on clinical
features is important to manage
the disease properly
• Appropriate management and
prevention can minimize morbidity
and mortality rate