Arciaga, Frances Geline R.

March 28, 2021

2MD Microbiology

Case on ANAEROBES

Chief Complaint:
10 year old boy experiencing severe muscular spasms.

History:
He was apparently well when he accidentally fell and sustained a deep wound from a rust nail that
penetrated his thigh. His mother removed the nail and cleaned the wound with soap and water. No
consultation was done. About 4 days after the incident, he initially experienced muscular spasms involving
the area of the thigh which progressed into the muscles of his jaw so that he cannot properly open his
mouth. He also noticed tonic spasms of all his voluntary muscles especially when precipitated with
external stimuli. The condition persisted accompanied by severe excruciating pain that prompted him to
consult a physician and was subsequently admitted.

PHYSICAL EXAM PERTINENT FINDINGS

 Temperature – 36.7○C  Skin: Moist
 BP –110/70 mmHg  HEENT
 Pulse rate – 120 beats/min o Inability to open mouth properly.
 Respiratory rate – 18 breaths/min o With slight rigidity of the neck.
 A fully conscious child in pain.  Abdomen: Rigid abdominal muscles
 Neurologic:
o Exaggerated deep tendon reflex.
o Muscles tense and spastic in the
extremities.
o Remainder of the exam deferred
because a patient experienced
severe pain when touched.

Questions:

1. What is the most likely organism that will cause the above infection? What are other possibilities?
Tetanus is caused by Clostridium tetani, which is an obligate anaerobic, gram-positive rod that is
motile and readily forms endospores.
 Tetanus is a disease that classically follows a puncture wound by a rusty nail but can follow skin
trauma by any object contaminated with spores.
 Although C. tetani is located everywhere, the disease is encountered largely in underdeveloped,
overcrowded, and economically disadvantaged countries. C. tetani is widespread in the feces of
domestic animals and humans, while spores of C. tetani are abundant in soil and in the environment
surrounding the habitation of humans and animals. From the localized anaerobic environment,
Clostridium tetani releases its exotoxin, called tetanospasmin and ultimately causes a sustained con -
traction of skeletal muscles called tetany.
 Tetanus is a toxemia which can reach the CNS usually appearing 4 to 5 days until 3 weeks after toxin
exposure and such is manifested by the patient wherein muscular spasm is experienced after 4 days
after the incident.
  Tetanus usually follows deep penetrating wounds where anaerobic bacterial growth is facilitated.
Three basic forms of tetanus may be distinguished: local, cephalic, and generalized. At least 80% of
the cases are the generalized form. In the adult patient, the most characteristic sign of generalized
tetanus is lockjaw, or trismus.

SYMPTOMS OF TETANUS
1. Jaw cramping 6. Changes in blood pressure and fast
2. Risus sardonicus (sardonic smile) - due to involvement of heart rate
the muscles of facial expression 7. Unaltered consciousness
3. Sudden, involuntary muscle tightening, hyperreflexia 8. Fever and sweating
(muscle spasms), spastic paralysis 9. Headache
a. Usually occurs in the stomach where there is 10. Trouble swallowing
persistent muscle contraction
4. Painful muscle stiffness all over the body which is
stimulated by the external stimuli e.g. light, air, noise)
5. Jerking or staring (seizures)

Primary Differential Diagnosis:

Strychnine Poisoning
● Strychnine is a white, odorless, bitter crystalline powder that can be taken by mouth, inhaled (breathed
in), or mixed in a solution and given intravenously. It prevents the proper operation of the chemical that
controls nerve signals to the muscles. The chemical controlling nerve signals works like the body’s “off
switch” for muscles. When this “off switch” does not work correctly, muscles throughout the body have
severe, painful spasms. Even though the person’s consciousness or thinking are not affected at first
(except that the person is very excitable and in pain), eventually the muscles tire and the person can’t
breathe.
● Trismus appears later due to the low or lack of calcium and can mimic the signs and symptoms of tetanus.
○ Strychnine poisoning develops more rapidly than tetanus and there is usually no muscle rigidity
between spasms; serum analysis for strychnine should be performed in suspect cases. But on our
case, as the patient experienced the symptoms 4 days after the incidence, this can be ruled out.
● Immediate signs and symptoms:
○ Following the ingestion (swallowing) of strychnine, symptoms of poisoning usually appear within
15 to 60 minutes.
○ People exposed to low or moderate doses of strychnine by any route will have the following
signs or symptoms:
 Agitation  Rigid arms and legs
 Apprehension or fear  Jaw tightness
 Ability to be easily startled  Muscle pain and soreness
 Restlessness  Difficulty breathing
 Painful muscle spasms  Dark urine
possibly leading to fever and  Initial consciousness and
to kidney and liver injury awareness of symptoms
 Uncontrollable arching of
the neck and back
○ People exposed to high doses of strychnine may experience respiratory failure possibly leading to
death within the first 15 to 30 minutes of exposure.
Other Differential Diagnoses:
1. Dental abscess - results in stiff jaw and mimics trismus
2. Encephalitis - occasionally associated with trismus and muscle spasms but sensorium of such patients is
clouded
3. Rabies - may present as trismus with seizures but usually the incubation period is longer.
4. Localized infection (Odontogenic or Non-odontogenic)
o Odontogenic infections: pulpal infections, periodontal infections and pericoronal infections.
o Non-odontogenic infections: tonsillitis, meningitis, parotid abscess and brain abscess.
 Both infections manifest as trismus, but the infection is usually easily detected on exam.
 The clinician should be cautious in attributing the trismus solely to the swelling,
however, as C. tetani has been found in odontogenic abscesses and the patient may
have both.
5. Dystonic reactions to antidopaminergic drugs
○ Characterized by involuntary contractions of muscles of the extremities, face, neck, abdomen,
pelvis, or larynx in either sustained or intermittent patterns that lead to abnormal movements or
postures.
○ Mental status and vital signs remain normal.
○ Causative agents: antipsychotic and antiemetics.
6. Malignant hyperthermia
○ A rare pharmacogenetic disorder triggered by depolarizing muscle relaxant (succinylcholine) and
potent volatile anesthetic agents
○ Can also cause muscular rigidity and autonomic instability, but unlike tetanus, it often causes
altered mental status and is lacking of reflex spasms
○ It should be considered in patients who recently received a causative medication.
7. Seizure
○ Although symptoms of tetanus are similar to generalized seizures, tetanus causes painful spasms
and does not produce a loss of consciousness.
8. Hypocalcemic tetany
9. Conversion Disorder (Functional Neurological Symptom Disorder)
○ Patients with this disorder present with neurological symptoms that cannot be fully explained by
a neurological condition.
○ Neurological symptoms: e.g., paralysis, muscle spasms, blindness, mutism, lump in throat,
weakness, gait disorder.
○ Hypocalcemia may produce a reflexive spasm of the facial muscles when the facial nerve is
percussed (Chvostek sign) and involves extremities more than the trunk.
○ Lab tests can rule out this.

2. Explain how this organism will cause the above manifestations. Are Laboratory findings of help in the
diagnosis of this case?

Virulence Factors
C. tetani produces two exotoxins–tetanolysin and tetanospasmin.
1. Tetanolysin is a heat-labile, oxygen labile hemolysin antigenically related to the oxygen labile
hemolysins produced by C. perfringens, S. pyogenes, and S. pneumoniae. Tetanolysin damages
 otherwise viable tissue surrounding the infection and optimizes the conditions for bacterial
multiplication.
2. Tetanospasmin (or tetanus toxin) is a heat-labile, oxygen stable, plasmid coded neurotoxin
responsible for disease manifestations. Tetanus neurotoxin is released upon cell lysis after
bacterial growth under anaerobic conditions (e.g., in deep puncture wounds). It is antigenic and is
specifically neutralized by its antitoxin. Its toxoid form is used for vaccine preparation.
 Mechanism of Tetanus Toxin
Tetanus toxin binds to polysialogangliosides receptors present on motor nerve
terminals which results in toxin internalization. Following internalization, tetanus toxin
gets transported in a retrograde way from the peripheral nervous system to the central
nervous system by retrograde axonal transport. When tetanus toxin reaches inhibitory
neuron terminals, it prevents the presynaptic release of inhibitory neurotransmitters
glycine and gamma-aminobutyric acid (GABA).

In normal condition, Glycine and GABA

released from inhibitory interneurons
induce muscle relaxation by acting on the
motor neurons and blocking excitation and
release of acetylcholine at the motor
endplate.
Lack of inhibitory signals to the motor
neurons and constant release of
acetylcholine to the muscle fibers leads to
irreversible contraction of the muscles
and spastic paralysis.
Are Laboratory findings of help in the diagnosis of this case?
● The diagnosis of tetanus is clinical and does not require a demonstration of  C. tetani. Treatment should
be started immediately based on clinical diagnosis. Laboratory diagnosis provides supportive evidence for
confirmation.
● 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. Although the laboratory findings are not diagnostically valuable, they may help exclude
strychnine poisoning.
● Specimen - Excised tissue bits from the necrotic depths of wounds are more reliable than wound swabs.
● Gram staining - reveals gram-positive bacilli with terminal and round spores (drum stick appearance or
tennis racket appearance). However, microscopy alone is unreliable as it cannot distinguish C. tetani from
morphologically similar non-pathogenic clostridia like C. tetanomorphum and C. sphenoides.
● Culture - more reliable than microscopy.
○ Robertson cooked meat(RCM) broth – C. tetani being proteolytic turns the meat particles black
and produces a foul odor.
○ Blood agar with polymyxin B: C. tetani  produce characteristic swarming growth when
incubated at 37°C for 24-48 hours under anaerobic conditions
● Toxigenicity Test - As pathogenesis of tetanus is toxin mediated, the association of the isolated organism
can only be established when its toxin production is demonstrated. Toxigenicity can be detected by both
in vitro and in vivo methods.
○ In vitro hemolysis inhibition test: C. tetani  produces hemolysis on blood agar which is inhibited
by adding antitoxin. This test indicates the production of tetanolysin only but not
tetanospasmin.
○ In vivo  mouse inoculation test: RCM broth with black turbid growth is injected into the root of
the tail of a test mouse. The test animal develops stiffness which begins with the tail and
progresses to involve the hind limbs on the inoculated side- the other limb-trunk-forelimbs.
Death occurs within two days. This test indicates the production of tetanospasmin.

3. Describe the other manifestations of the disease.

1. Opisthotonus
 State of severe hyperextension and spasticity or abnormal posturing caused by strong muscle
spasms.
 Mainly affects babies and young children because their nervous systems have not fully
developed.
 Muscle spasms will cause an individual's head, neck and spinal column to enter into a complete
"bridging" or "arching" position.
 There is also flexion of the arms and extension of the legs.
 Spasms can come on suddenly and occur repeatedly.
 Occur less in adults.
2. Autonomic dysfunction/dysregulation
 Occurs one week after the appearance of motor symptoms.
 There is tachycardia with hypertension alternating with bradycardia and hypotension.
 Dysrhythmias and diaphoresis
 Allodynia- pain sensation in light touch.
3. Cephalic Tetanus
  Rare form of localized tetanus.
 Patients with this form of tetanus present with cranial nerve palsies.
 Characterized by trismus, peripheral facial paralysis, and ophthalmoplegia which are common
due to oculomotor nerves paralysis.
 Occasionally occurs after serous otitis media.

4. What are the treatment regimens that must be initiated based on your clinical diagnosis?
Objectives of management of tetanus:
(1) To provide supportive care until the tetanospasmin that is fixed in tissue has been metabolized
i. Surgical debridement is vital because it removes the necrotic tissue that is essential for the
proliferation of the organisms. Hyperbaric oxygen has no proven effect.
(2) To neutralize circulating toxin
i. At times, very large doses of antitoxin (3000–10,000 units of tetanus immune globulin) are given
intravenously to neutralize toxin that has not yet been bound to nervous tissue. However, the
efficacy of antitoxin for treatment is doubtful except in neonatal tetanus, in which it may be
lifesaving.
(3) To remove the source of tetanospasmin.
i. Administration of penicillin strongly inhibits the growth of C. tetani and stops further toxin
production. Antibiotics may also control associated pyogenic infection.

● For muscle control spasm:

○ Benzodiazepines are preferred as they are employed clinically as sedatives-anxiolytic drugs.
Benzodiazepines increase the frequency of the chloride ion channel opening, increasing the
inhibitory effect of GABA on neuronal excitability. For children, start with doses of 0.1–0.2 mg/kg
every 2–6 hours, titrating upward as needed. Large amounts may be required (up to 600
mg/day). Oral preparations could be used but must be accompanied by careful monitoring to
avoid respiratory depression or arrest. (WHO)
○ Magnesium sulfate can be used alone or in combination with benzodiazepines to control spasm
and autonomic dysfunction. This is a physiological antagonist of calcium at the cellular level
causing vasodilatation, neuromuscular blockade and prevention of catecholamine release from
the presynaptic neurons. 5 gm (or 75mg/kg) intravenous loading dose, then 2–3 grams per hour
until spasm control is achieved. Monitor patellar reflex as areflexia occurs at the upper end of the
therapeutic range (4mmol/L) to avoid overdose. If areflexia develops, dose should be decreased.
● Metronidazole can also be used as it is active against various anaerobic bacteria and protozoa. It is
absorbed into cells, and intermediate-metabolized compounds that are formed bind DNA and inhibit
protein synthesis, causing cell death. Recommended course of treatment ranges from 10 to 14 days.
Some consider it the drug of choice in tetanus because of its safety profile and its efficient penetration
into wounds and abscesses, and negligible CNS excitation.
● Adequate fluids and nutrition should be provided, as tetanus spasms result in high metabolic demands
and a catabolic state.
5. Is there a vaccine or a drug for the prevention of this disease?
PREVENTION
Because there is essentially no immunity to tetanus toxoid, the only effective way to control tetanus
is by prophylactic immunization.
● Vaccines
○ DTaP and Tdap
■ Diphtheria
■ Tetanus
■ Pertussis (whooping cough)
○ DT and Td
■ Diphtheria
■ Tetanus
● Other medications:
○ Antitoxin such as tetanus immune globulin. However, the antitoxin can neutralize only toxin that
hasn't yet bonded to nerve tissue.
○ Antibiotics may be given either orally or by injection to fight tetanus bacteria.
○ Sedatives to control muscle spasms.
○ Other medications, such as magnesium sulfate and certain beta blockers to regulate involuntary
muscle activity, such as heartbeat and breathing. Morphine might be used for this purpose as
well as sedation.

Reference/s:
https://www.cdc.gov/tetanus/about/index.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564069/
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https://emergency.cdc.gov/agent/strychnine/basics/facts.asp
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https://www.who.int/diseasecontrol_emergencies/who_hse_gar_dce_2010_en.pdf
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