Clostridial Infection

These are anaerobic, Gram-positive, spore-forming rods widely distributed in nature, particularly in soil. They form resistant spores under stress. These spores which can survive brief heating to 100 degrees C, and the powerful exotoxins the active bacteria produce are central to the medical importance of the species.

A rapidly spreading (up to 2cm/hr with death in 12hrs) skeletal muscle infection usually caused by Cl. perfringens (also known as Cl. welchii), a toxin and gas-producing species.
Under anaerobic conditions in deep necrotic, contaminated wounds, spores germinate and the bacteria proliferate. The toxins causing tissue necrosis then spread. Host and local wound factors are important, as although 90% contaminated wounds may have clostridia, only 2% develop clostridial myonecrosis. Thus a common disease of war if rapid evacuation and treatment facilities inadequate, but also seen in:

• Intravenous drug-abusers
• After surgery; particularly associated with peripheral vascular disease, diabetes and immunocompromise
• Increasing numbers of non-traumatic, spontaneous cases¹

Symptoms

• Severe pain, often sudden onset, disproportionate to signs

Signs

• Myositis
• Myonecrosis
• Oedema
• Palpable crepitus due to gas formation
• Mottled overlying skin, with little inflammation
• Severe toxicity, tachycardia and hypotension disproportionate to fever

Treatment

Hyperbaric oxygen², with surgical debridement to remove infected and dead tissue.
Give antibiotics (penicillin) and consider antitoxin.

Prevention

Much rarer since antibiotic prophylaxis in routine bowel surgery.

Clinically, it appears similar to gas gangrene, now rare in UK, with the legalisation of abortions. Formerly the leading cause of maternal death worldwide, still a problem in developing countries, due to illegal abortions and poor obstetric practice.^3,4,5 2 major factors involved:

• Infection, which is commonly caused by Cl. perfringens in mixed infection with non-sporing anaerobes (eg Bacteroides species), Group B Beta-haemolytic streptococci, staphylococci, or E coli, N. Gonorrhoea, Chlamydia Trachomatis and Mycoplasma.
• Retained products of conception

Always caused by Cl. tetani. The effects are mediated by exotoxin tetanospasmin. Spores are highly resistant and widespread in soil, house dust, etc. Having gained entry spores can remain in normal tissue for months or years.
May be generalised or regional e.g. cephalic⁶Intrathecal tetanus immunoglobulin⁷ or baclofen may be used, though they are not always effective.⁸

Caused by toxins of Cl. difficile. The highly resistant spores are difficult to eradicate from a hospital environment, and a high level of contamination greatly increases the risk of colonisation of the colon by this clostridium, particularly if prescribed antibiotics.

Risk Factors

Up to 20% hospital patients may be asymptomatically colonised.⁹ The elderly, immunosuppressed, and those convalescing from bowel surgery are particularly vulnerable.

Presentation

• Normally presents with watery diarrhoea, fever, and abdominal cramps within a month of receiving antibiotics.
• More rarely progresses to severe colitis, with pseudomembrane formation, and even toxic megacolon and perforation.
• Antibiotics such as cephalosporins and and clindamycin, not only disrupt normal colonic bacteria, but in having a sub-lethal activity against Cl. difficile, provoke toxin production. Trimethoprim and ciprofloxacin, in having little effect on toxin production, are less likely to cause problems, though virtually all antibiotics have been reportedly associated with Cl. difficile infection.

Investigation

Sigmoidoscopy with biopsy reveals characteristic mucosal changes.

Treatment

• Stop unnecessary antibiotics
• Rehydration
• Bland diet
• Severe cases may require metronidazole (vancomycin in resistant cases).¹⁰

25% recurrence rates in hospital, usually with a different strain.

Prevention

Primary prevention:

• Guidelines for use of antibiotics
• Infection control procedures, particularly handwashing by healthcare staff
• Patient education regarding handwashing
• Environmental cleaning, particularly toilet areas

Secondary prevention (prevents cross-infection during an outbreak):

• Isolation rooms with en-suite toilet facilities. The patient can leave isolation once asymptomatic.
• Hand decontamination for both staff and patients.
• Use of disposable gloves and plastic aprons for the care of patients with diarrhoea.
• Daily cleaning to reduce spore load in the environment, particularly linen and patient equipment. Spores of Clostridium difficile are resistant to many common cleaning agents and some have even been shown to promote spore formation. The best agent for cleaning is not known.
• It may be necessary to restrict admissions to the unit.

Caused by neurotoxin of Cl. botulinum. Occurs in 3 main circumstances, to which must now be added the threat from bioterrorism.

Foodborne

Commonly occurs following consumption of contaminated preserved food, particularly in countries where home preserving is practiced. Failures in the anaerobic processes of canning and fish smoking are common culprits. It can also develop on cheese and sausages at room temperature for long periods. Although the spores can resist 2 hours boiling, the toxin is rapidly destroyed at normal cooking temperatures.

Presentation

Presents as sudden, severe weakness within few hours to days of ingestion, associated with nausea and diarrhoea.
Characteristically there is blurring of vision with dilated unreactive pupils. Cranial nerves preferentially affected, followed by symmetrical descending paralysis,leading to respiratory failure, with a mortality rate of 25%.

Treatment

Trivalent antitoxin as soon as possible, as binds irreversibly like tetanus toxin. Full supportive treatment, which may require prolonged ventilation, as recovery is dependent on formation of new neuromuscular junctions.
Wound botulism: Follows contaminated wounds, though increasingly is seen in intravenous drug-abusers using black tar heroin.^11,12 Similar picture to foodborne, though without gastrointestinal symptoms, and incubation longer at about 10 days.

Infant botulism

It develops in susceptible infants following bowel colonisation. Environmental factors and ingestion of honey are associated factors.¹³ Above the age of one, gastric acid, secretory immunoglobulins, and a more mature bowel flora prevent germination of spores.

Presentation

Presents as constipation before development of motor function symptoms, with same spectrum of descending paralysis.

Treatment

Human botulism immune globulin¹⁴

Differential Diagnosis

• Spinal muscular atrophy¹⁵
• Metabolic disorders
• Other infectious diseases

Patients usually recover, because infants rapidly grow new nerve endings. Mortality rate of 1%.

Bioterrorism

The most toxic substance known to man¹⁶; a lethal dose <1mcg.
The Germans were developing the toxin in WWII as a cross-channel weapon, and the death of the head of the Gestapo in 1942 was attributed to a hand grenade contaminated with toxin, supplied to the Czech patriots by the British.
A deliberate release may involve airborne dissemination of toxin, or contamination of food or water supplies with toxin or bacteria.
Water treatment inactivates the toxin, the toxin cannot penetrate intact skin, and it loses activity within a few days.
The most likely scenarios would therefore be:

• A deliberate contamination of foodstuffs; large doses may lead directly to neurological symtoms without the gastrointestinal symptoms of nausea, vomiting, and diarrhoea followed by constipation.
• Aerosol release; most effective in an enclosed environment. After inhalation, the onset of symptoms may be as rapid as <1 hour. However, in cases of accidental inhalation symptom onset can be 3-4 days.

Botulism should be considered in an apyrexial patient with full sensory awareness and a bulbar palsy, with descending paralysis.¹⁷

Fourth commonest form of food-borne illness, after Norwalk-like viruses, Campylobacter, and Salmonella.

• Spores survive cooking, and germinate during slow cooling or unrefrigerated storage.¹⁸ They produce exotoxin, requiring a large infective dose.
• Mostly associated with meat and poultry, usually occurring in schools, hospitals, factories and catering establishments.Typically, a meat dish is stewed or boiled and allowed to stand for 4-24 hours and then served without adequate reheating.
• 6-12 hours later the patient suffers crampy abdominal pain followed by diarrhoea, which subsides 12-24 hours later.