The anti-viral activities of bismuth in the treatment of gastroenteritis
Bismuth exhibits a significant inhibition of viral invasion of host cells, as well as viral efficacy. When ingested orally, bismuth reduces norovirus RNA levels. The antiviral activity of bismuth has been shown to inhibit the replication of four strains of the rotavirus when tested in tissue culture cells, resulting in a dose-dependent reduction in the growth of many enteric viruses. A recent study demonstrates that bismuth also has a high potency against the novel severe acute respiratory syndrome coronavirus 2.1,2,3
Asignificant reduction in the severity, the duration of abdominal cramps as well as in the median duration of gastrointestinal (GI) symptoms, have been observed in a trial involving patients inoculated with the norovirus (also referred to as the Norwalk virus) and treated with bismuth, compared to those in the placebo group.4
Role of bismuth in the management of viral gastroenteritis
Bismuth is an effective agent in the management and treatment of viral gastroenteritis and is available in South Africa as a combination product, known as Kantrexil®.5
Kantrexil is a unique combination of kanamycin (an antimicrobial) and bismuth (a gastro-protection agent), which makes for a more economical and effective treatment.5
Causes of gastroenteritis
Viral gastroenteritis – also known as acute enteritis or enteropathy – is a common illness seen around the world. Various different pathogens may cause the symptomatology of the illness, though in routine practice the true causative agent is generally not identified.6,7,8,9
It is known that several different viruses including rotavirus, norovirus, adenovirus as well as astroviruses all account for most cases of acute gastroenteritis. The aetiology of acute gastroenteritis is attributed to many infectious agents as summarised in Table 1.10
Identifying the exact incidence and cause of acute infectious gastroenteritis is often a difficult task as not all patients report their symptoms or seek medical care. Most viral causes of acute gastroenteritis are dominated by the rotavirus and the norovirus. It is known that the rotavirus causes particularly severe dehydration. Diarrhoeal episodes along with nausea and vomiting may cause severe fluid and electrolyte loss resulting in severe dehydration and even death.11
Patients with mild gastroenteritis seldom seek medical intervention, using over-the-counter (OTC) medication for symptomatic relief. When a patient visits the doctor, they may have already self-medicated, but usually require higher-level treatment – especially in South Africa.
Classification of bismuth
Bismuth is classified as a non-proprietary monograph and an anti-diarrhoeal and ant-acid agent. It acts by decreasing the flow of fluids as well as electrolytes into the bowel. The agent reduces inflammation in the GI tract, and works by killing organisms, which may cause gastroenteritis.12
Table 1 summarises the most common viral pathogens, which cause gastroenteritis. Of these, norovirus, rotavirus, as well as coronaviruses, are the most prevalent pathogens that cause viral gastroenteritis. Bismuth has demonstrated proven efficacy against norovirus, rotavirus, as well as coronaviruses.10
Indications and efficacy
Bismuth is indicated for the symptomatic treatment of nausea, indigestion, an upset stomach, diarrhoea as well as other temporary discomforts of the stomach and GI tract.13
When administered orally, more than 99% of ingested bismuth is excreted in the faeces with a negligible quantity absorbed into the bloodstream, allowing for its local mechanism of action.12
Bismuth has no effect on normal gut flora. The agent has been shown to prevent pathogenic bacteria from binding to mucosal cells. Furthermore, bismuth prevents intestinal secretion and fluid loss, promotes fluid and electrolyte reabsorption, reduces GI inflammation, and promotes the healing of pre-existing ulcers in the stomach.13
Bismuth also inhibits the adhesion of Helicobacter pylori to the gastric epithelial cells and blocks the bacteria’s enzyme activities, including phospholipase, protease, and urease.13
Along with demonstrating great antiviral activity, bismuth demonstrates antimicrobial activity against a number of pathogenic bacteria among OTC agents.14-17
A study has shown that bismuth decreased the invasiveness of enteropathic bacteria within GI cells. The electron-dense deposits of bismuth found within Yersinia enterocolitica cells, clearly indicated that the antibacterial effect of the agent is attributable to its ability to increase permeability of the bacterial cell wall, thus increasing bismuth concentrations in bacterial cells.18,19
Another study demonstrated that bacteria exposed to bismuth resulted in a loss of membrane integrity, as well as the inactivation of cellular adenosine triphosphate (ATP) synthesis, resulting in the death of the microorganism.20
In vitro studies have verified the antimicrobial effect of bismuth on pathogens such as Escherichia coli, Salmonella as well as the norovirus.17
Bismuth has been shown to reduce bacterial growth, with C. difficile proving to be the most susceptible. Bismuth is a safe and effective agent, which is commonly given for the treatment of traveller’s diarrhoea as well as enteric infection.21-27
It is clear that bismuth is a beneficial agent for patients at risk or those suffering from gastroenteritis. As the agent is not absorbed systemically, it is a safe and effective agent for use in both infants, children, and adults. Bismuth subcarbonate, found in Kantrexil, demonstrates a low absorption (<1%) from the GI tract (GIT). With <1% absorbed systemically, bismuth is able to continue working locally along the entirety of the GI tract as opposed to systemically absorbed agents that exit in the GI tract and enter the system, moving away from the site of the infection and into the bodies tissues and metabolic processes.21
This low systemic absorption, therefore, allows for almost no systemic side effects or cross-resistance as well as drug-related interactions and allows for less consideration of kidney and liver function issues so typical of systemic treatment – very safe and 99% available at the site of the infection.21
Conclusion
Kantrexil is a highly effective agent which contains a combination of antimicrobial (aminoglycoside which has almost no systemic absorption), adsorbent (to adsorb toxins in the GI tract), a protective layer, and demulcent (to relieve inflammation), an all-in-one combination. Combining these active ingredients results in a more cost-effective treatment when compared to prescribing four or five separate medications.21
References
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