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Chapter: Pharmaceutical Microbiology : Alternative Strategies For Antimicrobial Therapy

Probiotics are defined as living microorganisms that confer some health benefits when utilized in sufficient numbers. The use of harmless bacteria to replace pathogenic ones (bacteriotherapy) is not a new concept but has gained renewed interest in recent years.



Probiotics are defined as living microorganisms that confer some health benefits when utilized in sufficient numbers. The use of harmless bacteria to replace pathogenic ones (bacteriotherapy) is not a new concept but has gained renewed interest in recent years. Particularly, they have been strongly marketed as a prophylactic approach to the promotion of well-being. In addition, bacteriotherapy has been used in the treatment of a variety of gastrointestinal conditions (including diarrhoea), respiratory infections, recurrent bacterial vaginitis, recurrent otitis media, streptococcal tonsillitis and infected burns. The microorganisms most frequently used are normal components of the gut microflora and include the lactic acid bacteria such as lactobacilli, lactococci, bifidobacteria, enterococci and streptococci (see Table 27.4). Other bacteria such as Bacillus species and yeasts such as Saccharomyces may also be utilized. Since each of these organisms possesses different characteristics and requirements for growth it is likely that they do not have a common mechanism of action.



A)  Gastrointestinal Conditions


Probiotics for oral administration are marketed as dairy products such as yoghurt drinks, but also as powders, tablets or capsules. Irrespective of the nature of the product, there is a need to consume in the region of 109–1011 microorganisms in order to bring about any effect. A number of studies have highlighted issues of inconsistency in the content of viable microorganisms within various products. The precise manner in which probiotics bring about their health benefits is unclear, but a prerequisite property is the ability to colonize the gut. The orally administered organisms must first, therefore, be able to survive passage through the stomach acid and then compete with the indigenous flora in the intestine. A competitive edge will be provided by the ability to colonize the gut wall and the capacity to produce bacteriocins. Probiotics have been administered rectally to overcome the necessity for acid tolerance, but there is a risk of spreading faecal pathogens.


Probiotics have been found to be of benefit in the treatment of infectious diarrhoea in children. When used as a supplement to breast milk in premature infants they were found to reduce the incidence and severity of necrotizing enterocolitis. A recent review summarizing the available clinical trial data has suggested value in the treatment of ulcerative colitis, but the results for Crohn’ s disease were disappointing and the authors stated that the use of probiotics could not be recommended on the available evidence.


Clostridium difficile is a Gram positive, spore-forming anaerobic rod which, in certain conditions, can overgrow in the intestinal tract and produce toxins causing diarrhoea and damage to the epithelial lining of the gut. This condition is a particular problem in elderly hospitalized patients who have received courses of broad-spectrum antibiotics. Since the colitis is caused by overgrowth of a pathogenic bacterium in the intestinal tract it would seem to be potentially amenable to probiotic treatment. However, a recent Cochrane review of the current clinical trial data found that only treatment with Saccharomyces boulardii had any significant effect. Many hospitals use a range of commercially available probiotic yoghurt preparations but the effectiveness of these is currently unproven.


B)   Infected Burn Wounds


Burn wounds are devoid of microorganisms immediately after the injury has been sustained, but fairly quickly thereafter they will become colonized with microflora from the adjacent intact skin and also by environmental microbes. These bacteria are mainly Gram-positive coagulase-negative staphylococci, but they may be gradually replaced by more harmful Gram-negative bacteria such as Ps. aeruginosa and Acinetobacter spp. over the following few days. These bacteria are notorious for being highly antibiotic resistant and they flourish, often forming biofilms, because the usual defensive properties of intact skin are no longer present. Colonization with these organisms delays healing, can inhibit grafting and may lead to systemic infection. Studies have shown that applications of Lactobacillus plantarum were as effective as silver sulphadiazine in the management of infected burn wounds. This may be of relevance in those countries where the costs of conventional antibiotic treatment are prohibitive or where there is a high level of antibiotic resistance.


C)  Recurrent Vaginitis


Many women suffer from vaginitis, caused by either bacteria or Candida albicans, which may lead on to urinary tract infections. In these cases the normal vaginal microflora which comprises mainly lactobacilli is overrun by various other, sometimes pathogenic, bacteria or fungi. The usual approach to treatment is the administration of antibiotics, but recurrence is commonplace. The vaginal administration of probiotic cultures has proved to be beneficial in these cases; however, strains of bacteria isolated from dairy products are not always suitable. The lactobacilli should be those that have the capacity to bind specifically to vaginal epithelial cells.


D)  Acute Otitis Media


This is a very common condition in young children in which bacteria normally present in the nasopharynx transfer via the eustachian tube into the middle ear. The predominant bacteria are Streptococcus pneumoniae and Haemophilus influenzae. Antibiotic therapy is frequently unsuccessful and recurrences are common. As we have seen in the examples outlined above, the picture is once again one of undesirable bacteria replacing normal commensal flora and causing disease. Studies have been reported in which children were treated with suspensions of α-haemolytic streptococci sprayed into the ear to inhibit the growth of the invading pathogens and recolonize the infected site. The results showed that the treated patients had significantly better outcomes than the placebo group.


Some workers have highlighted the fact that probiotics should be used with caution in those patients whose immune system is impaired because there have been reported incidences of invasive infections occurring in immunocompromised adults. In addition, Lactobacillus bacteraemia has been reported following probiotic therapy in two children who had received multiple courses of antibiotics and who were suffering from other serious underlying conditions.


The currently available data suggest that probiotics may have some value in certain selected conditions, but a great deal more background scientific information is required before this can be moved forward substantially. The approach of using a single culture for a whole spectrum of conditions is untenable. It is clear that the probiotic bacteria will act in a variety ways, producing arange of interfering substances and having different abilities to adhere to epithelial cells. Individual cultures may therefore need to be developed for use in specific conditions and once this has been achieved large-scale trials are needed to verify their value.


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