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Hard-to-kill bacteria or “superbugs” have become a major problem for hospitals. Between 5% and 12% of hospital patients in the EU are thought to acquire an infection during their stay, with
many caused by bacteria such as _Clostridium difficile_ (_C. diff_) that are resistant to antibiotics. In the US, _C. diff_ is the leading cause of hospital-acquired infections and, in the
UK – although it is declining – it remains a major healthcare problem implicated in thousands of deaths every year. But a group of researchers believe they may have found a surprising answer
to treating _C. diff_: giving patients another dose of the bacterium. The effects of _C. diff_ range from mild diarrhoea to more serious and life-threatening conditions such as
pseudomembraneous colitis (inflammation of the intestines) and toxic megacolon, which often require surgery to remove the affected tissue and can be fatal. Despite being a major human
pathogen, _C. diff_ is actually part of the normal group of microorganisms found in the gut (in 3% of healthy adults). But sometimes it takes advantage of disruptions in our bacterial flora
to cause disease. These changes are typically caused when antibiotics are used to treat an unrelated condition, killing off the protective microorganisms of our gut and allowing _C. diff_ to
flourish. Paradoxically, more antibiotics are typically used in an attempt to kill off the _C. diff_ as well. However, this can create the same problem again, leading to a recurrence of the
infection in approximately 30% of cases. And once the infection has recurred once, it recurs again in 60% of cases. This has led doctors to consider many alternative strategies. Giving
patients bacteria thought to promote a healthy digestive system (probiotics) has been tried as a way of replacing the normal gut flora killed by antibiotics, but with little evidence of
success. More recently, trials have begun with the more controversial “faecal transplants”. Both selected bacteria from the faeces of a healthy donor and entire samples faecal matter have
been implanted in a patient’s colon to test the idea. There is a growing body of evidence to suggest this can provide both resolution and protection from recurrence. Researchers from Loyola
University Health System in Illinois have now published a trial of a technique that could be described as a more refined and specific version of probiotic treatment or faecal transplant.
Rather than replacing the entire gut-flora of an individual, the researchers introduced a different, harmless strain of _C. diff_ that doesn’t produce any toxins. Having already conducted an
initial trial, the researchers expected that the non-toxic bacteria would outcompete the toxic strain and prevent the progression and recurrence of infection. The latest trial demonstrated
the safety of the treatment and presented further evidence for its efficacy. The most effective dose of bacteria reduced the rate of recurrence to 5%, compared to 30% in a placebo group.
This is an extremely encouraging result. The next stage in the translation of this into the clinic is a phase III trial which will determine the efficacy and safety over many thousands of
diverse patients. If successful this could lead to an incredible, cost-effective and widely applicable treatment. Further work is needed to understand why and how this non-toxic strain
outcompetes the toxic strains in the gut. There is a cautionary note, however. _C. diff_ has been shown to transfer its DNA (containing the toxin genes) from toxic strains to non-toxic
strains in the laboratory. If the non-toxin strain is inherently more fit in the human gut than the toxic ones, and if it could readily acquire the toxin genes and become a fitter toxic
strain, we may head straight back to square one. This would add yet another, even more dangerous superbug to the ever-growing list.