Since the 1940s, we have been abusing antibiotics, using them to treat any infection under the sun. In the short term, this worked. Our sore throats went away, our infections subsided, and we went on with our daily lives. The rash use of antibiotics to treat everything, however, has a long-term effect, one that is hitting us now: antibiotic resistance.
Antibiotic resistance is, in fact, inevitable. It’s a side effect of evolution. The arms race between a parasite and its host ensures that as one takes a step forward, the other is close behind, preparing to overtake them. But we still hold a lot of responsibility.
Our unchecked use of these drugs has allowed resistant strains of bacteria, which have been exposed to smaller, non-lethal amounts of the drug, to evolve, making antibiotics useless against bacterial infections. Doctors freely prescribing the drug to individuals with non-bacterial or mild bacterial infections, as well as individuals not fully completing a course of prescribed antibiotics or using it unprescribed, have not helped deter antibiotic resistance. Consuming animal products that have been routinely treated with antibiotics is also a huge contender.
Resistance is widespread around the globe, and affects both high and low income countries. The World Health Organisation recently released its first antibiotic resistance report, which investigated 22 countries. It showed that the proportion of bacteria that were resistant to at least one major antibiotic, ranged between 0 to 82%, depending on the country. This resistance allows previously treatable infections to become dangerous and life-threatening, with it only getting worse as bacteria frequently exchange genetic information, passing on resistance genes.
Earlier this month, however, the Scotland-based biopharmaceutical company MGB Biopharma, which is developing a new ‘’class of anti-infectives”, completed its most recent round of funding, according to the Scotsman.
New and current investors have supported the round, including Archangel Investors, Scottish Investment Bank, Barwell, and TriCapital Investors. This funding will allow MGB to move their current antibiotic contender, MGB-BP-3, to the next levels of its development, with it currently undergoing phase IIa clinical trials.
The development of a drug goes through 5 phases of clinical trials – phase 0 to phase IV, with phase IV taking place after the FDA (Food and Drug Administration) has approved the drug for general use. Drugs can take 10 to 15 years to reach phase III clinical trials alone, so the drug is still far from general use, but this funding will allow MGB to get there sooner.
The fact that the clinical trials have made it to phase II is a victory in itself, as only 14% of drugs in clinical trials are approved by the FDA for use by the general public. Phase II trials are much larger than phase I trials, involving hundreds of people, whereas phase I trials deal with between 20 to 80 participants.
The trial involves treating patients with Clostridium difficile-associated diseases with increasing doses of MGB-BP-3. C. difficile is known to be resistant to many commonly used antibiotics, which makes it an appropriate model organism for the trial.
C. difficile, is a bacterium that normally resides in the gut, and is the cause of 15-25% of all cases of antibiotic-associated diarrhoea (AAD) which can be life threatening in the elderly. AAD can occur after a patient has completed a course of antibiotics, where many beneficial gut bacteria are killed off in the process, disturbing the normal gut flora and reducing competition. This allows C. difficile to colonise the colon and release toxins, causing mucosal damage and inflammation, which results in diarrhoea. The bacteria is an opportunistic pathogen, where under normal gut conditions the bacterium is asymptomatic, and only causes a symptomatic infection due to changes in the microbiota.
Developing an antibiotic that is effective against C. difficile is a huge step in the right direction. It will not only help reduce the number of C. difficile cases and deaths (13 286 cases in the UK alone last year), but will also help pave the way for future anti-infectives that can be used to combat antibiotic resistance, and keep us as contenders in the arms race.
This article was written by Tara Gamble and edited by Miles Martin
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