Fighting antibiotic resistance from within

Finland's Ipsat Therapies has completed a Phase I trial of a novel approach to preventing bacterial resistance by de-activating antibiotics in the gastrointestinal tract.

The company presented the results of the trial, on a compound codenamed P1A, at the BioPartnering Europe (BPE​) conference in London, UK.

The annual cost for treating antibiotic resistant infections is approximately $30 billion (€25.7bn) in the USA alone, with the most common pathogens - such as methicillin-resistant Stapholococcus aureus​ (MRSA) and vancomycin-resistant Enterococci (VRE) - starting to elude even last-line antibiotic therapies.

Recently the intestine has been identified as the main source of resistant bacterial strains, due to the increased level of bacterial diversity and opportunity for prolonged exposure to antibiotics. Ipsat has now demonstrated that exposure to antibiotics in the intestine causes a depletion of natural microflora and selects for the development of resistant strains.

Earlier studies have revealed, for example, that antibiotics must be present in the intestine to allow colonisation by VRE, some strains of Klebsiella pneumoniae​ and the yeast Candida glabrata​.

The company's solution to the problem is to inactivate the antibiotic in the gut and remove the selective pressure. P1A is an oral formulation, designed to inactivate beta-lactam antibiotics in the lower intestine, after they have been absorbed into the blood. Beta-lactams are the most commonly-used antibiotics on the market today, accounting for 47 per cent of the top 10 products in a $26bn market.

The Phase I study demonstrated that P1A could remove all non-absorbed, harmful antibiotic residue from the lower intestine without interfering with therapeutic levels in serum and therefore maintaining efficacy. An excellent safety profile and efficacy was demonstrated in all patients treated with the product, according to Ipsat.

Marion Carson, managing director at Ipsat​, noted that decreased investment in the development of new antibiotics in the last 10 years has led to a reduction in the number of new antibiotics entering the market, so the current goal of the healthcare industry is to prolong the efficacy of existing therapies.

"Our goal at Ipsat is to extend the utility of current antibiotics and remove the widespread problems associated with resistance and serious infections, often fatal in a growing elderly population, and in hospitals,"​ said Carson.

Ipsat's trial also showed that after only three days of exposure to antibiotics, more than 40 per cent of the intestine's microflora are altered and some bacterial strains developed clear resistance to the antibiotic. This was evident also at the genetic level, and the changes were seen to last for the duration of antibiotic use and lasted for more than two weeks.

The next step will be a Phase IIa study to evaluate the efficacy of its lead product to prevent antibiotic-induced pathological changes in humans.