New drug to combat antibiotic resistant bacteria

6 November 2014

A Dutch biotech company has release news of patient trials of a new treatment for methicillin-resistant Staphylococcus aureus or MRSA.

Presenting results at the Antibiotic Alternatives for the New Millennium meeting in London yesterday, firm Micreos reported data from a small patient trial of Staphefekt™, a bactericidal enzyme derived from bacteriophages (viruses that infect bacteria) in six patients with MRSA skin infections.

The new drug specifically targets Staphylococcus aureus and is said to be ‘equally effective in killing methicillin-resistant Staphylococcus aureus (MRSA) as methicillin-susceptible Staphylococcus aureus (MSSA)’.

Importantly, the mechanism of action is different from that of current antibiotics. The endolysin enzyme is said to target the bacterial cell well to cause lysis (bursting and bacterial cell death), but via a cell wall component that is less susceptible to change from genetic mutation and the resulting development of antibiotic resistance than that targeted by current drugs.

The endolysin is a genetically engineered form of the bacteriophage enzyme. Clinical microbiologist Bjorn Herpers explained: “Endolysins exist in nature, but we’ve made a modified version that combines the bit that is best at binding to the bacteria with another bit that is best at killing it”.

The mechanism of action is specific to S. aureus, meaning that it would have limited efficacy in the case of mixed pathogenic bacterial infections (requiring the use of additional drugs to kill other pathogenic bacterial species), but would also not kill harmless or beneficial bacteria.

Micreos CEO Mark Offerhaus said: “With the introduction of Staphefekt™, we enter a new era in the fight against antibiotic resistant bacteria, targeting only the unwanted bacteria. This is a far more logical and elegant approach. Millions of people stand to benefit. That’s very exciting and gratifying”.

Whilst further, larger trials of the drug (and publication of results) will be essential, it is nevertheless being enthusiastically greeted as a potentially pivotal development in efforts to combat antimicrobial resistance (AMR). Whilst this phenomenon currently accounts for thousands of deaths annually in the UK, further spread could dramatically increase this figure, a realistic scenario underpinning recent new efforts to combat AMR.

It may be that personalised medicine will come to encompass infectious disease control, as the capacity for rapid, precise diagnosis using microbial genomics is combined with narrow-spectrum, precisely targeted antibiotics.

However, even assuming its success can be replicated in larger trials, the endolysin treatment has a major limitation to overcome, being currently only available in the form of a cream for topical application suitable for treating skin infections; it is reported that the firm hopes to develop a tablet or injectable form although this may prove to be a greater challenge.

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