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UK firm developing nasal MRSA gel

By Gareth Macdonald , 21-May-2008

XF-73, a new gel-based bacteriocidal drug being developed by UK biotechnology firm Destiny Pharma, could represent a significant advance in the battle against bacterial resistance.

In trials conducted to date, XF-73 was able to kill five of the most virulent strains of the community/hospital acquired bacterium methicillin resistant Staphylococcus aureus (MRSA), including the NRS 382 serotype which is the most prevalent in the US. More importantly, the compound failed to induce resistance in any of the MRSA strains after 55 serial passages (exposure of the drug to 55 generations of the organism), which Destiny believes is the longest bacterial resistance study to have been conducted by any pharmaceutical company to date.


MRSA causes around 126,000 hospitalisations and 19,000 deaths in the US each year. MRSA's resistance to bacteriostatic beta-lactam-based antibiotics, coupled with its enhanced virulence and capacity to cause toxic sepsis, means that the infections it causes are difficult to treat and highly transmissible, particularly among immunosuppressed hospital patients. In response to the issue health protection agencies worldwide have established various programs designed to eradicate MRSA. In the UK, where the bacterium was first identified in 1961, the government has focussed on improving hospital cleanliness standards and reducing the risk of patient to patient transmission by National Health Service staff.


However, while these efforts showed early signs of success, cases of MRSA infection in the country rose 0.6 per cent to 1,087 in 2007, according to data released by the Health Protection Agency. The UK's Department of Health said that it would maintain "a close watch" on all emerging findings regarding the "superbug." XF-73 is the most advanced of Destiny's range XF bacteriocides. In contrast with bacteriostatic antimicrobials that simply prevent the growth of bacteria, bacteriocides kill such organisms by puncturing them. XF-73 is a porphyrin derivative that adheres to bacterial cell walls via an electrostatic interaction, subsequently releasing a lethal oxygen radical when activated by light.


In addition, because XF drugs stick to the prokaryotic cell in a non-specific manner, rather than via interaction with the specific molecular receptors like traditional antibiotics, they are much less likely to encounter bacterial "escape mutants" with which they cannot interact. This reduces the likelihood that any surviving organisms have done so as a result of any inherent resistance to XF-73. In vitro, XF-73 has demonstrated activity against a wide range of bacterial species, including clinically-significant Gram-positive organisms such as Staphylococcus epidermidis, Clostridium difficile and Propionibacterium acnes.


Additionally, data from a Phase I trial, presented at this years European Congress on Clinical Microbiology and Infectious Diseases (ECCMID) meeting in Barcelona, Spain, indicated that the drug was able to significantly reduce the occurrence of MRSA infections when applied to the nasal passages of trial subjects, as XF-73 was able to act as effective barrier. Plans for further Phase I trials are now being drawn up. Destiny Pharma commented that "results suggest that XF-73's remote resistance profile may allow widespread MRSA decolonisation in hospitals."


In response, Derek Butler, chairman of UK group MRSA Action told the BBC that while XF-73 was an interesting development "more tests need to be done on it. We need to be careful in saying we have beaten the resistance problem," adding that "bacteria have a habit of being able to get round any treatments we develop."

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