Thursday, 15 September 2011

Advance in Prevention of Medical Implant Infections

Medical implants such as heart valves and catheters commonly fail because of fungal infections of the implant which form a biofilm - a thin viscous layer that forms on the surfaces of the device which resists the absorption of antifungal drugs and therefore effectively protects fungi growing within the film.
This is a major cause of failure of these devices and often require the surgical removal of the device in order to clean up the infection. Mortality following some types of infection is as high as 30% so this is a highly important issue for both doctor and patient.

Robbins et. al. have discovered an effective treatment target that may effectively prevent the ability of biofilms to protect the fungus in the future. Heat shock protein (Hsp90) has already been directly implemented in drug resistance and here it is shown that if the amount of Hsp90 expression in the fungus is reduced then biofilm formation is greatly reduced and resistance to antifungals also prevented.

Yeasts are the most common infecting fungus in this situation. Once the expression of Hsp90 was prevented by genetic deletion it became vulnerable to antifungal treatment by the azole group of antifungals.

Aspergillus is the most lethal infecting organism in this situation, but once Hsp90 expression had been prevented it became more vulnerable to treatment with the new echinocandin group of antifungal drugs.

This study used isolates of fungi that had had Hsp90 expression genetically altered and also tested the effect of treating infections in mice with drugs that inhibit Hsp90. This research suggests that if we could develop new drugs to downregulate Hsp90 expression (or possibly even use existing drugs if appropriate e.g. if toxicity is low) then we could treat infections using a combination of Hsp90 inhibitor and antifungal to bring about a much more effective elimination of the fungal infection, hopefully without the need for surgery.

Hsp90 inhibitors already exist that may be directly testable in human experiments so perhaps we will see a  introduction of this technique in the not to distant future.

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