Thursday, May 31, 2007

Tuberculosis, XDR-TB and Personalized Medicine!!

After all the talking and pundits, after all the media hype and fear. XDR-TB still remains a serious issue. True there seems to be significant irony in this case and that may make it stick around a while. What is XDR-TB? Well according to the CDC

"Extensively drug-resistant (XDR) TB – or TB that is resistant to at least two main first-line drugs (Isoniazid and Rifampin) and additionally to three or more of the six classes of second-line drugs"

So why post about tuberculosis in a personalized medicine/genetics blog? The answer is simple. There must be something in the genetics of host or bacteria that create this resistance. In addition there must be a way to test for these and prevent inappropriate treatment.

This treatment is dangerous at times even causing hepatitis and liver damage. A certain subset of people cannot handle isoniazid at all. These people have a problem with Nat2 and the inactivation of this medication. These people have been well reported on in the literature and it is clear that they get significant toxic effects from the first line therapy.

Recently this year there have been many publications on the molecular identification of resistance genes.

Several genes, including

katG, inhA, kasA and ahpC, have been associated with resistance to isoniazid. Recently rpoB and katG again.

More than 90% of rifampicin-resistant strains have been shown to possess point mutations in an 81-bp rifampicin resistance determining region of the rpoB gene. This is important because
recently, non-commercial molecular methods for rifampicin and isoniazid susceptibility analysis
have been

The problem is that this method is not widespread. Even worse, there exists geographically variability in resistance not related to genotype. However this has not stopped the patenting of resistance assays. I am certain their is a buck or two to be made off of the identification and proper treatment of this life threatening disease.

The Sherpa Says: XDR-TB is bad news, but soon we will have personalized microbial resistance tests to avoid dangerous and ineffective treatment. In addition we will have pharmacogenetic tests to prevent INH toxicity. Thus giving the right bug the right drug for the right host.


Keith Robison said...

Another personalized medicine angle is that your genetics greatly influences your susceptibility to TB and leprosy (another mycobacterial disease). In the long term these genes may give important hints to mycrobacterial pathogenic behavior & therefore suggestions for therapeutic approaches.

Steve Murphy MD said...

I totally agree with you. A friend of mine Mike Murray illustrates this point in a case of community acquired pneumonia, bacterial resistance to quinolones, host susceptibility to Acute Respiratory Distress Syndrome and sepsis. I think once we have all of these pieces together we will see quite a revolution in hospital care.