MDR/XDT TB and Carbapenem

The ‘White Plague’, or as it is commonly known Tuberculosis (TB) is making a comeback in not only the rest of the world, but in North America as well. HIV is helping the spread, an immuno-compromised patient be more susceptible than a healthy person.
In 2009, it was estimated by WHO that there were 9.4 new cases of TB. 3.3 % of these new cases (approximately 250,000 patients) had Multi Drug Resistant (MDR) TB. The criteria for a TB strain to be classified as MDR is to be resistant to the traditional treatment of isoniazid and rimfampin. In 2008, MDR was estimated to have killed 150,000.
To make matters worse, an even more strain strain has emerged, Extensively Drug-Resistant (XDR) TB. This strain is not only resistant to isoniazid and rimfampin, it is also immune to a fluoroquinolone and resistant to injectable amikacin, kanamycin or capreomycin.
With the exception of fluoroquinolones, there hasn’t been any new anti-TB antibiotics introduced for treatment.
TB was one of the first organisms that penicillin was not able to treat. The causative organism of TB, Mycobacterium tuberculosis, naturally produces a chemical called beta-lactamase which inhibits the active ingredient of penicillin, beta lactam, from working.
Recently though, researchers (http://www.einstein.yu.edu/home/news.asp?id=305 ) found that by combing two different drugs together, XDR TB could be killed in a laboratory setting. These two drugs were Clavulanic acid and meropenem ( a Carbapenem) .
Clavulanic acid by itself has no therapeutic effect. What it does do is neutralize beta-lactamases produced by bacteria. Unable to destroy the beta-lactam of the antibiotic, drugs such as penicillin can destroy the bacteria.
When Clavulanic acid is combined with a meropenem (a beta-lactam antibiotic), they can effectively destroy TB in a lab setting, but can they be used in a clinically setting?
In 2010, Belgium doctors treating a 14-year-old girl from Chechnya with XDR-TB with answered that question. With no other options to treat the acutely ill and malnourished patient, Clavulanic acid and meropenem produced positive results in eleven weeks. (http://www.stoptb.org/news/stories/2011/ns11_035.asp)
This is indeed positive news, but some cold realities have to be faced.
First of all, these drugs have to be administered intravenously. That not only requires an infrastructure to be put into place to provide patients this service, there is also the risks associated with long-term I.V. therapy (ie infection).
Secondly, there is the cost of these drugs.
Thirdly, clinical studies will have to be done to prove it’s effectiveness.
Finally, there is the possibility that resistance may develop to this combination. After all meropenem has recently been found to b useless against New Delhi metallo-beta-lactamase-1 (NDM-1) an enzyme at produces undetectable resistance to Beta-lactam drugs.
But hopefully this will prove to help with the global fight against TB.