Extensively Resistant Tuberculosis: A Ray Of Hope Is Announced In Berlin - Breakthrough By German And Italian Researchers

Main Category: Tuberculosis
Also Included In: Respiratory / Asthma;  Infectious Diseases / Bacteria / Viruses
Article Date: 06 Oct 2008 - 1:00 PDT

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Although the dreaded extensively resistant tuberculosis is already advancing on us and doctors have been unable to save a number of sufferers, a new, promising treatment based on linezolid has been successfully trialled by German and Italian researchers.

They presented their preliminary results to the Annual Congress of the European Respiratory Society (ERS) in Berlin.

The classical treatment scheme for tuberculosis theoretically cures approximately 80% of patients. Yet some two million people are still dying of the disease each year! This alarming situation is caused in part by the complexity and length of the treatment, which have gradually led to the emergence of TB strains that resist classical treatments and, increasingly, the other strategies used by doctors.

Following cases of individual resistance to one or other antibiotic, certain bacilli have developed resistance to a number of drugs and are thus known as multidrug-resistant bacilli or MDR-TB. More recently, other strains, labelled extensively resistant or XDR-TB, have been found to resist even the most powerful anti-TB drugs and cause very high death rates among infected patients.

Little doctors can do

Patients stay in hospital two and a half times as long, the treatment period is doubled and, worst of all, the death rate is five times higher than for the already hard-to-treat MDR-TB. This is the shocking reality of XDR-TB, which is increasingly prevalent worldwide, with some strains already on our borders.

Last February, the World Health Organisation (WHO) announced that 45 countries had already reported at least one case of extensively resistant TB diagnosed on their territory since 2002. Ten of those countries were either located within Europe or bordered directly on Europe.

Not only do the XDR-TB bacilli resist the two most potent first-line antibiotics (isoniazid and rifampicin), which are also resisted by MDR-TB; they also hold out against all quinolones and at least one of the three injectable antibiotics used in second-line treatment (amikacin, capreomycin and kanamycin).

The WHO report also states that, out of an annual total of nine million diagnosed cases of TB, there were 500,000 cases of multidrug-resistant strains and 40,000 extensively resistant cases. The countries of the former Soviet Union, Japan, the Republic of Korea and South Africa have the highest levels of MDR-TB and XDR-TB.

There is little doctors can do to deal with this situation, hence the pressing need to develop new anti-TB drugs and the interest in all potential treatment options.

Pleasing results

So the scientific presentation to the ERS Congress in Berlin is a welcome ray of hope.

A team of German and Italian researchers, led respectively by Christoph Lange (Research Center Borstel) and Giovanni Battista Migliore (Fondazione Salvatore Maugeri, Tradate) set out to study the potential for using linezolid, an oxazolidinon-type antibiotic, on patients with laboratory-documented multidrug-resistant or extensively resistant TB.

This was a considerable challenge, since linezolid is not designed for this type of treatment and there was a serious shortage of data on the drug's safety and effectiveness.

As the researchers explained in Berlin, they started by analysing the 7,026 TB cases diagnosed in Germany and Italy from 2004 to 2007, from which they were able to identify 265 multidrug-resistant and 17 extensively resistant cases.

Linezolid treatment was provided to 82 and 7 patients respectively as part of this original study.

The new protocol gave very pleasing results, as could be seen from the figures presented at the ERS Congress by Lange and Migliori.

In three-quarters of cases (67 out of 89), linezolid eliminated TB bacilli in sputum and sterilised cultures. Out of the 67 patients for whom the bacilli were thus eradicated, the team were able to obtain the final treatment results for 38, and found that full clinical success had been attained in 31 of those cases, or over 80%.

Historic breakthrough

Everything has its cost, and Lange and Migliori reported that this pleasing clinical success was, unfortunately, accompanied by a relatively high level of side-effects, identified approximately two months later in one-third of the patients. These included severe anaemia and polyneuropathy. In 25 cases the treatment even had to be stopped.

"But all of these effects were reversible and there were no linezolid-related deaths", Lange emphasised in Berlin.

Yet there is some good news to lighten up this rather sombre picture: the side-effects seem to be less significant in extensively resistant TB than in the multidrug-resistant form (14% compared to 38%).

The breakthrough announced at the ERS Congress is certainly a historic one since the effectiveness of linolezid treatment has now been proved for multidrug-resistant TB and even more so for extensively resistant TB, which is becoming a major menace.

The next step is to determine the best regimen for its administration in order to minimise side-effects that might make it necessary to abandon the treatment, and in this way to ensure that the new protocol's success is compromised as little as possible.

European Respiratory Society

European Respiratory Society Annual Congress