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Old drugs provide new hope for TB

A third of the world’s population is infected with the bacteria that causes TB. Credit: Shutterstock/ Kateryna Kon
A third of the world’s population is infected with the bacteria that causes TB. Credit: Shutterstock/ Kateryna Kon

A group of old antibiotics could be the answer to drug-resistant tuberculosis (TB) and trials have already been completed.

Every hour, around five people in Europe die from TB, and about a third of the world’s population is infected with Mycobacterium tuberculosis, the bacteria behind TB, according to the World Health Organization (WHO).

Most infected people manage to keep the disease in check. However, rising drug resistance and poverty means that 1.5 million died from TB in 2013, making it second only to AIDS as the most deadly single infectious agent worldwide.

In 2013, around half a million people were diagnosed with multi-drug-resistant tuberculosis, the WHO said.

Developing new antibiotics which the TB bacteria has not had time to develop resistance against is a slow and expensive process. The advantage of repurposing old drugs to fight new diseases is that they have already been shown to be safe, cutting development time from 10 to five years.

‘We are trying to revive an old antibiotic to treat serious infections... against which modern antibiotics are inactive.’

José Miguel Cisneros Herreros, Virgen del Rocío University Hospital, Spain

That’s why an EU-wide team of researchers, operating as part of an initiative known as Project Orchid, has been looking at the beta-lactam family of drugs, of which there are hundreds already on the market.

From there, they identified two which showed promise – meropenem and faropenem. As both are old products they are off-patent, meaning that if they worked in TB patients, treatment would be relatively cheap.

‘The beta-lactam family is (a) very well-known chemical class of broad spectrum antibiotics, but almost unexplored for an indication in TB,’ said Project Orchid coordinator David Barros-Aguirre, Drug Discovery Director for TB at global pharmaceutical company GlaxoSmithKline.

Mid-stage trial

The EU-funded Project Orchid, in collaboration with Professor Andreas Diacon of the TASK Applied Science research organisation, has just completed a mid-stage trial of meropenem in South Africa. The study was organised and funded in partnership with the European & Developing Countries Clinical Trials Partnership (EDCTP).

‘Its cidal (bacteria killing) profile against Mycobacterium tuberculosis and the potential to be administered safely to broad populations, including children, made us believe that further and profound investigation would be worth it,’ Barros-Aguirre added.

The results of this study will be published shortly. If this study is successful, a broader use of these beta-lactam drugs could bring a new treatment option for the millions of people across the world that are currently infected with the resistant forms of this devastating disease.

TB is not the only killer bacteria where repurposed antibiotics could be used. Another problematic infection is ventilator-associated pneumonia (VAP), a frequent and serious disease found in hospital intensive care units (ICUs).

VAP is a common and serious infection in all ICUs. But in Mediterranean countries, along with other areas where the incidence of resistant bacteria is high, this infection is often caused by multi-drug-resistant gram-negative-bacilli (MDR-GNB). These bacteria are very difficult to deal with due to the shortage of antibiotics active against them.

José Miguel Cisneros Herreros, a microbiologist at the Virgen del Rocío University Hospital in Spain, has been leading the MagicBullet project which has tested colistin – a 60-year-old antibiotic that went out of fashion in the 1970s – in treating VAP.

‘We are trying to revive an old antibiotic to treat serious infections with MDR-GNB against which modern antibiotics are inactive,’ he said.

Colistin has shown promise in lab tests against several major drug resistant bacteria and the MagicBullet team is testing it in hospitals in Greece, Italy and Spain. A total of 230 patients have been enrolled in a clinical trial and results are expected to be published next year. 

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