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New Tuberculosis Treatment Uses Old Antibiotics in Novel Ways

OCT 20, 2016 | EINAV KEET
Despite the development of vaccines and new diagnostic tools for tuberculosis (TB), it continues to be the deadliest infectious disease in the world. While health officials continue to search for more novel tools to fight TB, a team of researchers has found that a class of antibiotics first introduced in the 1960s may offer an important weapon against the TB outbreaks of today.
The global fight against TB has offered some promising signs, with new tools to diagnose Mycobacterium tuberculosis (Mtb) infections and continued low rates of the disease in the United States and other developed countries. According to the World Health Organization (WHO) though, the worldwide prognosis is still grim, with 10.4 million individuals infected with TB and 1.8 million dying from those infections in 2015 alone. Children account for 170,000 of those deaths. India continues to be the hardest hit by the TB pandemic, followed by Indonesia, China, Nigeria, Pakistan, and South Africa. Together these countries make up 60% of TB cases, and the disease is now the biggest killer of individuals with HIV.
Multi-drug resistant TB affected about 480,000 individuals last year, says WHO, most often causing pulmonary infections. According to the Centers for Disease Control and Prevention, Mtb typically affects the lungs, causing symptoms such as prolonged cough, chest pain, coughing up of blood or phlegm, fatigue, weight loss, fever, and night sweats.
TB infections can occur in any part of the body though, such as the kidney, spine, and brain. Individuals who have TB bacteria in their body but no symptoms of illness have what is called latent TB infection, and still must receive treatment to prevent the onset of disease. TB disease from active and multiplying bacteria can take several months to treat, and up to 24 months for individuals with highly antibiotic-resistant strains of the disease. Individuals with weakened immune systems–such as those with HIV–are at higher risk of developing the active disease.

A recent study, published in the Nature journal, Scientific Reports, tackled the issue of treating today’s contained but virulent TB pandemic. “When it comes to infectious diseases, in our global society we cannot limit our vision to developing and developed world since diseases know no boundaries,” study author Santiago Ramón-García told Contagion. “It is true that there is a misconception in developed societies regarding the real extension of the TB pandemic. However, TB is the most-deadly infectious disease worldwide.” The study authors focused on the issue of lacking new antibiotic drugs and decades-old treatment guidelines for TB, and the continued reliance on the antibiotic rifampicin for these infections. The authors screened commercially available antibiotics, finding that beta-lactam first generation cephalosporins are highly synergistic with rifampicin, and studied how cephalosporins work alone and also paired with other drugs to fight various Mtb strains. In vitro testing found that cephalosporins work well against multiple strains of tuberculosis. When these beta-lactams were not as effective individually, they had high intercellular synergy with rifampicin, becoming more active together and more bactericidal and sterilizing with interaction. Cephalosporins were not as synergistic with rifabutin, another drug in rifamycin group.

Big advances in treatment can