US scientists from Vanderbilt University and Australian researchers from the University of New South Wales (UNSW) and the University of Western Sydney are separately sounding the alarm about the rise of tuberculosis (TB) superbugs. Although the incidence of TB has fallen in many regions, the new findings suggest serious and growing problems with TB could on the horizon. The reason? Antibiotic resistant TB superbugs are emerging that could see virtually untreatable strains of thedisease become widespread.
According to the World Health Organization (WHO), there were 9.27 million new cases of TB in 2007 and about 1.6 million TB-related deaths in 2005. Although the disease often remains latent in those who are infected, previous studies have suggested that antibiotic-resistant TB strains cause the most persistent infections. And now there is evidence of a new, persistent strain of the disease that has become resistant to the very drug previously used to treat it.
The UNSW’s Dr. Mark Tanaka and colleagues conducted a study just published in the Proceedings of the National Academy of Sciences that used epidemiological and molecular data from Mycobacterium tuberculosis strains isolated from Cuba, Estonia and Venezuela, countries where there is a high prevalence of drug-resistant TB cases. The scientists wanted to estimate the rate of evolution of TB drug resistance and to compare the relative “reproductive fitness” of resistant and drug sensitive strains.
“We found that the overall fitness of drug-resistant strains is comparable to drug-sensitive strains,” Dr. Tanaka of the UNSW Evolution and Ecology Research Centre said in a statement to the media. “This was especially so in Cuba and Estonia. The finding may reflect an inconsistency in drug treatment programs in these countries.” The scientists believe that drug-resistant strains collectively cause persistent infections, allowing the germs to evolve into more infectious strains.
“Our results imply that drug-resistant strains of TB are likely to become highly prevalent in the next few decades,” stated UNSW’s Dr Fabio Luciani, the study’s lead author, in the press statement. “They also suggest that limiting further transmission of TB might be an effective approach to reducing the impact of drug resistance.”
Another study, published in the August 15 issue of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine warns that overuse of fluoroquinolone antibiotics — which are frequently prescribed for everything from sinus infections to pneumonia — appear to be the cause of an emerging strain of fluoroquinolone-resistant TB. Ironically, these commonly used antibiotics have been considered the first-line treatment for TB strains which are resistant to other drugs.
“While fluoroquinolone resistance in TB strains has been reported since the mid 1990s, to our knowledge no one had investigated the direct causes of it. We wanted to determine whether and to what extent clinical practices were having an effect of creating that resistance,” Dr. Rose A. Devasia, clinical instructor of VanderbiltUniversity, said in a media statement.
Dr. Devasia and colleagues analyzed the records of newly diagnosed patients with culture-confirmed TB who were enrolled in Tennessee’s Medicaid program(TennCare). Using the TennCare pharmacy database, the researchers were able to find out how many of the 640 TB patients studied had been prescribed fluoroquinolone during the 12 months prior to a TB diagnosis. Then the scientists took M. tuberculosis isolates from each patient and tested to see if the TB strain causing their illness was resistant to fluoroquinolone.
Bottom line: the results showed a direct association between previous fluoroquinolone use and being infected with a strain of fluoroquinolone-resistant TB. In fact, people with TB who had used fluoroquinolones within a year of their diagnosis were about five times as likely to have a fluoroquinolone-resistant strain of TB than those who had not used these antibiotics.
What’s more, the longer the antibiotics had been taken, the more likely the TB patients were to have a fluoroquinolone-resistant strain of tuberculosis. Dr. Devasia and colleagues found that fluoroquinolone resistance was the highest among the people who took the drug more than 60 days prior to TB diagnosis. “Exposure to fluoroquinolones early in the course of disease may select for and allow a fluoroquinolone-resistant strain to predominate,” explained Dr. Devasia.
In an editorial accompanying the Vanderbilt University study, Dr. John Bernardo of Boston University School of Medicine and Wing Wei Yew of Grantham Hospital in Hong Kong warned that doctors who inappropriately prescribe antibiotics may be contributing to this growing problem of drug-resistant TB. “For now, we all need to be more careful when considering the use of these drugs in the community setting and limit the use of prolonged or repeated courses of fluoroquinolones, or even avoid them altogether, in patients who are risk of having active TB,” they wrote.
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