The Cochrane Infectious Diseases Group (link is external) (CIDG), which has its editorial base at LSTM, helps prepare systematic reviews related to the diagnosis and treatment of tuberculosis. Ahead of World TB Day, this week welcomes the publication of a Special Collection on the Cochrane Library (link is external) that tracks the development of exciting new diagnostic tests for tuberculosis and provides a narrative over the last 10 years of how systematic reviews, many of them Cochrane Reviews, have helped informed investment in diagnostics in low- and middle-income countries. The CIDG has also published a Cochrane Review – on linezolid, a drug that has been allocated an increasingly prominent role in the treatment of drug-resistant tuberculosis, underlining the difficulties facing patients with drug-resistant disease; in that potential benefits in cure rates must be balanced against the downside of considerable side effects.
Special Collection on diagnosing tuberculosis
New ways of testing whether people have tuberculosis have revolutionised detection and treatment. In 2010, the World Health Organization (WHO) recommended the use of a diagnostic test called Xpert®, and since then this test has been evaluated in different populations and settings, and new products have come on to the market. This Special Collection provides a description of the key reviews and global guidelines associated with each developed by the WHO. The collection covers tests for early detection of the disease, tests for drug resistance, tests in people with HIV, tests in children, and tests for latent tuberculosis infection.
Karen Steingart, honorary researcher at the LSTM, said, “Accessible diagnostics are critical for ensuring that people are started on appropriate treatment. Based on the evidence, WHO-recommended rapid tests should be replacing microscopy as the initial diagnostic test for tuberculosis.”
Steingart K, Gilpin C, Kohli M, Garner P. Cochrane Special Collections. Diagnosing tuberculosis. Cochrane Database of Systematic Reviews 2019, Issue 3. DOI: SC000034. (link is external)
Tuberculosis drug resistance is a worldwide problem, and linezolid is a drug that may help people with multi-drug resistant disease. The problem is that we still lack high quality information on this form of the disease. All of the drugs have side-effects, which makes it difficult for patients to take them and means that the drugs are more likely to be harmful. Clinicians and patients need fair and independent summaries of the balance between the benefits and harms of these drugs.
Bhagteshwar Singh and his colleagues summarised the evidence from published studies in this recent Cochrane Review. Whilst there are already several reviews in existence, this Cochrane Review was conducted independently to try and summarise the potential advantages in terms of cure, and the associated side effects.
The review authors’ data were limited, with 104 participants recruited in two trials. One trial reported a higher rate of cure and lower risk of treatment failure when linezolid was added to conventional treatment, though the review authors had very low certainty in the reported benefit. The other suggested that linezolid causes faster clearance of tuberculosis bacteria from sputum. Harmful effects were common, with about one-fifth of people across 11 other studies having to discontinue linezolid. Reporting of safety and tolerability by studies was poor, preventing a meaningful summary of these important outcomes.
The review helps illustrate the difficulties facing patients with drug-resistant disease, and the limited research in evaluating these new drugs, especially in lower income countries.
Dr Singh noted, “This is now one of WHO’s core drugs to treat drug-resistant tuberculosis, but we need to be aware of the limited data available, especially on its toxicity. This review helps to highlight the gaps in our knowledge, equip clinicians for informed discussions with patients, and provide policy-makers with an overview for difficult decisions”.
Singh B, Cocker D, Ryan H, Sloan DJ. Linezolid for drug‐resistant pulmonary tuberculosis. (link is external)Cochrane Database of Systematic Reviews 2019, Issue 3. Art. No.: CD012836. DOI:10.1002/14651858.CD012836.pub2.