ABSTRACT
Introduction: Tuberculosis has been and remains arguably the most important infectious disease of all time. However, when compared to other diseases of similar human impact, relatively little progress has been made. Although there are many new drugs being developed for the first time in decades, it is unclear what role each of these new drugs will play.
Areas covered: The history of current therapy is reviewed as are the challenges associated with medications currently in use. Drugs that have recently been added to the armamentarium of therapy are reviewed as well as new candidate drugs.
Expert opinion: Developing new drugs to treat tuberculosis is of critical importance but even more important is developing strategies that ensure that there is no further amplification of drug resistance around the world especially in high burden low resource settings. Directly observed therapy is the cornerstone of protecting existing and future regimens and new technologies will potentially extend the reach of monitored therapy. Challenges remain including maintaining an adequate drug supply but the greatest challenge may be the issue of persistent organisms that require prolonged therapy. By discovering the triggers of persistence and identifying new drug targets can it be possible to radically shorten therapy.
Article highlights
Current tuberculosis therapy is very effective when administered properly with an estimated cure rate of over 95% in many studies.
Despite this very high cure rate, the regimen is challenging to administer effectively given the rate of side effects, intolerance, development of drug resistance, and long duration of therapy posing challenges for programs in developed as well as developing countries alike.
Vaccine development for tuberculosis control and eventual elimination has been slow and recently concluded clinical trials of vaccine candidates have been disappointing.
Modified use of existing drugs, such as higher dose rifampin and use of quinolones as first line therapy have been recently studied but studies to date are yet to demonstrate great breakthroughs in reducing the time required for completing therapy or clearly improving cure rates over existing therapy.
Various clinical trials are underway to evaluate new combination regimens that include all new drug regimens that are not currently part of first line therapy.
Innovative ways to expand monitored therapy that incorporate technology and regulatory controls that maintain a high quality, safe drug supply will be critical moving forward to protect the efficacy of new drugs and regimens.
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Declaration of interest
M Lauzardo receives funding form the US Centers for Disease Control and Prevention for his role as the Director of the Southeastern National Tuberculosis Center at the University of Florida and for his role as site Principle Investigator for the Florida site of the TB Epidemiological Consortium (TBESC) project. M Lauzardo also receives funding from the Florida Department of Health to provide clinical services and medical consultation for the state and county TB Control Programs of Florida. C Peloquin has no conflicts of interest regarding this text, but has previously consulted for Tibotec and Otsuka. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.