Current development and future prospects in chemotherapy of tuberculosis.
Although treatment of drug-susceptible tuberculosis (TB) under ideal conditions may be successful in >or=95% of cases, cure rates in the field are often significantly lower due to the logistical challenges of administering and properly supervising the intake of combination chemotherapy for 6-9 months. Success rates are far worse for multidrug-resistant and extensively drug-resistant TB cases. There is general agreement that new anti-TB drugs are needed to shorten or otherwise simplify treatment for drug-susceptible and multidrug-resistant/extensively drug-resistant-TB, including TB associated with HIV infection. For the first time in over 40 years, a nascent pipeline of new anti-TB drug candidates has been assembled. Eleven candidates from seven classes are currently being evaluated in clinical trials. They include novel chemical entities belonging to entirely new classes of antibacterials, agents approved for use against infections other than TB, and an agent already approved for limited use against TB. In this article, we review the current state of TB treatment and its limitations and provide updates on the status of new drugs in clinical trials. In the conclusion, we briefly highlight ongoing efforts to discover new compounds and recent advances in alternative drug delivery systems.
Nuermberger
Eric L
EL
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231-1002, USA. enuermb@jhmi.edu
Spigelman
Melvin K
MK
Yew
Wing Wai
WW
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015780:Carbapenems / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D064687:Diarylquinolines; D016503:Drug Delivery Systems; D005029:Ethylenediamines / Q000627:therapeutic use; D024841:Fluoroquinolones / Q000627:therapeutic use; D006801:Humans; D007539:Isonicotinic Acids / Q000627:therapeutic use; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009593:Nitroimidazoles / Q000627:therapeutic use; D023303:Oxazolidinones / Q000627:therapeutic use; D010349:Patient Compliance; D011758:Pyrroles / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D012294:Rifamycins / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000995:Antitubercular Agents; D015780:Carbapenems; D064687:Diarylquinolines; D005029:Ethylenediamines; D024841:Fluoroquinolones; D007539:Isonicotinic Acids; C506841:N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine; D009593:Nitroimidazoles; D023303:Oxazolidinones; D011758:Pyrroles; D011804:Quinolines; D012294:Rifamycins; C493870:bedaquiline; D000218:Adamantane; C533848:sudoterb