Explain the implications of multiple drug regimen in drug therapy.
Answers
New drugs and new regimens for the treatment of tuberculosis:
review of the drug development pipeline and implications for
national programmes
Christian Lienhardta
, Andrew Vernonb and Mario C. Raviglionec
Introduction
Current treatment of tuberculosis (TB) is based on drugs
that are more than 40 years old. Despite a demonstrated
high efficacy in clinical trials [1], standardized short-course
chemotherapy (SCC) of active drug-susceptible TB
requires direct supervision to assure good adherence and
prevent drug resistance [2]. Drugs that are active against
resistant forms of TB are less potent, more toxic, and need
to be taken for a long time (18 months). The recent
emergence of virtually untreatable extensively drug-resist-
ant TB (XDR-TB) poses a new threat to TB control
worldwide. Furthermore, effective treatment of TB in
persons coinfected with HIV is complicated due to
drug–drug interactions. Shorter and simpler regimens that
are safe, well tolerated, effective against drug-susceptible
and drug-resistant TB, appropriate for joint HIV–TB
treatment, and amenable to routine programmatic con-
ditions are needed urgently. In the present paper, we
review the problems related to current treatment of TB
and its variants, and discuss recent advances in the devel-
opment of new drugs and new regimens for the treatment
of drug-susceptible and drug-resistant TB.
The current treatment of tuberculosis
The current treatment of drug-susceptible TB is the
result of a comprehensive series of trials conducted over
20 years by the British Medical Research Council [1] that
has led to the definition of a 6-month four-drug regimen.
Treatment of drug-susceptible tuberculosis in newly
detected patients
The 6-month regimen includes rifampin, isoniazid,
pyrazinamide, and ethambutol given daily or intermit-
tently for two months, followed by rifampin and isoniazid
for four months (Table 1). Treatment-limiting side effects
vary [3], but most are not severe. Treatment regimens that
are intermittent, or use rifampin during the intensive phase
of treatment, offer some practical advantages, but their
a
Stop TB Department and Stop TB Partnership, World
Health Organization, Geneva, Switzerland, b
Clinical and
Health Systems Research Branch, Division of TB
Elimination, U.S. Centers for Disease Control and
Prevention, Atlanta Georgia, USA and c
Stop TB
Department, World Health Organization, Geneva,
Switzerland
Correspondence to Christian Lienhardt, MD, MSc, PhD,
Stop TB Department and Stop TB Partnership, World
Health Organization, Geneva, Switzerland
Tel: +41 22 791 25 86; fax: +41 22 791 48 86;
e-mail: [email protected]
Current Opinion in Pulmonary Medicine 2010,
16:186–193
Purpose of review
The aim is to review briefly the problems related to treatment of drug-susceptible and
drug-resistant tuberculosis (TB), describe recent advances in the development of new
drugs and new regimens, and discuss implications for control programmes.
Recent findings
Encouraging advances in TB drug research and development have been made since the
turn of the century, resulting in a large number of new products introduced into the
global portfolio.
Summary
Currently, nine compounds at least have advanced to clinical development, including
four existing drugs redeveloped for TB indication and five new chemical entities. Present
clinical trials are testing new combinations of drugs for a shortened treatment of drug-
susceptible TB (<6 months duration) or the safety and efficacy of new drugs in addition
to an optimized background therapy for the treatment of multidrug-resistant TB. There
are at least 34 compounds or projects in the discovery and preclinical stages, including
eight compounds in preclinical development. This increasing development of single
compounds underscores the needs for a novel approach to test for optimal drug
combinations that would be proposed for treatment of TB in all its forms, and the
necessary collaboration of pharmaceutical companies, academia, research institutions,
donors, and regulatory authorities.
Keywords
drug development, drug-resistant tuberculosis, drug-susceptible tuberculosis,