Current Pharmaceutical Design - Volume 10, Issue 26, 2004

There is an urgent need for new antimycobacterial drugs, and in particular for novel agents that will shorten the duration of tuberculosis chemotherapy, or overcome drug-resistant strains of the causative organism, Mycobacterium tuberculosis. Our knowledge of the tubercle bacillus and its complex interaction with the human host has improved dramatically in recent years, particularly with the determination of its co Read More

Integrated bioinformatic approaches to drug discovery exploit computational techniques to examine the flow of information from genome to structure to function. Informatics is being be used to accelerate and rationalize the process of antimycobacterial drug discovery and design, with the immediate goals to identify viable drug targets and produce a set of critically evaluated protein target models and corresponding se Read More

The antimicrobial agents used in the treatment of mycobacterial infections have remained largely unchanged for several decades. Primary treatment of tuberculosis relies on four drugs, isoniazid, a rifamycin, pyrazinamide, and ethambutol (or streptomycin), and generally results in >95% cure in uncomplicated tuberculosis infection. Drug resistance greatly complicates treatment of this disease. Treatment of tubercu Read More

New macrolides, such as clarithromycin and azithromycin, are active agents to Mycobacterium avium complex (MAC). Both clarithromycin and azithromycin are well-known for the ability to improve the prognosis of AIDS patients with disseminated MAC infection. However, the administration of monotherapy with a macrolide is usually associated with the emergence of drug resistance after a few months of use. Therefore, the Read More

Several rifamycin derivatives have been developed during the last 15 years for the treatment of mycobacterial infections. For tuberculosis, rifabutin (RFB) showed strong activity and seemed to be suitable when tuberculosis patients were also treated for their AIDS infection. Rifapentine (RPT) was evaluated in patients with or without AIDS for its intermittent use. It displayed promising activity but must be strengthened in situations, Read More

Nitroaromatic antibiotics have a long and controversial history in human and veterinary medicine. This controversy lies behind the presumption of many pharmaceutical companies that nitroaromatic compounds should be filtered from the list of drug-like compounds but stands at odds with the remarkably safe clinical record of use of such compounds. In this review, we will describe the whole-cell structure-activity relationships t Read More

Mycobacteria are intracellular pathogens that invade and reside inside macrophages. There has been a rapid resurgence in infections caused by the genus mycobacteria. Chemotherapy of mycobacterial infections is prolonged, hepatotoxic and very often inadequate in achieving optimal drug concentrations inside the cells. Recent advances in controlled delivery systems for drugs such as liposomes have sparked a renewed int Read More

The purpose of this review article is to examine the various studies that have evaluated microspheres for delivery of antimycobacterial drugs. Some of the studies strictly involve the development and evaluation of microspheres for use in antimycobacterial drug delivery, whereas others actually use drug-loaded microspheres to treat mycobacterial infections in cell lines and small animals. Although there is a potential to u Read More

Sterilizing drugs kill Mycobacterium tuberculosis that persists during chemotherapy. Predictive models should mimic the conditions causing persistence in the lesions of cavitary disease, and should grade current anti-tuberculosis drugs according to their sterilizing activity determined in clinical trials. Models should start with old, stationary cultures grown micro-aerophilically. In these, persistent bacilli occur in different po Read More

In order to cope with the worldwide increase in the prevalence of multidrug-resistant tuberculosis and Mycobacterium avium complex (MAC) infections, a number of new antimycobacterial drugs have been or are being synthesized and developed. Development of new protocols for chemotherapy of refractory mycobacterioses is also sharing promise. In this context, one promising strategy is to devise regimens to tr Read More