Udo Reischl

Institute of Medical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany

Received 06/18/96; Accepted 07/19/96; On-line 08/01/96

The alarming trend of coinfection of TB with HIV, has been associated with the worsening of the urban and social conditions, and changes in immigration patterns. Widespread emergence of multidrug-resistant tuberculosis (MDR-TB), especially in institutional settings, has made it difficult to control the spread of TB (20). The emergence of multidrug-resistant strains has reduced the efficacy of treatment almost to the level of the pre-antibiotic era (21). Recent MDR-TB outbreaks have been characterized by mortality rates of 50 - 80% and a duration of only 4-16 weeks from the time of diagnosis to the time of death. Resistance to rifampin, for example, involves alterations of the RNA polymerase.

With the help of specific PCR primers and sequencing of the amplified DNA, a small region within the RNA polymerase subunit ss (rpoB) gene was identified which contributes to the high-level resistance to rifampin (22). These very promising findings provide the basis for a rapid and culture-independent detection of rifampin resistance, which, at the moment, has to serve as a MDR-TB surrogate marker. The primary mechanism for emergence of the multidrug-resistance in tuberculosis is the development of different mutations in the genes that the drug targets Therefore, a continued investigation of the sites of drug interactions and the molecular basis of drug resistance at the genomic level is of utmost importance. Application of molecular biology-based technology, however, will significantly contribute to the development of rapid and reliable diagnostic protocols and, as a consequence, the production of more effective antimycobacterial drugs.

The development of resistance is unlikely to be a problem peculiar to tuberculosis. Therefore, the constant mutations in infectious pathogens which confer resistance to the host of previously effective drugs and to the immunological surveillance is a major dilemma that we continuously face (table 1).