Use of molecular techniques to distinguish between treatment failure and exogenous reinfection with Mycobacterium tuberculosis

We investigated the means by which drug resistance emerges among drug-susceptible Mycobacterium tuberculosis strains during antituberculosis therapy. Patients who experienced failure of treatment for active pulmonary tuberculosis, who initially received diagnoses of infection with drug-susceptible M. tuberculosis, and who had had at least 3 isolates tested for drug susceptibility were selected from a 6-year period in the Estonian National Reference Laboratory archive. Eleven patients from whom 35 sequential isolates of M. tuberculosis had been obtained were recruited into the study. Their clinical data and treatment charts were analyzed and correlated with drug-susceptibility patterns and IS6110 restriction fragment-length polymorphism (RFLP) profiles. Six patients excreted isogenic drug-susceptible M. tuberculosis strains, whereas, in the other 5 patients, the isolated strain shifted from a susceptible to a resistant phenotype. In all cases, this shift correlated to a shift in RFLP pattern, which showed reinfection with a new strain. Exogenous reinfection with drug-resistant M. tuberculosis may be misinterpreted as the emergence of drug resistance if molecular testing techniques are not used.