Comparison of fitness of two isolates of Mycobacterium tuberculosis, one of which had developed multi-drug resistance during the course of treatment

Objectives: We report the cases of two patients, brother and sister, both w ith pulmonary tuberculosis, Both patients complied poorly with treatment, O ne developed multi-drug resistant disease, whilst the other did not. We aim ed to show that the two infecting strains were the same, and then to compar e the fitness of the resistant strain to that of the sensitive strain. Methods: The isolates were typed by RFLP, The fitness of the multi-drug res istant tuberculosis strain was determined by calculating the ratio of gener ation produced by the drug-resistant and a drug-susceptible strain in a mix ed culture. The number of bacteria present in this broth culture was estima ted using the Miles and Misra technique, The number of drug-resistant bacte ria present was determined by inoculating aliquots of broth onto Middlebroo k 7H10 agar with 5 mg/l rifampicin, Results: The infecting strain of Mycobacterium tuberculosis was shown to be the same on RFLP typing in both cases. It was found that the multi-drug re sistant organism had decreased fitness compared to the sensitive organism. Conclusion: The decreased relative fitness of the resistant strain implies a physiological cost for the development of drug resistance, (C) 2000 The B ritish Infection Society.